An ultrasound-based comparative study on carotid plaques in HIV-positive patients vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory lesions?

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Maggi, Paolo; Perilli, Francesco; Lillo, Antonio; Carito, Valentina; Epifani, Giuseppe; Bellacosa, Chiara; Pastore, Giuseppe; Regina, Guido

2007-02-01

We have previously described two cases of HIV-1-positive patients undergoing surgery for stenosis of the internal carotid arteries. Histology revealed an extensive inflammatory infiltration of the vascular wall and no evidence of atheromasic plaque. This unexpected pattern of carotid damage prompted us to perform a more accurate investigation of the characteristics of carotid plaques in a group of HIV-positive patients. The results were compared with those obtained from young patients affected by atherosclerosis of the epi-aortic vessels and patients with arteritis. The patients underwent ultrasonography of the epi-aortic vessels using one of the latest generation power color-Doppler with 7.5 MHz probes. The study population included 61 HIV-positive patients and 47 HIV-negative patients (37 atherosclerotic and 10 with arteritis). Compared with HIV-negative atherosclerotic patients, there were significantly higher proportions of HIV-positive patients with iso-hypoechogenic lesions (81.8 vs. 29%) that were homogeneous both in their parietal and endoluminal portions (96.7 vs. 21.6% and 88.5 vs. 54.0%, respectively), with a smooth or slightly irregular surface (99.0 vs. 56.7%) (P=0.001 for all differences). No statistically significant differences were seen between HIV-positive and arteritis patients. Our study evidenced that the ultrasonographic structure of the epi-aortic lesions in HIV-positive patients substantially differ from those of the plaques in atherosclerotic patients, although they share similar characteristics with patients affected by arteritis. Further investigations are warranted to better define the structure and the mechanism of onset of these lesions.

The formation of atherosclerotic plaque, its destabilisation and diagnostics

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Piotr Kaźmierski

2014-04-01

Full Text Available According to the established medical knowledge, the atheromatous lesions occur in the arteries of large and medium diameter. Their presence in the aorta, arteries of extremities as well as extracerebral and coronal arteries is clinically relevant. The evolution of atherosclerotic plaques probably starts in the prenatal development, what may be proved by the presence of the fatty streaks in endothelium of coronal arteries in some newborns. Then it evolves through lipid accumulation, media inflammatory response, vasa vasorum proliferation, fibrination and calcification of plaques. Researches proved that the matter of atherosclerosis is exaggerated inflammatory proliferative reaction to the arterial wall damage. The oxidative stress phenomenon and infections with common pathogens play an undoubtful role in this process. Ultimately the direct damage is an effect of immune response cells infiltration and secretion of cytokines and proinflammatory factors. Among the cells of immune system responsible for formation and development of atheromatous plaque are considered: macrophages, dendritic cells, T and B lymphocytes, monocytes. Attention was also paid to the inflammatory mediators and growth factors. Scientist are interested in unstable atherosclerotic plaque and accompanying inflammatory process within the artery wall for a long time. Meanwhile, there are conducted researches on inflammation markers underlying the destabilisation of plaques. Revealing the role of these cells in evolution of atherosclerosis would enable more complex understanding of the mechanism of lesions development. Then it would facilitate an introduction of the new and upgraded methods of treatment and prevention. Also the progress of imaging examinations is meaningful for diagnostics and treatment. It is contributory to the choice of therapeutic strategy and assessment of surgical intervention urgency. In the clinical practice there are recognized standards of imaging the

SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice.

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Zheng, Lingyun; Wu, Teng; Zeng, Cuiling; Li, Xiangli; Li, Xiaoqiang; Wen, Dingwen; Ji, Tianxing; Lan, Tian; Xing, Liying; Li, Jiangchao; He, Xiaodong; Wang, Lijing

2016-01-01

Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression. we generated apoE(-/-); SAP(-/-) (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development. SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE(-/-) mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE(-/-) mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages. SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE(-/-) mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

International Nuclear Information System (INIS)

Guo Yanhong; Chen Kuanghueih; Gao Wei; Li Qian; Chen Li; Wang Guisong; Tang Jian

2007-01-01

Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE -/- mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury

The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II-induced atherosclerosis in mice

DEFF Research Database (Denmark)

Wintmo, P.; Johansen, S. H.; Hansen, P. B. L.

2017-01-01

Aim: The water channel aquaporin 1 (AQP1) promotes endothelial cell migration. It was hypothesized that AQP1 promotes neovascularization and growth of atherosclerotic plaques. Methods: AQP1 immunoreactivity and protein abundance was examined in human and murine atherosclerotic lesions and aortic...... minipumps for 4 weeks. Results: In human atherosclerotic lesions and AAA, AQP1 immunoreactive protein was associated with intralesional small vessels. In ApoE-/- mouse aorta, APQ1 mRNA levels were increased with time on WD (n = 7-9, P ... increased with time on WD but was not different between ApoE-/- and AQP1-/-ApoE-/- mice at either 8 or 16 weeks (n = 13-15). Baseline blood pressure and ANGII-induced hypertension were not different between genotypes. Conclusion: AQP1 is expressed in atherosclerotic lesion neovasculature in human and mouse...

Myocardial perfusion scintigraphy fi ndings in patients with mild coronary atherosclerotic lesions on coronary angiography

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Zeki Dostbil

2010-09-01

Full Text Available Objectives: Myocardial perfusion scintigraphy (MPS iswidely used in functional assessment of myocardial per-fusion. But, some study results are in contradiction withseverity of coronary artery disease detected by coronaryangiography (CA. It is frequently encountered case thatCA is completely normal whereas MPS describes isch-emia. In this study, we aimed to investigate whether mildatherosclerotic lesions cause ischemia.Materials and methods: MPS with 99mTc-MIBI was per-formed in 52 patients who applied to cardiology clinics forhistory of chest pain and underwent diagnostic CA within3 months.Results: In 22 of 52 patients with mild atherosclerotic le-sions, ischemia in various degrees was detected on MPS.In statistical analysis, any signifi cant relationship was notfound between ischemia and gender, hypertension, DM,dyslipidemia, smoking, mitral valve insuffi ciency, left ven-tricular hypertrophy, exercise testing result and affectedcoronary artery.Conclusion: Our study fi ndings have shown that mild ath-erosclerotic lesions even at very early stage may causemyocardial ischemia

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice.

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van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-05-01

Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages. Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. © 2015 The British Pharmacological Society.

Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins.

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Zhang, Wenli; He, Hongliang; Liu, Jianping; Wang, Ji; Zhang, Suyang; Zhang, Shuangshuang; Wu, Zimei

2013-01-01

High density lipoproteins (HDL) have been successfully reconstructed to deliver a large number of lipophilic drugs. Here, discoidal and spherical recombinant HDL loaded with cardiovascular drug tanshinone IIA (TA) were constructed (TA-d-rHDL and TA-s-rHDL), respectively. And next their in vitro physiochemical and biomimetic properties were characterized. Furthermore, pharmacokinetics, atherosclerotic lesions targeting effects and antiatherogenic efficacies were elaborately performed and compared in atherosclerotic New Zealand White (NZW) rabbits. In vitro characterizations results showed that both TA-d-rHDL and TA-s-rHDL had nano-size diameter, high entrapment efficiency (EE) and drug-loading capacity (DL). Additionally, similar to their native counterparts, TA-d-rHDL maintained remodeling behaviors induced by lecithin cholesterol acyltransferase (LCAT), and TA leaked during remodeling behaviors. Pharmacokinetic studies manifested that both TA-d-rHDL and TA-s-rHDL markedly improved pharmacokinetic behaviors of TA in vivo. Ex vivo imaging demonstrated that both d-rHDL and s-rHDL bound more avidly to atherosclerotic lesions than to normal vessel walls, and s-rHDL had better targeting effect than d-rHDL. Pharmacodynamic tests illustrated that both TA-d-rHDL and TA-s-rHDL had much stronger antiatherogenic efficacies than conventional TA nanostructured lipid carriers (TA-NLC), TA liposomes (TA-L) and commercially available preparation Sulfotanshinone Sodium Injection (SSI). Moreover, TA-s-rHDL had more potent antiatherogenic efficacies than TA-d-rHDL. Collectively our studies indicated that rHDL could be exploited as potential delivery vehicles of TA targeting atherosclerotic lesions as well as synergistically improving efficacies, especially for s-rHDL. Copyright © 2012 Elsevier Ltd. All rights reserved.

Macrophage p53 controls macrophage death in atherosclerotic lesions of apolipoprotein E deficient mice

NARCIS (Netherlands)

Boesten, L.S.M.; Zadelaar, A.S.M.; Nieuwkoop, A. van; Hu, L.; Teunisse, A.F.A.S.; Jochemsen, A.G.; Evers, B.; Water, B. van de; Gijbels, M.J.J.; Vlijmen, B.J.M. van; Havekes, L.M.; Winther, M.P.J. de

2009-01-01

The cellular composition of atherosclerotic lesions is determined by many factors including cell infiltration, proliferation and cell death. Tumor suppressor gene p53 has been shown to regulate both cell proliferation and cell death in many cell types. In the present study, we investigated the role

Arterial 18F-fluorodeoxyglucose uptake reflects balloon catheter-induced thrombus formation and tissue factor expression via nuclear factor-κB in rabbit atherosclerotic lesions

International Nuclear Information System (INIS)

Yamashita, Atsushi; Zhao, Yan; Zhao, Songji

2013-01-01

Imaging modalities to assess atherosclerotic plaque thrombogenicity have not been established, so in this study the relationship between [ 18 F]-fluorodeoxyglucose ( 18 F-FDG) uptake and thrombus formation was investigated in rabbit atherosclerotic arteries. Atherosclerotic plaque was induced in the iliacofemoral artery by balloon injury and a 0.5% cholesterol diet. At 3 weeks after the first balloon injury, the arteries were visualized by 18 F-FDG positron emission tomography (PET) imaging 2 h after an 18 F-FDG infusion, and then arterial thrombus was induced by a second balloon injury of both iliacofemoral arteries. Imaging with 18 F-FDG-PET revealed significantly more radioactivity along the injured (0.63±0.12 standardized uptake value (SUV)max), than the contralateral non-injured artery (0.34±0.08 SUVmax, n=17, P 18 F-FDG uptake reflects the thrombogenicity of atherosclerotic plaque following balloon injury. (author)

Bilirubin Prevents Atherosclerotic Lesion Formation in Low-Density Lipoprotein Receptor-Deficient Mice by Inhibiting Endothelial VCAM-1 and ICAM-1 Signaling.

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Vogel, Megan E; Idelman, Gila; Konaniah, Eddy S; Zucker, Stephen D

2017-04-01

Numerous epidemiological studies support an inverse association between serum bilirubin levels and the incidence of cardiovascular disease; however, the mechanism(s) by which bilirubin may protect against atherosclerosis is undefined. The goals of the present investigations were to assess the ability of bilirubin to prevent atherosclerotic plaque formation in low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice and elucidate the molecular processes underlying this effect. Bilirubin, at physiological concentrations (≤20 μmol/L), dose-dependently inhibits THP-1 monocyte migration across tumor necrosis factor α-activated human umbilical vein endothelial cell monolayers without altering leukocyte binding or cytokine production. A potent antioxidant, bilirubin effectively blocks the generation of cellular reactive oxygen species induced by the cross-linking of endothelial vascular cell adhesion molecule 1 (VCAM-1) or intercellular adhesion molecule 1 (ICAM-1). These findings were validated by treating cells with blocking antibodies or with specific inhibitors of VCAM-1 and ICAM-1 signaling. When administered to Ldlr -/- mice on a Western diet, bilirubin (30 mg/kg intraperitoneally) prevents atherosclerotic plaque formation, but does not alter circulating cholesterol or chemokine levels. Aortic roots from bilirubin-treated animals exhibit reduced lipid and collagen deposition, decreased infiltration of monocytes and lymphocytes, fewer smooth muscle cells, and diminished levels of chlorotyrosine and nitrotyrosine, without changes in VCAM-1 or ICAM-1 expression. Bilirubin suppresses atherosclerotic plaque formation in Ldlr -/- mice by disrupting endothelial VCAM-1- and ICAM-1-mediated leukocyte migration through the scavenging of reactive oxygen species signaling intermediaries. These findings suggest a potential mechanism for the apparent cardioprotective effects of bilirubin. © 2017 The Authors. Published on behalf of the American Heart Association, Inc

Identification of periodontal pathogens in atherosclerotic vessels

DEFF Research Database (Denmark)

Fiehn, Nils-Erik; Larsen, Tove; Christiansen, Natalia

2005-01-01

Epidemiological studies have shown that periodontitis may be associated with presence of atherosclerosis. DNA from periodontal pathogens has been detected in atherosclerotic lesions, but viable oral bacteria have not yet been isolated from atherosclerotic plaques. The purpose of the present study...... was to determine if viable oral bacteria could be isolated from atherosclerotic lesions and if DNA from periodontal pathogens could be detected by use of polymerase chain reaction (PCR) techniques....

Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

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Rosa Sessa

2013-07-01

Full Text Available Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development.

Experimental study of 99Tcm-Ap4A in detection of atherosclerotic plaques

International Nuclear Information System (INIS)

Cao Wei; Zhang Yongxue; An Rui

2001-01-01

Objective: To study 99 Tc m labelled di-adenosine tetraphosphate (Ap4A), a compound can bind on P 2 purine receptors on atherosclerotic lesions, for imaging experimental atherosclerotic plaques in New Zealand White (NZW) rabbits. Methods: Twenty male NZW rabbits were submitted immune-injury and fed with high cholesterol diet for more than 2 months. To label the 99 Tc m to Ap4A, stannous tartrate solution was used. 99 Tc m -Ap4A was purified on a Sephadex G-25 column and tested for radiochemistry purity on thin layer chromatography. A biodistribution study was carried out on KM mice. Thirty minutes after intravenous injection of 7.4 MBq 99 Tc m -Ap4A, 5 normal NZW rabbits and 5 NZW rabbits with atherosclerotic lesions were sacrificed; their abdominal aortas were removed and covered with X-ray films. Exposed for 24 h in refrigerator, the films were developed and fixed. In another 5 NZW rabbits with atherosclerotic lesions, blood samples, atherosclerotic plaques and normal aortic wall samples were removed. Lesion to blood (target/blood, T/B), lesion to normal (target/non-target, T/NT) radioactivity ratios were calculated. 74 MBq 99 Tc m -Ap4A was injected into marginal ear veins of 5 atherosclerotic and 5 normal NZW rabbits. Simultaneously in vivo images were recorded for more than 4 h. In another group, 30 min after 99 Tc m -Ap4A administration, the animals were sacrificed and their abdominal aortas were removed. The abdominal aortas were placed on the face of SPECT and images acquisition was performed. Results: The radiochemistry purity of 99 Tc m -Ap4A was 85% to 91%. Biodistribution study revealed the clearance of 99 Tc m -Ap4A from blood was rapid. Thirty min after 99 Tc m -Ap4A administration, T/B radio was 3.17 +- 1.27, T/NT ratio was 5.23 +- 1.87. On the radioautography film shadows of atherosclerotic plaques were clearly visible. The atherosclerotic plaques on the aorta samples also can be seen on ex vivo images. Atherosclerotic abdominal aortas and lesions

P2Y6 receptor potentiates pro-inflammatory responses in macrophages and exhibits differential roles in atherosclerotic lesion development.

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Ricardo A Garcia

Full Text Available BACKGROUND: P2Y(6, a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y(6 deficiency on atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Cell-based studies in 1321N1 astrocytoma cells, which lack functional P2Y(6 receptors, showed that exogenous expression of P2Y(6 induces a robust, receptor- and agonist-dependent secretion of inflammatory mediators IL-8, IL-6, MCP-1 and GRO1. P2Y(6-mediated inflammatory responses were also observed, albeit to a lesser extent, in macrophages endogenously expressing P2Y(6 and in acute peritonitis models of inflammation. To evaluate the role of P2Y(6 in atherosclerotic lesion development, we used P2Y(6-deficient mice in three mouse models of atherosclerosis. A 43% reduction in aortic arch plaque was observed in high fat-fed LDLR knockout mice lacking P2Y(6 receptors in bone marrow-derived cells. In contrast, no effect on lesion development was observed in fat-fed whole body P2Y(6xLDLR double knockout mice. Interestingly, in a model of enhanced vascular inflammation using angiotensin II, P2Y(6 deficiency enhanced formation of aneurysms and exhibited a trend towards increased atherosclerosis in the aorta of LDLR knockout mice. CONCLUSIONS: P2Y(6 receptor augments pro-inflammatory responses in macrophages and exhibits a pro-atherogenic role in hematopoietic cells. However, the overall impact of whole body P2Y(6 deficiency on atherosclerosis appears to be modest and could reflect additional roles of P2Y(6 in vascular disease pathophysiologies, such as aneurysm formation.

Atherosclerotic stenoses of renal arteries: Evaluation with CT

International Nuclear Information System (INIS)

Marteau, V.; Melki, J.P.; DuTemple, C.; Despres, E.; Taieb, A.

1987-01-01

Recent reports have shown that the long-term results of transluminal angioplasty (PTA) in renal arteries, performed to treat renovascular hypertension resulting from atherosclerotic disease, depended on the location, extent, and consistency of the obstructing lesions. Therefore, 30 patients shown with arteriography to have 40 atherosclerotic stenoses and five occlusions of the renal artery underwent CT for study of the walls of the aorta and renal arteries. CT easily demonstrates atherosclerotic lesions and seems better than arteriography when the lesions are ostial. It shows whether stenoses are calcified and also defines the lesions of the abdominal aorta, which is helpful when surgical bypass is considered. The paper presents the authors' preliminary findings. Long-term follow-up of these patients show if CT has a predictive value about PTA results

Molecular imaging of atherosclerotic plaques with technetium-99m-labelled antisense oligonucleotides

International Nuclear Information System (INIS)

Qin Guangming; Zhang Yongxue; Cao Wei; An Rui; Gao Zairong; Xu Wendai; Zhang Kaijun; Li Guiling; Li Shuren

2005-01-01

The purpose of this study was to visualise experimental atherosclerotic lesions using radiolabelled antisense oligonucleotides (ASONs). Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for approximately 60 days. In vivo and ex vivo imaging was performed in atherosclerotic rabbits and normal control rabbits after i.v. injection of 92.5±18.5 MBq 99m Tc-labelled ASON or 99m Tc-labelled sense oligonucleotides. Immediately after the in vivo imaging, the animals were sacrificed and ex vivo imaging of the aortic specimens was performed. Biodistribution of radiolabelled c-mycASON was evaluated in vivo in atherosclerotic rabbits. Planar imaging revealed accumulation of 99m Tc-labelled c-mycASON in atherosclerotic lesions along the artery wall. Ex vivo imaging further demonstrated that the area of activity accumulation matched the area of atherosclerotic lesions. In contrast, no atherosclerotic lesions were found in the vessel wall and no positive imaging results were obtained in animals of the control group. This molecular imaging approach has potential for non-invasive imaging of atherosclerotic plaques at an early stage. (orig.)

Panax Notoginseng Saponins Promote Endothelial Progenitor Cell Mobilization and Attenuate Atherosclerotic Lesions in Apolipoprotein E Knockout Mice

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Ya Liu

2013-09-01

Full Text Available Background: Endothelial progenitor cells (EPCs derived from the bone marrow (BM play a key role in the homeostasis of vascular repair by enhanced reendothelialization. Panax notoginseng saponins (PNS, a highly valued traditional Chinese medicine, has been shown to reduce morbidity and mortality from coronary artery disease. The present research was designed to explore the contribution of progenitor cells to the progression of atherosclerotic plaques and the possible modulatory role of PNS in this process. Methods: PNS (60 or 120 mg/kg via intraperitoneal injection was administered over 8 weeks in apolipoprotein E knockout mice on an atherogenic diet. The sizes and histochemical alteration of atherosclerotic lesions and numbers of EPCs in BM and peripheral blood were analyzed. The expression of chemokine stromal cell-derived factor 1α (SDF-1α and its receptor, CXCR4, was monitored as well. Results: PNS significantly reduced the lesion area and intima-to-media ratio compared to vehicle treatment. PNS also augmented endothelialization and reduced the smooth muscle cell (SMCs content of the lesions. The number of c-kit and sca-1 double-positive progenitor cells and flk-1 and sca-1 double-positive progenitor cells were significantly increased in the BM and the peripheral blood of the PNS-treated groups. PNS treatment increased the plasma levels of SDF-1α and SCF as well as the BM levels of matrix metalloproteinase-9 (MMP-9. Moreover, the mRNA levels of SDF-1α and protein levels of CXCR4 were both increased in the BM of mice treated with PNS, while SDF-1α expression decreased. Conclusion: PNS reduce the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilization. SDF-1α-CXCR4 interactions and the possible modulatory role of PNS in this process may contribute to the increased progenitor cell mobilization.

The Protective Effect of Apamin on LPS/Fat-Induced Atherosclerotic Mice

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Soo-Jung Kim

2012-01-01

Full Text Available Apamin, a peptide component of bee venom (BV, has anti-inflammatory properties. However, the molecular mechanisms by which apamin prevents atherosclerosis are not fully understood. We examined the effect of apamin on atherosclerotic mice. Atherosclerotic mice received intraperitoneal (ip injections of lipopolysaccharide (LPS, 2 mg/kg to induce atherosclerotic change and were fed an atherogenic diet for 12 weeks. Apamin (0.05 mg/kg was administered by ip injection. LPS-induced THP-1-derived macrophage inflammation treated with apamin reduced expression of tumor necrosis factor (TNF-α, vascular cell adhesion molecule (VCAM-1, and intracellular cell adhesion molecule (ICAM-1, as well as the nuclear factor kappa B (NF-κB signaling pathway. Apamin decreased the formation of atherosclerotic lesions as assessed by hematoxylin and elastic staining. Treatment with apamin reduced lipids, Ca2+ levels, and TNF-α in the serum from atherosclerotic mice. Further, apamin significantly attenuated expression of VCAM-1, ICAM-1, TGF-β1, and fibronectin in the descending aorta from atherosclerotic mice. These results indicate that apamin plays an important role in monocyte/macrophage inflammatory processing and may be of potential value for preventing atherosclerosis.

Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles

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Qin J

2014-12-01

Full Text Available Jinbao Qin,1,* Chen Peng,2,* Binghui Zhao,2,* Kaichuang Ye,1 Fukang Yuan,1 Zhiyou Peng,1 Xinrui Yang,1 Lijia Huang,1 Mier Jiang,1 Qinghua Zhao,3 Guangyu Tang,2 Xinwu Lu1,4 1Department of Vascular Surgery, Shanghai Ninth People’s Hospital Affiliated to Shanghai JiaoTong University, School of Medicine; 2Department of Radiology, Shanghai Tenth People’s Hospital Affiliated to Tongji University, School of Medicine; 3Department of Orthopaedics, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University; 4Vascular Center of Shanghai JiaoTong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS. Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs with polyethylene glycol (PEG and fluorescein isothiocyanate (FI coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 µM and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases. Keywords: atherosclerosis, CT, in vivo

Evaluation of atherosclerotic lesions using dextran- and mannan–dextran-coated USPIO: MRI analysis and pathological findings

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Mukaisho K

2012-05-01

Full Text Available Keiko Tsuchiya1, Norihisa Nitta1, Akinaga Sonoda1, Ayumi Nitta-Seko1, Shinichi Ohta1, Masashi Takahashi1, Kiyoshi Murata1, Kenichi Mukaisho2, Masashi Shiomi3, Yasuhiko Tabata4, Satoshi Nohara51Department of Radiology, 2Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, 3Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Hyogo, 4Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 5Nagoya Research Laboratory, Meito Sangyo, Kiyosu, Aichi, JapanAbstract: Magnetic resonance imaging (MRI can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic iron oxides (USPIO. Positing that improved USPIO with a higher affinity for atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of dextran- and mannan–dextran-coated USPIO (D-USPIO and DM-USPIO, respectively by the atherosclerotic walls of rabbits. We intravenously injected atherosclerotic rabbits with DM-USPIO (n = 5 or D-USPIO (n = 5. Two rabbits were the controls. The doses delivered were 0.08 (dose 1 (n = 1, 0.4 (dose 2 (n = 1, or 0.8 (dose 3 (n = 3 mmol iron/Kg. The dose 3 rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA before and 5 days after USPIO administration. Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR of the aortic wall in the same region of interest (ROI was calculated in both in vivo and in vitro studies. Histological assessment through measurement of iron-positive regions in Prussian blue-stained specimens showed that iron-positive regions were significantly larger in rabbits injected with DM- rather than D-USPIO (P < 0.05 for all doses. In vivo MRA showed that the SNR-reducing effect of DM- was greater than that of D-USPIO (P < 0.05. With in vitro MRI scans, SNR was significantly

Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.

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Helene Hartwig

Full Text Available Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.

Rationale, Design, and Methodological Aspects of the BUDAPEST-GLOBAL Study (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions).

Science.gov (United States)

Maurovich-Horvat, Pál; Tárnoki, Dávid L; Tárnoki, Ádám D; Horváth, Tamás; Jermendy, Ádám L; Kolossváry, Márton; Szilveszter, Bálint; Voros, Viktor; Kovács, Attila; Molnár, Andrea Á; Littvay, Levente; Lamb, Hildo J; Voros, Szilard; Jermendy, György; Merkely, Béla

2015-12-01

The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST-GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single-center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same-sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non-contrast-enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non-contrast-enhanced image slice was acquired at the level of L3-L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3-dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per-patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST-GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders. © 2015 Wiley Periodicals, Inc.

Salusins: Potential Use as a Biomarker for Atherosclerotic Cardiovascular Diseases

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Kengo Sato

2013-01-01

Full Text Available Human salusin-α and salusin-β are related peptides produced from prosalusin. Bolus injection of salusin-β into rats induces more profound hypotension and bradycardia than salusin-α. Central administration of salusin-β increases blood pressure via release of norepinephrine and arginine-vasopressin. Circulating levels of salusin-α and salusin-β are lower in patients with essential hypertension. Salusin-β exerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs and fibroblasts than salusin-α. Salusin-β accelerates inflammatory responses in human endothelial cells and monocyte-endothelial adhesion. Human macrophage foam cell formation is stimulated by salusin-β but suppressed by salusin-α. Chronic salusin-β infusion into apolipoprotein E-deficient mice enhances atherosclerotic lesions; salusin-α infusion reduces lesions. Salusin-β is expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-α and salusin-β immunoreactivity have been detected in human coronary atherosclerotic plaques, with dominance of salusin-β in macrophage foam cells, VSMCs, and fibroblasts. Circulating salusin-β levels increase and salusin-α levels decrease in patients with coronary artery disease. These findings suggest that salusin-β and salusin-α may contribute to proatherogenesis and antiatherogenesis, respectively. Increased salusin-β and/or decreased salusin-α levels in circulating blood and vascular tissue are closely linked with atherosclerosis. Salusin-α and salusin-β could be candidate biomarkers and therapeutic targets for atherosclerotic cardiovascular diseases.

Atherosclerotic Plaque Characteristics by CT Angiography Identify Coronary Lesions That Cause Ischemia: a Direct Comparison to Fractional Flow Reserve

Science.gov (United States)

Park, Hyung-Bok; Heo, Ran; Hartaigh, Bríain ó; Cho, Iksung; Gransar, Heidi; Nakazato, Ryo; Leipsic, Jonathon; Mancini, G.B. John; Koo, Bon-Kwon; Otake, Hiromasa; Budoff, Matthew J.; Berman, Daniel S.; Erglis, Andrejs; Chang, Hyuk-Jae; Min, James K.

2014-01-01

Objective We evaluated the association between atherosclerotic plaque characteristics (APCs) by coronary CT angiography (CT) and lesion ischemia by fractional flow reserve (FFR). Background FFR is the gold standard for determining lesion ischemia. While APCs by CT—including aggregate plaque volume % (%APV), positive remodeling (PR), low attenuation plaque (LAP) and spotty calcification (SC)—are associated with future coronary syndromes, their relationship to lesion ischemia is unclear. Methods 252 patients (17 centers, 5 countries) [mean age 63 years, 71% males] underwent CT, with FFR performed for 407 coronary lesions. CT was interpreted for 50% stenosis, with the latter considered obstructive. APCs by CT were defined as: (1) PR, lesion diameter/reference diameter >1.10; (2) LAP, any voxel 50% but not for 50%. PMID:25592691

[18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs.

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Miikka Tarkia

Full Text Available Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model.First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days in farm pigs (n = 10. After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33 were harvested for ex vivo measurement of radioactivity and autoradiography (ARG.Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively. Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04. In vivo PET imaging showed the highest target-to-background ratio (TBR of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5 and either intimal thickening (1.2±0.4, P = 1.0 or atheroma (1.6±0.6, P = 0.4.We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.

Numerical investigation and identification of susceptible sites of atherosclerotic lesion formation in a complete coronary artery bypass model.

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Zhang, Jun-Mei; Chua, Leok Poh; Ghista, Dhanjoo N; Yu, Simon Ching Man; Tan, Yong Seng

2008-07-01

As hemodynamics is widely believed to correlate with anastomotic stenosis in coronary bypass surgery, this paper investigates the flow characteristics and distributions of the hemodynamic parameters (HPs) in a coronary bypass model (which includes both proximal and distal anastomoses), under physiological flow conditions. Disturbed flows (flow separation/reattachment, vertical and secondary flows) as well as regions of high oscillatory shear index (OSI) with low wall shear stress (WSS), i.e., high-OSI-and-low-WSS and low-OSI-and-high-WSS were found in the proximal and distal anastomoses, especially at the toe and heel regions of distal anastomosis, which indicate highly suspected sites for the onset of the atherosclerotic lesions. The flow patterns found in the graft and distal anastomoses of our model at deceleration phases are different from those of the isolated distal anastomosis model. In addition, a huge significant difference in segmental averages of HPs was found between the distal and proximal anastomoses. These findings further suggest that intimal hyperplasia would be more prone to form in the distal anastomosis than in the proximal anastomosis, particularly along the suture line at the toe and heel of distal anastomosis.

Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

Science.gov (United States)

2014-01-01

Background The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. Methods A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. Results After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. Conclusions The prevalence and risk of lower limb

How to manage hypertension with atherosclerotic renal artery stenosis?

Science.gov (United States)

Ricco, Jean-Baptiste; Belmonte, Romain; Illuminati, Guilio; Barral, Xavier; Schneider, Fabrice; Chavent, Bertrand

2017-04-01

The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

Electrical impedance of layered atherosclerotic plaques on human aortas

NARCIS (Netherlands)

C.J. Slager (Cornelis); A.C. Phaff; C.E. Essed; N. Bom (Klaas); J.C.H. Schuurbiers (Johan); P.W.J.C. Serruys (Patrick)

1992-01-01

textabstractElectrical impedance measurements were performed on 13 atherosclerotic human aortic segments at 67 measuring spots in order to determine whether or not on the basis of these data a distinction can be made between atherosclerotic lesions and normal tissue. Stenosis localization and

Radioiodinate labeling of atherosclerotic plaque imaging agent SP-4 and preliminary experiments

International Nuclear Information System (INIS)

Zhang, Y.; Wu, Z.

2000-01-01

SP-4 was oligopeptide contained 18 amino-acid. It was a part of apolipoprotein B. To study labeling SP-4 with 131 I and its clinical prospect as an atherosclerotic plaque imaging agent. SP-4 was synthesized by solid phase method and identified by amino acid analysis after purification with preparation-model HPLC. SP-4 was labeled with 131 I by the Chloramine-T method and purified through Sephadex G-25, then the radiochemical purity of 131 SP-4 and its stability in vitro were analyzed. 12 New Zealand rabbits were divided into atherosclerosis group (n=7, group A) and control group (n=5, group B). All of them were administrated with bovine serum albumen through i.v., then the rabbits of group A were fed on high cholesterol and high fat diet and group B, on normal diet. Purified 131 I-SP-4 was injected intravenously. %ID/g in blood and thoracic aorta and abdominal aorta at 4 hrs after injection and biodistribution of 131 I-SP-4 was investigated. The amino acid formation of the pure product was identified to be correct through amino-acid analysis. The radiochemical purity of 131 I-SP-4 was 96.2% after being purified, but less than 90% after being stored for 20 hrs. One of 7 rabbits in group A died after being fed for three weeks, the others were alive and atherosclerotic lesions were found after being fed for two mon. On the contrary, 5 rabbits in group B were visualized not to have atherosclerotic lesions. The uptakes of group A and group B at 4 hr after injection were 0.0378±0.0028 and 0.0371±0.038 in blood (p>0.05), 0.0882 ±0.0101 and 0.0276 ±0.0044 in abdominal aorta (p 131 I-SP-4 was mainly excreted through kidneys. SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions. It was potentially useful as an atherosclerotic plaque imaging agent

Macrophage antioxidant protection within atherosclerotic plaques.

Science.gov (United States)

Gieseg, Steven P; Leake, David S; Flavall, Elizabeth M; Amit, Zunika; Reid, Linzi; Yang, Ya-Ting

2009-01-01

Macrophage cells within inflammatory lesions are exposed to a wide range of degrading and cytotoxic molecules including reactive oxygen species. Unlike neutrophils, macrophages do not normally die in this environment but continue to generate oxidants, phagocytose cellular remains, and release a range of cyto-active agents which modulate the immune response. It is this potential of the macrophage cell to survive in an oxidative environment that allows the growth and complexity of advanced atherosclerotic plaques. This review will examine the oxidants encountered by macrophages within an atherosclerotic plaque and describe some of the potential antioxidant mechanisms which enable macrophages to function within inflammatory lesions. Ascorbate, a-tocopherol, and glutathione appear to be central to the protection of macrophages yet additional antioxidant mechanisms appear to be involved. Gamma-Interferon causes macrophages to generate 7,8-dihydroneopterin, neopterin and 3-hydroxyanthranilic acid both of which have antioxidant properties. Manganese superoxide dismutase is also upregulated in macrophages. The evidence that these antioxidants provide further protection, so allowing the macrophage cells to survive within sites of chronic inflammation such as atherosclerotic plaques, will be described.

Nuclear microscopy of atherosclerotic tissue: A review

International Nuclear Information System (INIS)

Watt, Frank; Ren, M.Q.; Xie, J.P.; Tan, B.K.H.; Halliwell, B.

2001-01-01

This paper reviews the work carried out in the Research Centre for Nuclear Microscopy, NUS on the role of iron in coronary heart disease, using the technique of nuclear microscopy to determine the levels of iron and other trace elements in the artery wall and lesions. These investigations have indicated that iron may play a significant role in the development of atherosclerosis, probably through the promotion of cytotoxic free radicals leading to the oxidation of low-density lipoprotein (LDL). Using a rabbit model we have observed that early atherosclerotic lesions, induced by feeding the animals on a 1% cholesterol diet, contain increased levels of iron (up to 8 times) compared with the adjacent healthy artery wall. In a follow-up time sequence study, we have shown that iron accumulation occurs at the onset of lesion formation, which takes place around 4-6 weeks after exposure to the 1% cholesterol diet. As the lesions mature, they enlarge to occupy a significant fraction of the artery wall, and at about 16 weeks the lesions begin to show signs of calcification. In an additional experiment, where the cholesterol fed rabbits were kept anaemic through weekly bleeding, the iron content of the artery wall was reduced and the onset of atherogenesis was delayed. In a further investigation, rabbits were fed on a 1% cholesterol diet and after 6 weeks (corresponding to the period of early lesion formation) a test group was subjected to treatment using the iron chelator desferal. Preliminary results indicate that during the treatment with desferal, lesion development was slowed down

Spatial distribution of osteoblast-specific transcription factor Cbfa1 and bone formation in atherosclerotic arteries.

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Bobryshev, Yuri V; Killingsworth, Murray C; Lord, Reginald S A

2008-08-01

The mechanisms of ectopic bone formation in arteries are poorly understood. Osteoblasts might originate either from stem cells that penetrate atherosclerotic plaques from the blood stream or from pluripotent mesenchymal cells that have remained in the arterial wall from embryonic stages of the development. We have examined the frequency of the expression and spatial distribution of osteoblast-specific factor-2/core binding factor-1 (Osf2/Cbfa1) in carotid and coronary arteries. Cbfa1-expressing cells were rarely observed but were found in all tissue specimens in the deep portions of atherosclerotic plaques under the necrotic cores. The deep portions of atherosclerotic plaques under the necrotic cores were characterized by the lack of capillaries of neovascularization. In contrast, plaque shoulders, which were enriched by plexuses of neovascularization, lacked Cbfa1-expressing cells. No bone formation was found in any of the 21 carotid plaques examined and ectopic bone was observed in only two of 12 coronary plaques. We speculate that the sparse invasion of sprouts of neovascularization into areas underlying the necrotic cores, where Cbfa1-expressing cells reside, might explain the rarity of events of ectopic bone formation in the arterial wall. This study has also revealed that Cbfa1-expressing cells contain alpha-smooth muscle actin and myofilaments, indicating their relationship with arterial smooth muscle cells.

Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease.

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Juan A Rodriguez-Feo

Full Text Available Caveolin-1 (Cav-1 is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice. This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

Science.gov (United States)

Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation

International Nuclear Information System (INIS)

Chen, Jing-Hsien; Tsai, Chia-Wen; Wang, Chi-Ping; Lin, Hui-Hsuan

2013-01-01

Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of > 50 μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu 2+ -induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foam cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent. - Highlights: • The anti-atherosclerotic effect of gossypetin in vitro was examined. • Gossypetin inhibited LDL oxidation. • Gossypetin showed potential in reducing on the formation of foam cells. • Gossypetin functions against ox-LDL through PPARa activation and PPARγ depression

Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation

Energy Technology Data Exchange (ETDEWEB)

Chen, Jing-Hsien [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Chi-Ping [Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Hui-Hsuan, E-mail: linhh@csmu.edu.tw [Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China)

2013-10-15

Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of > 50 μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu{sup 2+}-induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foam cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent. - Highlights: • The anti-atherosclerotic effect of gossypetin in vitro was examined. • Gossypetin inhibited LDL oxidation. • Gossypetin showed potential in reducing on the formation of foam cells. • Gossypetin functions against ox-LDL through PPARa activation and PPARγ depression.

Human macrophage scavenger receptors: Primary structure, expression, and localization in atherosclerotic lesions

International Nuclear Information System (INIS)

Matsumoto, Akiyo; Itakura, Hiroshige; Kodama, Tatsuhiko; Naito, Makoto; Takahashi, Kiyoshi; Ikemoto, Shinji; Asaoka, Hitoshi; Hayakawa, Ikuho; Kanamori, Hiroshi; Takaku, Fumimaro; Aburatani, Hiroyuki; Suzuki, Hiroshi; Kobari, Yukage; Miyai, Tatsuya; Cohen, E.H.; Wydro, R.; Housman, D.E.

1990-01-01

Two types of cDNAs for human macrophage scavenger receptors were cloned from a cDNA library derived from the phorbol ester-treated human monocytic cell line THP-1. The type I and type II human scavenger receptors encoded by these cDNAs are homologous (73% and 71% amino acid identity) to their previously characterized bovine counterparts and consist of six domains: cytoplasmic (I), membrane-spanning (II), spacer (III), α-helical coiled-coil (IV), collagen-like (V), and a type-specific C-terminal (VI). The receptor gene is located on human chromosome 8. The human receptors expressed in CHO-K1 cells mediated endocytosis of modified low density lipoproteins. Two mRNAs, 4.0 and 3.2 kilobases, have been detected in human liver, placenta, and brain. Immunohistochemical studies using an anti-peptide antibody which recognizes human scavenger receptors indicated the presence of the scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of scavenger receptors in atherogenesis

QUALITY OF LIFE IN PATIENTS WITH HYPERTENSION, CORONARY HEART DISEASE, AND ATHEROSCLEROTIC LESION OF LOWER EXTREMITY ARTERIES IN THE SECONDARY PREVENTION OF COMPLICATIONS

Directory of Open Access Journals (Sweden)

A. A. Karlov

2014-07-01

Full Text Available Atherosclerotic lesion of lower extremity arteries frequently complicates the long-term course of hypertension and it is generally associated with coronary heart disease. Our study has attempted to evaluate the impact of combination antihypertensive therapy involving amlodipine, bisoprolol, and lisinopril on quality of life in this category of patients.

In vivo magnetic resonance imaging of atherosclerotic lesions with a newly developed Evans blue-DTPA-gadolinium contrast medium in apolipoprotein-E-deficient mice.

Science.gov (United States)

Yasuda, Satoshi; Ikuta, Kenjiro; Uwatoku, Toyokazu; Oi, Keiji; Abe, Kohtaro; Hyodo, Fuminori; Yoshimitsu, Kengo; Sugimura, Kohtaro; Utsumi, Hideo; Katayama, Yoshiki; Shimokawa, Hiroaki

2008-01-01

Magnetic resonance imaging (MRI) contrast agents that specifically detect atherosclerotic plaque may be useful for the noninvasive detection of the plaque. We have recently developed a new contrast agent, Evans blue-DTPA-gadolinium (EB-DTPA-Gd), which selectively accumulates vascular lesions with endothelial removal. In this study, we examined whether EB-DTPA-Gd is also useful for in vivo imaging of atherosclerotic plaques. We used male apolipoprotein-E-deficient (ApoE-/-) mice of different ages (3, 6 and 12 months old) and age-matched male wild-type mice. After a single intravenous administration of EB-DTPA-Gd (160 microM/kg body weight), MRI T(1) signal was obtained in vivo. Increased signal intensity in the aortic wall was noted within 10-20 min after intravenous injection of EB-DTPA-Gd and was maintained for 30 min. The MRI enhancement in the aorta of ApoE-/- mice was increased in accordance with age, whereas no such enhancement was noted in wild-type mice. Histological examination demonstrated that there was a topological correlation between the site of MRI enhancement and that of atherosclerotic plaque. These results indicate that EB-DTPA-Gd is a useful MRI contrast medium for the in vivo detection of atherosclerotic plaques. Copyright (c) 2007 S. Karger AG, Basel.

Thrombectomy in Acute Stroke With Tandem Occlusions From Dissection Versus Atherosclerotic Cause

DEFF Research Database (Denmark)

Gory, Benjamin; Piotin, Michel; Haussen, Diogo C

2017-01-01

BACKGROUND AND PURPOSE: Tandem steno-occlusive lesions were poorly represented in randomized trials and represent a major challenge for endovascular thrombectomy in acute anterior circulation strokes. The impact of the cervical carotid lesion cause (ie, atherosclerotic versus dissection) on outcome......-2). Secondary efficacy outcomes included successful reperfusion (modified Thrombolysis in Cerebrovascular Infarction scores of 2b-3), time to reperfusion, and safety outcomes encompassed procedural complications, symptomatic intracerebral hemorrhage, and 90-day mortality. RESULTS: Among the 295 included...... patients, 65 had cervical carotid dissection and 230 had cervical carotid atherosclerotic cause. The rate of favorable outcome was 56.3% in the dissection group versus 47.6% in the atherosclerotic arm (center-, age-, and admission National Institutes of Health Stroke Scale-adjusted odds ratio, 1.08; 95...

Evaluation of biodistribution and imaging of atherosclerotic lesions using 111In-labeled low-density lipoprotein

International Nuclear Information System (INIS)

Yamashina, Hisayo

1993-01-01

111 In-labeled low-density lipoprotein (LDL) was administered to Watanabe heritable hyperlipidemic rabbits (WHHL group) and control rabbits (control group) to evaluate its biodistribution and scintigraphic images by γ-camera and radioactivity of each organ. With external imaging, the heart, liver, kidney, bone and spleen of each rabbit were observed. By setting the region of interest, the liver/heart ratio of the WHHL group was significantly lower than that of the control group (p 111 In-labeled-LDL was recognized in the aortic arch, bifurcation of intercostal and celiac artery in the WHHL group. By the use of labeled LDL with the combination of γ-camera, it is capable of detecting the regulation of lipoprotein metabolism and imaging atherosclerotic lesions externally. (author)

Inhibiting extracellular matrix metalloproteinase inducer maybe beneficial for diminishing the atherosclerotic plaque instability

Directory of Open Access Journals (Sweden)

Xie S

2009-01-01

Full Text Available Atherosclerotic plaque rupture and local thrombosis activation in the artery cause acute serious incidents such as acute coronary syndrome and stroke. The exact mechanism of plaque rupture remains unclear but excessive degradation of the extracellular matrix scaffold by matrix-degrading metalloproteinases (MMPs has been implicated as one of the major molecular mechanisms in this process. Convincing evidence is available to prove that extracellular matrix metalloproteinase inducer (EMMPRIN induces MMP expression and is involved in the inflammatory responses in the artery wall. The inflammation and MMPs have been shown to play a critical role for atherosclerotic lesion development and progression. More recent data showed that increased EMMPRIN expression was associated with vulnerable atherosclerotic lesions. Therefore, we speculate that EMMPRIN may be pivotal for atherosclerotic plaque instability, and hence inhibition of EMMPRIN expression could be a promising approach for the prevention or treatment of atheroma instability.

Folic Acid Supplementation Delays Atherosclerotic Lesion Development by Modulating MCP1 and VEGF DNA Methylation Levels In Vivo and In Vitro

Science.gov (United States)

Cui, Shanshan; Li, Wen; Lv, Xin; Wang, Pengyan; Gao, Yuxia; Huang, Guowei

2017-01-01

The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells. We analyzed atherosclerotic lesion histology, folate concentration, homocysteine concentration, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and DNA methyltransferase activity, as well as monocyte chemotactic protein-1 (MCP1) and vascular endothelial growth factor (VEGF) expression and promoter methylation. Folic acid reduced atherosclerotic lesion size in ApoE knockout mice. The underlying folic acid protective mechanism appears to operate through regulating the normal homocysteine state, upregulating the SAM: SAH ratio, elevating DNA methyltransferase activity and expression, altering MCP1 and VEGF promoter methylation, and inhibiting MCP1 and VEGF expression. We conclude that folic acid supplementation effectively prevented atherosclerosis by modifying DNA methylation through the methionine cycle, improving DNA methyltransferase activity and expression, and thus changing the expression of atherosclerosis-related genes. PMID:28475147

Imaging of lipids in atherosclerotic lesion in aorta from ApoE/LDLR-/- mice by FT-IR spectroscopy and Hierarchical Cluster Analysis.

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P Wrobel, Tomasz; Mateuszuk, Lukasz; Chlopicki, Stefan; Malek, Kamilla; Baranska, Malgorzata

2011-12-21

Spectroscopy-based approaches can provide an insight into the biochemical composition of a tissue sample. In the present work Fourier transform infrared (FT-IR) spectroscopy was used to develop a reliable methodology to study the content of free fatty acids, triglycerides, cholesteryl esters as well as cholesterol in aorta from mice with atherosclerosis (ApoE/LDLR(-/-) mice). In particular, distribution and concentration of palmitic, oleic and linoleic acid derivatives were analyzed. Spectral analysis of pure compounds allowed for clear discrimination between free fatty acids and other similar moieties based on the carbonyl band position (1699-1710 cm(-1) range). In order to distinguish cholesteryl esters from triglycerides a ratio of carbonyl band to signal at 1010 cm(-1) was used. Imaging of lipids in atherosclerotic aortic lesions in ApoE/LDLR(-/-) mice was followed by Hierarchical Cluster Analysis (HCA). The aorta from C57Bl/6J control mice (fed with chow diet) was used for comparison. The measurements were completed with an FT-IR spectrometer equipped with a 128 × 128 FPA detector. In cross-section of aorta from ApoE/LDLR(-/-) mice a region of atherosclerotic plaque was clearly identified by HCA, which was later divided into 2 sub-regions, one characterized by the higher content of cholesterol, while the other by higher contents of cholesteryl esters. HCA of tissues deposited on normal microscopic glass, hence limited to the 2200-3800 cm(-1) spectral range, also identified a region of atherosclerotic plaque. Importantly, this region correlates with the area stained by standard histological staining for atherosclerotic plaque (Oil Red O). In conclusion, the use of FT-IR and HCA may provide a novel tool for qualitative and quantitative analysis of contents and distribution of lipids in atherosclerotic plaque.

Kinetic modeling of low density lipoprotein oxidation in arterial wall and its application in atherosclerotic lesions prediction.

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Karimi, Safoora; Dadvar, Mitra; Modarress, Hamid; Dabir, Bahram

2013-01-01

Oxidation of low-density lipoprotein (LDL) is one of the major factors in atherogenic process. Trapped oxidized LDL (Ox-LDL) in the subendothelial matrix is taken up by macrophage and leads to foam cell generation creating the first step in atherosclerosis development. Many researchers have studied LDL oxidation using in vitro cell-induced LDL oxidation model. The present study provides a kinetic model for LDL oxidation in intima layer that can be used in modeling of atherosclerotic lesions development. This is accomplished by considering lipid peroxidation kinetic in LDL through a system of elementary reactions. In comparison, characteristics of our proposed kinetic model are consistent with the results of previous experimental models from other researches. Furthermore, our proposed LDL oxidation model is added to the mass transfer equation in order to predict the LDL concentration distribution in intima layer which is usually difficult to measure experimentally. According to the results, LDL oxidation kinetic constant is an important parameter that affects LDL concentration in intima layer so that existence of antioxidants that is responsible for the reduction of initiating rates and prevention of radical formations, have increased the concentration of LDL in intima by reducing the LDL oxidation rate. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Estudo histopatológico de lesões ateroscleróticas em suínos de raça Alentejana Histopathological study of atherosclerotic lesions in Alentejano pigs

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A. Ramos

2007-01-01

Full Text Available Neste trabalho experimental procedeu-se à medição da espessura e à caracterização histológica de lesões ateroscleróticas, em suínos de raça Alentejana, procurando-se estabelecer uma relação entre estas e os valores dos parâmetros sanguíneos associados ao desenvolvimento deste processo patológico. As concentrações plasmáticas de triacilgliceróis, fosfolípidos, colesterol total, colesterol livre, LDLc e HDLc foram determinadas por métodos enzimáticos. Foram também feitas análises histopatológicas a amostras da artéria coronária esquerda. Os animais foram divididos em 2 grupos de 6 indivíduos cada: Grupo I, com elevada colesterolémia (4,25 mmol/L e Grupo II, com níveis normais (2,53 mmol/L. Os valores do ganho médio diário (GMD dos dois grupos foram semelhantes. Os animais do Grupo I apresentaram valores significativamente mais elevados (P=0,001 para: colesterol total, colesterol livre, colesterol esterificado e LDLc. A área de lesão foi significativamente superior (P=0,05 no Grupo I. Verificou-se uma relação linear entre a área de lesão (fases iniciais do tipo I e II e os teores plasmáticos de colesterol total, de LDLc e de colesterol livre, o que sugere a influência destes parâmetros na dimensão da área de lesão. Os resultados deste trabalho sugerem que os suínos de raça Alentejana podem desenvolver lesões ateroscleróticas ao longo do seu ciclo de vida, tal como o observado em humanos e outras raças de suínos. Estas lesões estão associadas a hipercolesterolemia que poderão ser devidas a mutações genéticas em apolipoproteínas, sistemas enzimáticos ou receptores. São necessários estudos futuros, quer a nível histológico quer a nível de biologia molecular, para um maior aprofundamento do conhecimento das lesões ateroscleróticas em suínos de raça Alentejana.The present study aimed to assess the histopathological characterization of atherosclerotic lesions in Alentejano pigs, and to

Macrophage Liver Kinase B1 Inhibits Foam Cell Formation and Atherosclerosis.

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Liu, Zhaoyu; Zhu, Huaiping; Dai, Xiaoyan; Wang, Cheng; Ding, Ye; Song, Ping; Zou, Ming-Hui

2017-10-13

LKB1 (liver kinase B1) is a serine/threonine kinase and tumor suppressor, which regulates the homeostasis of hematopoietic cells and immune responses. Macrophages transform into foam cells upon taking-in lipids. No role for LKB1 in foam cell formation has previously been reported. We sought to establish the role of LKB1 in atherosclerotic foam cell formation. LKB1 expression was examined in human carotid atherosclerotic plaques and in western diet-fed atherosclerosis-prone Ldlr -/- and ApoE -/- mice. LKB1 expression was markedly reduced in human plaques when compared with nonatherosclerotic vessels. Consistently, time-dependent reduction of LKB1 levels occurred in atherosclerotic lesions in western diet-fed Ldlr -/- and ApoE -/- mice. Exposure of macrophages to oxidized low-density lipoprotein downregulated LKB1 in vitro. Furthermore, LKB1 deficiency in macrophages significantly increased the expression of SRA (scavenger receptor A), modified low-density lipoprotein uptake and foam cell formation, all of which were abolished by blocking SRA. Further, we found LKB1 phosphorylates SRA resulting in its lysosome degradation. To further investigate the role of macrophage LKB1 in vivo, ApoE -/- LKB1 fl/fl LysM cre and ApoE -/- LKB1 fl/fl mice were fed with western diet for 16 weeks. Compared with ApoE -/- LKB1 fl/fl wild-type control, ApoE -/- LKB1 fl/fl LysM cre mice developed more atherosclerotic lesions in whole aorta and aortic root area, with markedly increased SRA expression in aortic root lesions. We conclude that macrophage LKB1 reduction caused by oxidized low-density lipoprotein promotes foam cell formation and the progression of atherosclerosis. © 2017 American Heart Association, Inc.

Impact of the B Cell Growth Factor APRIL on the Qualitative and Immunological Characteristics of Atherosclerotic Plaques.

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Bernelot Moens, Sophie J; van Leuven, Sander I; Zheng, Kang H; Havik, Stefan R; Versloot, Miranda V; van Duivenvoorde, Leonie M; Hahne, Michael; Stroes, Erik S G; Baeten, Dominique L; Hamers, Anouk A J

2016-01-01

Studies on the role of B lymphocytes in atherosclerosis development, have yielded contradictory results. Whereas B lymphocyte-deficiency aggravates atherosclerosis in mice; depletion of mature B lymphocytes reduces atherosclerosis. These observations led to the notion that distinct B lymphocyte subsets have different roles. B1a lymphocytes exert an atheroprotective effect, which has been attributed to secretion of IgM, which can be deposited in atherosclerotic lesions thereby reducing necrotic core formation. Tumor necrosis factor (TNF)-family member 'A Proliferation-Inducing Ligand' (APRIL, also known as TNFSF13) was previously shown to increase serum IgM levels in a murine model. In this study, we investigated the effect of APRIL overexpression on advanced lesion formation and composition, IgM production and B cell phenotype. We crossed APRIL transgenic (APRIL-Tg) mice with ApoE knockout (ApoE-/-) mice. After a 12-week Western Type Diet, ApoE-/-APRIL-Tg mice and ApoE-/- littermates showed similar increases in body weight and lipid levels. Histologic evaluation showed no differences in lesion size, stage or necrotic area. However, smooth muscle cell (α-actin stain) content was increased in ApoE-/-APRIL-Tg mice, implying more stable lesions. In addition, increases in both plaque IgM deposition and plasma IgM levels were found in ApoE-/-APRIL-Tg mice compared with ApoE-/- mice. Flow cytometry revealed a concomitant increase in peritoneal B1a lymphocytes in ApoE-/-APRIL-Tg mice. This study shows that ApoE-/-APRIL-Tg mice have increased oxLDL-specific serum IgM levels, potentially mediated via an increase in B1a lymphocytes. Although no differences in lesion size were found, transgenic ApoE-/-APRIL-Tg mice do show potential plaque stabilizing features in advanced atherosclerotic lesions.

Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits

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Shoucui Gao

2017-01-01

Full Text Available High levels of plasma high-density lipoprotein-cholesterol (HDL-C are inversely associated with the risk of atherosclerosis and other cardiovascular diseases; thus, pharmacological inhibition of cholesteryl ester transfer protein (CETP is considered to be a therapeutic method of raising HDL-C levels. However, many CETP inhibitors have failed to achieve a clinical benefit despite raising HDL-C. In the study, we generated transgenic (Tg rabbits that overexpressed the human CETP gene to examine the influence of CETP on the development of atherosclerosis. Both Tg rabbits and their non-Tg littermates were fed a high cholesterol diet for 16 weeks. Plasma lipids and body weight were measured every 4 weeks. Gross lesion areas of the aortic atherosclerosis along with lesional cellular components were quantitatively analyzed. Overexpression of human CETP did not significantly alter the gross atherosclerotic lesion area, but the number of macrophages in lesions was significantly increased. Overexpression of human CETP did not change the plasma levels of total cholesterol or low-density lipoprotein cholesterol but lowered plasma HDL-C and increased triglycerides. These data revealed that human CETP may play an important role in the development of atherosclerosis mainly by decreasing HDL-C levels and increasing the accumulation of macrophage-derived foam cells.

MRI of the transplanted endothelial progenitor cells for prevent atherosclerotic plaque formation

International Nuclear Information System (INIS)

Ma Zhanlong; Teng Gaojun; Mai Xiaoli; Chen Jun; Sun Junhui; Zhang Hongying; Yu Hui; Li Guozhao

2007-01-01

Objective: To evaluate the 1.5 T magnetic resonance imaging system to depict and track in vivo of magnetically labeled endothelial progenitor cells (EPCs), and to study the possibility for preventing the atherosclerotic plaque formation in New Zealand rabbit model of carotid arterial injury after transplantation. Methods: New Zealand rabbit EPCs were isolated, confirmed, expanded and then incubated with home synthesized Fe 2 O 3 -PLL, Prussian blue stain was performed for showing intracellular irons. The model of carotid arterial injury was performed by 2.5F balloons, the group A of 8 rabbits received magnetically labeled EPCs, group B of 3 rabbits received fluorescent-labeled EPCs and the group C of 5 rabbits were given same volume saline injection after endothelial injury of the carotid artery. MR imaging and histology were performed and compared 4 days later for randomly chosen three rabbit, each from one of the three group; all the other rabbits were fed with high lipid diet and examed using MR imaging and histology after 15 weeks. Results: Epcs labeling efficiency was more than 95% by Prussian blue stain, 4 days after transplantation of EPCs, only in group A, the injured endothelium of carotid artery had signal intensity loss in T 2 * WI, which were correlated well with the area where the most Prussian blue staining positive cells were found in histopathology analyses. The rabbits of group A and B which received EPCs transplantation exhibited fewer plaques formation than those of the group C (P 2 O 3 -PLL. The 1.5 T magnetic resonance imaging system could depict and monitor the magnetically labeled endothelial progenitor cells homing to the injured endothelium of the artery, and EPCs contribute to preventing atherosclerotic plaque formation in New Zealand rabbit model of atherosclerosis. (authors)

CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration.

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Xu, Suining; Li, Lihua; Yan, Jinchuan; Ye, Fei; Shao, Chen; Sun, Zhen; Bao, Zhengyang; Dai, Zhiyin; Zhu, Jie; Jing, Lele; Wang, Zhongqun

2018-01-01

Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration. In vivo study and in vitro study were performed. For the in vivo investigation, CML/CD36 accelerated atherosclerotic progression via promoting the accumulation of macrophage-derived foam cells in aorta and inhibited macrophage-derived foam cells in aorta migrating to the para-aorta lymph node of diabetic apoE -/- mice. For the in vitro investigation, CML/CD36 inhibited RAW264.7-derived foam cell migration through NOX-derived ROS, FAK phosphorylation, Arp2/3 complex activation and F-actin polymerization. Thus, we concluded that CML/CD36 inhibited foam cells of plaque migrating to para-aorta lymph nodes, accelerating atherosclerotic progression. The corresponding mechanism may be via free cholesterol, ROS generation, p-FAK, Arp2/3, F-actin polymerization. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Intra-plaque production of platelet-activating factor correlates with neoangiogenesis in human carotid atherosclerotic lesions.

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Lupia, Enrico; Pucci, Angela; Peasso, Paolo; Merlo, Maurizio; Baron, Paolo; Zanini, Cristina; Del Sorbo, Lorenzo; Rizea-Savu, Simona; Silvestro, Luigi; Forni, Marco; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

2003-09-01

Platelet-activating factor (PAF) is a phospholipid mediator synthesized by activated inflammatory and endothelial cells. Recently PAF has been shown to contribute to neoangiogenesis in several experimental models. Here we evaluated the presence of PAF and its potential role in neovascularization within human atherosclerotic plaques. The amount of PAF extracted from 18 carotid plaques (266.65+/-40.07 pg/100 mg dry tissue; mean +/- SE) was significantly higher than that extracted from 18 normal arterial specimens (6 from carotid artery and 12 from aorta) (4.72+/-2.31 pg/100 mg dry tissue; mean +/- SE). The levels of PAF significantly correlated with the infiltration of CD68-positive monocytes and the extent of neovascularization, detected as von Willebrand Factor-positive cells. The amount of PAF also correlated with the area occupied by TNF-alpha-expressing cells. The absence of enhanced level of PAF in the circulation of atherosclerotic patients suggests a local production of this mediator within the plaque. The lipid extracts of atherosclerotic plaques containing high levels of PAF-bioactivity, but not those of control arteries, were angiogenic in a murine Matrigel model. WEB 2170, a specific PAF receptor antagonist, significantly prevented angiogenesis induced by the lipid extracts of atherosclerotic plaques. Our results indicate a local production of PAF within the atherosclerotic plaques and suggest that it may contribute to intra-plaque neoangiogenesis.

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

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Son, Dong Ju [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Kim, Soo Yeon [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Han, Seong Su [University of Iowa Carver College of Medicine, Department of Pathology, Iowa City, IA (United States); Kim, Chan Woo [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Kumar, Sandeep [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Park, Byeoung Soo [Nanotoxtech Co., Ansan (Korea, Republic of); Lee, Sung Eun [Division of Applied Biology and Chemistry, Kyungpook National University, Daegu (Korea, Republic of); Yun, Yeo Pyo [College of Pharmacy, Chungbuk National University, Cheongju (Korea, Republic of); Jo, Hanjoong, E-mail: hjo@emory.edu [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Park, Young Hyun, E-mail: pyh012@sch.ac.kr [Department of Food Science and Nutrition, College of Natural Sciences, Soonchunhyang University, Asan (Korea, Republic of)

2012-10-19

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

Add-On Effect of Probucol in Atherosclerotic, Cholesterol-Fed Rabbits Treated with Atorvastatin

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Keyamura, Yuka; Nagano, Chifumi; Kohashi, Masayuki; Niimi, Manabu; Nozako, Masanori; Koyama, Takashi; Yasufuku, Reiko; Imaizumi, Ayako; Itabe, Hiroyuki; Yoshikawa, Tomohiro

2014-01-01

Objective Lowering the blood concentration of low-density lipoprotein (LDL) cholesterol is the primary strategy employed in treating atherosclerotic disorders; however, most commonly prescribed statins prevent cardiovascular events in just 30% to 40% of treated patients. Therefore, additional treatment is required for patients in whom statins have been ineffective. In this study of atherosclerosis in rabbits, we examined the effect of probucol, a lipid-lowering drug with potent antioxidative effects, added to treatment with atorvastatin. Methods and Results Atherosclerosis was induced by feeding rabbits chow containing 0.5% cholesterol for 8 weeks. Probucol 0.1%, atorvastatin 0.001%, and atorvastatin 0.003% were administered solely or in combination for 6 weeks, beginning 2 weeks after the start of atherosclerosis induction. Atorvastatin decreased the plasma concentration of non-high-density lipoprotein cholesterol (non-HDLC) dose-dependently; atorvastatin 0.003% decreased the plasma concentration of non-HDLC by 25% and the area of atherosclerotic lesions by 21%. Probucol decreased the plasma concentration of non-HDLC to the same extent as atorvastatin (i.e., by 22%) and the area of atherosclerotic lesions by 41%. Probucol with 0.003% atorvastatin decreased the plasma concentration of non-HDLC by 38% and the area of atherosclerotic lesions by 61%. Co-administration of probucol with atorvastatin did not affect the antioxidative effects of probucol, which were not evident on treatment with atorvastatin alone, such as prevention of in vitro LDL-oxidation, increase in paraoxonase-1 activity of HDL, and decreases in plasma and plaque levels of oxidized-LDL in vivo. Conclusions Probucol has significant add-on anti-atherosclerotic effects when combined with atorvastatin treatment; suggesting that this combination might be beneficial for treatment of atherosclerosis. PMID:24810608

Impact of glutathione peroxidase-1 deficiency on macrophage foam cell formation and proliferation: implications for atherogenesis.

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Fei Cheng

Full Text Available Clinical and experimental evidence suggests a protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx-1 in the atherogenic process. GPx-1 deficiency accelerates atherosclerosis and increases lesion cellularity in ApoE(-/- mice. However, the distribution of GPx-1 within the atherosclerotic lesion as well as the mechanisms leading to increased macrophage numbers in lesions is still unknown. Accordingly, the aims of the present study were (1 to analyze which cells express GPx-1 within atherosclerotic lesions and (2 to determine whether a lack of GPx-1 affects macrophage foam cell formation and cellular proliferation. Both in situ-hybridization and immunohistochemistry of lesions of the aortic sinus of ApoE(-/- mice after 12 weeks on a Western type diet revealed that both macrophages and - even though to a less extent - smooth muscle cells contribute to GPx-1 expression within atherosclerotic lesions. In isolated mouse peritoneal macrophages differentiated for 3 days with macrophage-colony-stimulating factor (MCSF, GPx-1 deficiency increased oxidized low density-lipoprotein (oxLDL induced foam cell formation and led to increased proliferative activity of peritoneal macrophages. The MCSF- and oxLDL-induced proliferation of peritoneal macrophages from GPx-1(-/-ApoE(-/- mice was mediated by the p44/42 MAPK (p44/42 mitogen-activated protein kinase, namely ERK1/2 (extracellular-signal regulated kinase 1/2, signaling pathway as demonstrated by ERK1/2 signaling pathways inhibitors, Western blots on cell lysates with primary antibodies against total and phosphorylated ERK1/2, MEK1/2 (mitogen-activated protein kinase kinase 1/2, p90RSK (p90 ribosomal s6 kinase, p38 MAPK and SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase, and immunohistochemistry of mice atherosclerotic lesions with antibodies against phosphorylated ERK1/2, MEK1/2 and p90RSK. Representative effects of GPx-1 deficiency on both macrophage proliferation and

Adaptive lesion formation using dual mode ultrasound array system

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Liu, Dalong; Casper, Andrew; Haritonova, Alyona; Ebbini, Emad S.

2017-03-01

We present the results from an ultrasound-guided focused ultrasound platform designed to perform real-time monitoring and control of lesion formation. Real-time signal processing of echogenicity changes during lesion formation allows for identification of signature events indicative of tissue damage. The detection of these events triggers the cessation or the reduction of the exposure (intensity and/or time) to prevent overexposure. A dual mode ultrasound array (DMUA) is used for forming single- and multiple-focus patterns in a variety of tissues. The DMUA approach allows for inherent registration between the therapeutic and imaging coordinate systems providing instantaneous, spatially-accurate feedback on lesion formation dynamics. The beamformed RF data has been shown to have high sensitivity and specificity to tissue changes during lesion formation, including in vivo. In particular, the beamformed echo data from the DMUA is very sensitive to cavitation activity in response to HIFU in a variety of modes, e.g. boiling cavitation. This form of feedback is characterized by sudden increase in echogenicity that could occur within milliseconds of the application of HIFU (see http://youtu.be/No2wh-ceTLs for an example). The real-time beamforming and signal processing allowing the adaptive control of lesion formation is enabled by a high performance GPU platform (response time within 10 msec). We present results from a series of experiments in bovine cardiac tissue demonstrating the robustness and increased speed of volumetric lesion formation for a range of clinically-relevant exposures. Gross histology demonstrate clearly that adaptive lesion formation results in tissue damage consistent with the size of the focal spot and the raster scan in 3 dimensions. In contrast, uncontrolled volumetric lesions exhibit significant pre-focal buildup due to excessive exposure from multiple full-exposure HIFU shots. Stopping or reducing the HIFU exposure upon the detection of such an

IAP survivin regulates atherosclerotic macrophage survival

NARCIS (Netherlands)

Blanc-Brude, Olivier P.; Teissier, Elisabeth; Castier, Yves; Lesèche, Guy; Bijnens, Ann-Pascal; Daemen, Mat; Staels, Bart; Mallat, Ziad; Tedgui, Alain

2007-01-01

Inflammatory macrophage apoptosis is critical to atherosclerotic plaque formation, but its mechanisms remain enigmatic. We hypothesized that inhibitor of apoptosis protein (IAP) survivin regulates macrophage death in atherosclerosis. Western blot analysis revealed discrete survivin expression in

Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

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Kovanen, Petri T; Bot, Ilze

2017-12-05

Mast cells are potent actors involved in inflammatory reactions in various tissues, including both in the intimal and the adventitial layers of atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast cells are activated to degranulate, and thereby triggered to release an abundance of preformed inflammatory mediators, notably histamine, heparin, neutral proteases and cytokines stored in their cytoplasmic secretory granules. Depending on the stimulus, mast cell activation may also launch prolonged synthesis and secretion of single bioactive molecules, such as cytokines and derivatives of arachidonic acid. The mast cell-derived mediators may impede the functions of different types of cells present in atherosclerotic lesions, and also compromise the structural and functional integrity of the intimal extracellular matrix. In the adventitial layer of atherosclerotic coronary arteries, mast cells locate next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may activate mast cells to release vasoactive compounds capable of triggering local vasoconstriction. The concerted actions of arterial mast cells have the potential to contribute to the initiation and progression of atherosclerosis, and ultimately to destabilization and rupture of an advanced atherosclerotic plaque with ensuing atherothrombotic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Radioiodine labelled SP-4 as an imaging agent for atherosclerotic plaques

International Nuclear Information System (INIS)

Zhang Yongxue; Wu Zhijian; Cao Wei

2000-01-01

The clinical prospect of radioiodinated SP-4 as an atherosclerotic plaque imaging agent was studied. The SP-4 was synthesized by a solid phase method and identified by an amino acid analysis after purification with HPLC. SP-4 was labelled with 131 I and 125 I by the Chloramine-T method and purified through Sephadex G-25 column. Twelve New Zealand rabbits were divided into an atherosclerotic group (n = 7, AR) and a control group (n = 5, NR). All of the atherosclerotic rabbits were intravenous administrated with bovine serum albumin, then feb with high cholesterol and fat diet. 125 I-SP-4 was intravenous administrated to the rabbits of both groups. The biodistribution of 125 I-SP-4 in rabbits was investigated. The uptakes (% ID/g) in blood and thoracic aorta and abdominal aorta were calculated 4 hours postinjection. Macro-autoradiography and micro-autoradiography were performed in 2 AR atherosclerotic abdominal aortas. The clearance of radioactivity from plasma was very rapid. 125 I-SP-4 was mainly excreted through kidneys. The radioactive uptakes of abdominal aorta and thoracic aorta of AR at 4 hours postinjection were significantly higher than that of NR. The films of macro-autoradiography showed focal accumulation of the radioactivity in the areas of a newly formed edges of atherosclerotic plaques. On the slices of micro-autoradiography, the obvious radioactive accumulation could be found in the atherosclerotic plaques. Thus it was seen that the SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions, it is potentially useful as an atherosclerotic plaque imaging agent

Cutting-Balloon Angioplasty Versus Balloon Angioplasty as Treatment for Short Atherosclerotic Lesions in the Superficial Femoral Artery: Randomized Controlled Trial

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Poncyljusz, Wojciech, E-mail: wponcyl@poczta.onet.pl; Falkowski, Aleksander, E-mail: bakhis@hot.pl [Pomeranian Medical University, Department of Interventional Radiology (Poland); Safranow, Krzysztof, E-mail: chrissaf@mp.pl; Rac, Monika, E-mail: carmon@pum.edu.pl [Pomeranian Medical University, Department of Biochemistry and Medical Chemistry (Poland); Zawierucha, Dariusz, E-mail: dariusz13@yahoo.com [Interventional Radiology, Sacred Heart Medical Center, River Bend (United States)

2013-12-15

Purpose: To evaluate the treatments of a short-segment atherosclerotic stenosis in the superficial femoral arteries with the cutting balloon angioplasty (CBA) versus conventional balloon angioplasty [percutaneous transluminal angioplasty (PTA)] in a randomized controlled trial. Material and Methods: The study group comprised 60 patients (33 men, 27 women; average age 64 years) with a short ({<=}5 cm) focal SFA de novo atherosclerotic stenosis associated with a history of intermittent claudication or rest pain. The primary end point of this study was the rate of binary restenosis in the treated segment 12 months after the intervention. All patients were evenly randomized to either the PTA or CBA treatment arms. Follow-up angiograms and ankle-brachial index (ABI) measurements were performed after 12 months. The evaluation of the restenosis rates and factors influencing its occurrence were calculated by logistic regression analysis. Results: In the intention-to-treat analysis, restenosis rates after 2-month follow-up were 9 of 30 (30 %) in the PTA group and 4 of 30 (13 %) in the CBA group (p = 0.117). In the actual treatment analysis, after exclusion of patients who required nitinol stent placement for a suboptimal result after angioplasty alone (5 patients in the PTA group and none in the CBA group), restenosis rates were 9 of 25 (36 %) and 4 of 30 (13 %), respectively (p = 0.049). In the intention-to-treat analysis there were also significant differences in ABI values between the PTA and CBA groups at 0.77 {+-} 0.11 versus 0.82 {+-} 0.12, respectively (p = 0.039), at 12 months. Conclusion: Based on the presented results of the trial, CBA seems to be a safer and more effective than PTA for treatment of short atherosclerotic lesions in the superior femoral artery.

Endothelial NLRP3 inflammasome activation and arterial neointima formation associated with acid sphingomyelinase during hypercholesterolemia

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Saisudha Koka

2017-10-01

Full Text Available The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM and ceramide associated membrane raft (MR signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto or cholesterol crystal (ChC markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs, as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene. In CAECs with NLRP3 inflammasome formation, membrane raft (MR clustering with NADPH oxidase subunits was found remarkably increased as shown by CTXB (MR marker and gp91phox aggregation indicating the formation of MR redox signaling platforms. This MR clustering was blocked by MR disruptor (MCD, ROS scavenger (Tempol and TXNIP inhibitor (verapamil, accompanied by attenuation of 7-Keto or ChC-induced increase in caspase-1 activity. In animal experiments, Western diet fed mice with partially ligated left carotid artery (PLCA were found to have significantly increased neointimal formation, which was associated with increased NLRP3 inflammasome formation and IL-1β production in the intima of Asm+/+ mice but not in Asm-/- mice. These results suggest that Asm gene and ceramide associated MR clustering are essential to endothelial inflammasome activation and dysfunction in the carotid arteries, ultimately determining the extent of atherosclerotic lesions.

Collagen and related extracellular matrix proteins in atherosclerotic plaque development.

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Shami, Annelie; Gonçalves, Isabel; Hultgårdh-Nilsson, Anna

2014-10-01

The structure, composition and turnover of the extracellular matrix (ECM) as well as cell-matrix interactions are crucial in the developing atherosclerotic plaque. There is a need for further insight into specific proteins in the ECM and their functions in the developing plaque, and during the last few years a number of publications have highlighted this very important field of research. These novel findings will be addressed in the present review. This review covers literature focused on collagen and ECM proteins interacting with collagen, and what their roles may be in plaque development. Acute myocardial infarction and stroke are common diseases that cause disability and mortality, and the underlying mechanism is often the rupture of a vulnerable atherosclerotic plaque. The vascular ECM and the tissue repair in the atherosclerotic lesion are important players in plaque progression. Understanding how specific proteins in the ECM interact with cells in the plaque and affect the fate of the plaque can lead to new treatments for cardiovascular disease.

MR chemical shift imaging and spectroscopy of atherosclerotic plaque

International Nuclear Information System (INIS)

Vinitski, S.; Consigny, P.M.; Shapiro, M.J.; Janes, N.; Smullens, S.N.; Rifkin, M.D.

1989-01-01

The purpose of this study was to develop a technique for in vivo imaging and characterization of atherosclerotic plaque. The authors used a spin-echo technique with a short echo time (TE) of 11 msec. Lipid/water suppression was achieved by means of hybrid chemical shift imaging. Lesions were induced in three rabbits by a combination of balloon denudation of the abdominal aorta and a high-cholesterol diet. Following in vivo imaging of these rabbit aortas and human carotid arteries (1.5 T), the animals were killed or carotid endarterectomy was performed so that the plaques could be excised. The plaques were then analyzed in vitro both histologically and with high-resolution spectroscopy (8.5 T). Use of the short TE improved lesion visualization. The fat/water suppression showed only a small amount of mobile lipids in plaque. Both MR spectroscopic and histologic analysis corroborated these images. The composition of atherosclerotic plaques in both humans and rabbits was demonstrated to be heterogeneous, with predominantly nonmobile lipids. These results suggest that the combination of short TE MR imaging and fat/water suppression can identify plaque and delineate areas containing mobile lipids

IL-1β level in Sudanese patients with atherosclerotic coronary heart ...

African Journals Online (AJOL)

McRoy

studies investigating inflammatory cytokines in atherosclerotic patients with coronary heart disease (CHD).[2,5-7]. However, systemic level of IL-1β may still be unreliable marker for atherosclerosis. This is because systemic level of IL-1β could not faithfully reflect the local inflammatory process near the atheromatous lesions.

Multicolor fluorescence technique to detect apoptotic cells in advanced coronary atherosclerotic plaques

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C Soldani

2009-06-01

Full Text Available Apoptosis occurring in atherosclerotic lesions has been suggested to be involved in the evolution and the structural stability of the plaques. It is still a matter of debate whether apoptosis mainly involves vascular smooth muscle cells (vSMCs in the fibrous tissue or inflammatory (namely foam cells, thus preferentially affecting the cell-poor lipid core of the atherosclerotic plaques. The aim of the present investigation was to detect the presence of apoptotic cells and to estimate their percentage in a series of atherosclerotic plaques obtained either by autopsy or during surgical atherectomy. Apoptotic cells were identified on paraffinembedded sections on the basis of cell nuclear morphology after DNA staining and/or by cytochemical reactions (TUNEL assay, immunodetection of the proteolytic poly (ADP-ribose polymerase-1 [PARP-1] fragment; biochemical procedures (identifying DNA fragmentation or PARP-1 proteolysis were also used. Indirect immunofluorescence techniques were performed to label specific antigens for either vSMCs or macrophages (i.e., the cells which are most likely prone to apoptosis in atherosclerotic lesions: the proper selection of fluorochrome labeling allowed the simultaneous detection of the cell phenotype and the apoptotic characteristics, by multicolor fluorescence techniques. Apoptotic cells proved to be less than 5% of the whole cell population, in atherosclerotic plaque sections: this is, in fact, a too low cell fraction to be detected by widely used biochemical methods, such as agarose gel electrophoresis of low-molecular-weight DNA or Western-blot analysis of PARP-1 degradation. Most apoptotic cells were of macrophage origin, and clustered in the tunica media, near or within the lipid-rich core; only a few TUNEL-positive cells were labeled for antigens specific for vSMCs. These results confirm that, among the cell populations in atherosclerotic plaques, macrophage foam-cells are preferentially involved in apoptosis

PET/CT for atherosclerotic plaque imaging

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Ben-Haim, S.; Technion Institute of Technology, Haifa; Israel, O.; Rambam Medical Center, Haifa

2006-01-01

Atherosclerosis is one of the leading causes of morbidity and mortality in the world. Rupture of atherosclerotic plaques and thrombi formation are the primary mechanisms of myocardial infarction or cerebrovascular accident. Angiography is considered to represent the gold standard technique for imaging of the arterial lumen. However, in recent years it has been realized that the primary determinant of the atherosclerotic plaque stability is the composition of the plaque and other imaging modalities have been suggested. The purpose of this review is to briefly summarize the knowledge accumulated to present date regarding the potential role of fluo deoxyglucose imaging in the assessment of atherosclerosis and to compare this modality to additional available imaging approaches for the detection of vulnerable plaques

Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

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Saffi, Marco Aurélio Lumertz; Furtado, Mariana Vargas; Polanczyk, Carisi Anne; Montenegro, Márlon Munhoz; Ribeiro, Ingrid Webb Josephson; Kampits, Cassio; Haas, Alex Nogueira; Rösing, Cassiano Kuchenbecker; Rabelo-Silva, Eneida Rejane

2015-01-01

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease. PMID:25632316

Baccaurea angulata fruit juice reduces atherosclerotic lesions in diet-induced Hypercholesterolemic rabbits.

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Ibrahim, Muhammad; Ahmed, Idris Adewale; Mikail, Maryam Abimbola; Ishola, Afeez Adekunle; Draman, Samsul; Isa, Muhammad Lokman Md; Yusof, Afzan Mat

2017-07-07

Atherosclerosis is the most common disease of large and medium-sized arteries linked to oxidative stress, dyslipidemia as well as chronic inflammation. The aim of this study was to evaluate the potential health benefits of Baccaurea angulata (BA) fruit juice on the aorta of diet-induced hypercholesterolemic rabbits, to detect an accumulation of fatty streak and evaluate the percentage of atherosclerotic lesion accrued. Thirty-five healthy male adults New Zealand White rabbits were assigned to seven different groups. Four groups were fed 1% cholesterol diet and 0, 0.5, 1.0, and 1.5 mL of BA fruit juice per kg of rabbit daily (atherogenic groups), while the other three groups were fed commercial rabbit pellet and 0, 0.5, and 1.0 mL of juice per kg of rabbit daily (normocholesterolemic groups) for 90 days. The thoracic and abdominal aorta between the heart origin and bifurcation into iliac arteries of all the rabbits were carefully removed and analyzed accordingly. The supplementation of the high-cholesterol diet of hypercholesterolemic rabbits with only 0.5 mL BA/kg rabbit per day significantly (p < 0.001) improved aortic lipid profile, attenuated aortic fatty streak development and reduced intima thickening. Higher BA doses used (1.0 and 1.5 mL/kg rabbit per day) also significantly (p < 0.001) decreased further the development of aortic fatty streaks, reduced the thickening of the tunica intima layer and preserved endothelial healing following arterial injury. Therefore, BA fruit is a potential novel functional food with effective anti-inflammatory, anti-atherogenic and hypocholesterolemic activities.

SCM-198 attenuates early atherosclerotic lesions in hypercholesterolemic rabbits via modulation of the inflammatory and oxidative stress pathways.

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Zhang, Yanfei; Guo, Wei; Wen, Yadan; Xiong, Qinghui; Liu, Hongrui; Wu, Jian; Zou, Yunzeng; Zhu, Yizhun

2012-09-01

GPx in the aorta. In a rabbit atherosclerotic model, SCM-198 dose-dependently ameliorated the progression of atherosclerotic lesions and vascular dysfunction accompanied by the suppression of inflammatory factors and oxidative stress. These findings suggested that SCM-198 might be a potential agent for the treatment of atherosclerosis. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

Is it possible to estimate cerebro–vascular risk on the basis of the composition of carotid atherosclerotic plaques?

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Pavel Poredoš

2012-02-01

Full Text Available Different models for the prediction of cardiovascular and cerebro-vascular events are used, based on the presence of risk factors. This is a statistical risk-assessment model. Recently, research has been focused on identifying indicators that would enable us to directly assess the risk in certain individuals. These indicators include the detection of the presence and composition of atherosclerotic plaques. Atherosclerotic plaques found in a majority of adults represent a potential cause of vascular complications. Recently, not only thestage of atherosclerotic plaques or the degree of arterial stenosis but also the knowledge of atherosclerotic plaque composition is gaining in importance. Particularly unstable plaques, which are prone to disintegration and the associatedthromboembolic complications, are considered dangerous. Therefore, recently intensive research has been underway to find methods that would enable us to identify the composition and in particular the biological activity of atherosclerotic plaques. Namely, the latter two features determine the stability of plaques or their proneness to rupture and disintegration. While classical angiography is invasive and associated with irradiation, it only provides information on the degree of vascular lumen stenosis but not also on vascular wall composition. Ultrasonography is a basic non-invasive imaging method, which also provides an insight into the composition of vascular wall, however, since mainly superficially situated arteries are accessible by US, its investigation potential in distinguishing between different tissue structures is rather limited. Recent computer programs for analysis of ultrasound images and quantifying various components of atherosclerotic plaques provide a more accurate determination of the composition of atherosclerotic plaques, but do not yield information on the biological activity of atherosclerotic lesions.A newer generation of imaging methods facilitates more

EXTRACRANIAL NON-ATHEROSCLEROTIC PATHOLOGY OF THE CAROTID ARTERY IN THE CAUSES OF ACUTE ISCHEMIC STROKE

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I. P. Dudanov

2017-01-01

Full Text Available Purpose. We present the experience of treatment of patients with cerebral vascular accident by the ischemic type, the cause of which was non-atherosclerotic lesion of brachiocephalic arteries.Materials and methods. During 2011–2015 years 4118 patients with acute ischemic stroke were observed. Of these, 589 patients (14.3% were operated in the acute period of stroke in the period from 4–6 hours to 14 days. The cause of the stroke was various types of pathology of the extracranial divisions of the brachiocephalic arteries (EDBA. Of this number, with atherosclerotic carotid artery stenoses, 336 patients (57.1% were operated on, with non-atherosclerotic pathology of carotid arteries — 253 patients (42.9%. Of these 253 patients, dissection of the intima of the carotid arteries was detected in 10 (3.9% patients, aneurysms in the extracranial segment of the ECA and ICA were detected in 14 (5.5%, and 229 (90.6% revealed various types of tortuosity and kinks carotid arteries and fibrous dysplasia. All patients are operated on. Various types of reconstructions of carotid arteries with a good clinical effect have been performed. There were no lethal outcomes.Concusions. The data obtained in the study confirm the opinion that not only atherosclerotic lesions of the ICA are an indication for surgical treatment at an early date. This stage is an important part of the comprehensive rehabilitation of patients with acute ischemic stroke.

A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

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Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

2014-01-01

Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

Myeloid protein tyrosine phosphatase 1B (PTP1B) deficiency protects against atherosclerotic plaque formation in the ApoE-/- mouse model of atherosclerosis with alterations in IL10/AMPKα pathway.

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Thompson, D; Morrice, N; Grant, L; Le Sommer, S; Ziegler, K; Whitfield, P; Mody, N; Wilson, H M; Delibegović, M

2017-08-01

Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with Type 1 or Type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance due to impaired insulin receptor (IR) signaling. Moreover, inflammatory cells, in particular macrophages, play a key role in pathogenesis of atherosclerosis and insulin resistance in humans. We hypothesized that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR, specifically in macrophages, would have beneficial anti-inflammatory effects and lead to protection against atherosclerosis and CVD. We generated novel macrophage-specific PTP1B knockout mice on atherogenic background (ApoE -/- /LysM-PTP1B). Mice were fed standard or pro-atherogenic diet, and body weight, adiposity (echoMRI), glucose homeostasis, atherosclerotic plaque development, and molecular, biochemical and targeted lipidomic eicosanoid analyses were performed. Myeloid-PTP1B knockout mice on atherogenic background (ApoE -/- /LysM-PTP1B) exhibited a striking improvement in glucose homeostasis, decreased circulating lipids and decreased atherosclerotic plaque lesions, in the absence of body weight/adiposity differences. This was associated with enhanced phosphorylation of aortic Akt, AMPKα and increased secretion of circulating anti-inflammatory cytokine interleukin-10 (IL-10) and prostaglandin E2 (PGE 2 ), without measurable alterations in IR phosphorylation, suggesting a direct beneficial effect of myeloid-PTP1B targeting. Here we demonstrate that inhibiting the activity of PTP1B specifically in myeloid lineage cells protects against atherosclerotic plaque formation, under atherogenic conditions, in an ApoE -/- mouse model of atherosclerosis. Our findings suggest for the first time that macrophage PTP1B targeting could be a therapeutic target for atherosclerosis treatment and reduction of CVD risk.

Monitoring of macrophage accumulation in statin-treated atherosclerotic mouse model using sodium iodide symporter imaging system

International Nuclear Information System (INIS)

Yoo, Ran Ji; Kim, Min Hwan; Woo, Sang-Keun; Kim, Kwang Il; Lee, Tae Sup; Choi, Yang-Kyu; Kang, Joo Hyun; Lim, Sang Moo; Lee, Yong Jin

2017-01-01

Introduction: Macrophages play a key role in atherosclerotic plaque formation in atherosclerosis, but its detailed understanding has poorly investigated until now. Thus, we sought to demonstrate a noninvasive technique for macrophage tracking to atherosclerotic lesions in apolipoprotein E −/− (ApoE −/− ) mice with an imaging system based on sodium iodide symporter (NIS) gene coupled with 99m Tc-single-photon emission computed tomography (SPECT). Methods and results: Macrophage cells (RAW264.7) were stably transduced with retrovirus expressing NIS gene (RAW-NIS). In RAW-NIS cells, uptake of 125 I was higher than the parental cells. [ 18 F]FDG signals in the aorta at 30 weeks on an ApoE −/− mice with high cholesterol diet were higher (1.7 ± 0.12% injected dose (ID)) than those in control group (0.84 ± 0.06% ID). Through 99m Tc-SPECT/computed tomography (CT), in the RAW-NIS cell injected group, the 99m Tc-pertechnetate uptake in aorta was higher than control groups. However, according to atorvastatin treatment, RAW-NIS cell recruitment reduced to the aorta. Area of 99m Tc-pertechnetate uptake was positively correlated with immunostaining results against macrophage antigen (CD68). Cholesterol and low-density lipoprotein levels of atorvastatin-treated group showed lower than those of atorvastatin-untreated group, but did not reach statistical difference. Conclusions: This novel approach to tracking macrophages to atherosclerotic plaques in vivo can be applied for studies of arterosclerotic vascular disease.

Decreased expression of liver X receptor-α in macrophages infected with Chlamydia pneumoniae in human atherosclerotic arteries in situ.

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Bobryshev, Yuri V; Orekhov, Alexander N; Killingsworth, Murray C; Lu, Jinhua

2011-01-01

In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atherosclerosis is not known. In this study we examined carotid artery segments, obtained by endarterectomy, in which the presence of C. pneumoniae was confirmed by both polymerase chain reaction and immunohistochemistry. The expression of LXR-α in macrophages infected with C. pneumoniae and macrophages that were not infected was compared using a quantitative immunohistochemical analysis. The analysis revealed a 2.2-fold reduction in the expression of LXR-α in C. pneumoniae-infected cells around the lipid cores in atherosclerotic plaques. In the cytoplasm of laser-capture microdissected cells that were immunopositive for C. pneumoniae, electron microscopy demonstrated the presence of structures with the appearance of elementary, reticulate and aberrant bodies of C. pneumoniae. We conclude that LXR-α expression is reduced in C. pneumoniae-infected macrophages in human atherosclerotic lesions which supports the hypothesis that C. pneumoniae infection might suppress LXR expression in macrophages transforming into foam cells. Copyright © 2011 S. Karger AG, Basel.

The formation of labyrinths, spots and stripe patterns in a biochemical approach to cardiovascular calcification

International Nuclear Information System (INIS)

Yochelis, A; Tintut, Y; Demer, L L; Garfinkel, A

2008-01-01

Calcification and mineralization are fundamental physiological processes, yet the mechanisms of calcification, in trabecular bone and in calcified lesions in atherosclerotic calcification, are unclear. Recently, it was shown in in vitro experiments that vascular-derived mesenchymal stem cells can display self-organized calcified patterns. These patterns were attributed to activator/inhibitor dynamics in the style of Turing, with bone morphogenetic protein 2 acting as an activator, and matrix GLA protein acting as an inhibitor. Motivated by this qualitative activator-inhibitor dynamics, we employ a prototype Gierer-Meinhardt model used in the context of activator-inhibitor-based biological pattern formation. Through a detailed analysis in one and two spatial dimensions, we explore the pattern formation mechanisms of steady state patterns, including their dependence on initial conditions. These patterns range from localized holes to labyrinths and localized peaks, or in other words, from dense to sparse activator distributions (respectively). We believe that an understanding of the wide spectrum of activator-inhibitor patterns discussed here is prerequisite to their biochemical control. The mechanisms of pattern formation suggest therapeutic strategies applicable to bone formation in atherosclerotic lesions in arteries (where it is pathological) and to the regeneration of trabecular bone (recapitulating normal physiological development)

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

Energy Technology Data Exchange (ETDEWEB)

Noerenberg, Dominik [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); University of Munich - Grosshadern, Department of Clinical Radiology, Munich (Germany); Ebersberger, Hans U. [Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich (Germany); Diederichs, Gerd; Hamm, Bernd [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Botnar, Rene M. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Makowski, Marcus R. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

2016-03-15

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

International Nuclear Information System (INIS)

Noerenberg, Dominik; Ebersberger, Hans U.; Diederichs, Gerd; Hamm, Bernd; Botnar, Rene M.; Makowski, Marcus R.

2016-01-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

Anti-Atherosclerotic Effects of a Phytoestrogen-Rich Herbal Preparation in Postmenopausal Women

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Veronika A. Myasoedova

2016-08-01

7.1% in placebo recipients (NS. The differences between lipid changes in the isoflavonoid-rich herbal preparation and placebo recipients did not reach statistical significance (p > 0.05. Nevertheless, the mean cIMT progression was significantly lower in isoflavonoid-rich herbal preparation recipients as compared to the placebo group (6 μm, or <1%, versus 100 μm, or 13%; p < 0.001 for the difference. The growth of existing atherosclerotic plaques in isoflavonoid-rich herbal preparation recipients was inhibited by 1.5-fold (27% versus 41% in the placebo group. The obtained results demonstrate that the use of isoflavonoid-rich herbal preparation in postmenopausal women may suppress the formation of new atherosclerotic lesions and reduce the progression of existing ones, thus promising new drug for anti-atherosclerotic therapy. Nevertheless, further studies are required to confirm these findings.

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients

OpenAIRE

Chhibber-Goel, Jyoti; Singhal, Varsha; Bhowmik, Debaleena; Vivek, Rahul; Parakh, Neeraj; Bhargava, Balram; Sharma, Amit

2016-01-01

Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from...

Intracranial Stent Implantation for Drug Resistant Atherosclerotic Stenosis: Results of 52 Cases

International Nuclear Information System (INIS)

Kim, Kuk Seon; Hwang, Dae Hyun; Ko, Young Hwan; Kang, Ik Won; Lee, Eil Seong; Han, You Mie; Kim, In Soo; Hur, Choon Woong

2011-01-01

We evaluated the usefulness of intracranial stent implantation for treatment of drug resistant atherosclerotic stenoses. Between March 2004 and July 2007, we tried intracranial stent implantation in 49 patients with 52 lesions (anterior circulation 48 cases, posterior circulation 4 cases) who had an ischemic stroke with more than 50% of major cerebral artery stenosis. We classified the lesions by their location and morphology, analyzed the results in terms of the success rate, complication rate, and restenosis rate during the follow-up period. Intracranial stent implantation was performed successfully in 43 cases (82.7%). In eight of the nine cases, the stent implantation failure was due to the tortuosity of the target vessel. There was no major periprocedural complication. One patient showed cerebellar infarction after the procedure. Mean residual stenoses decreased from 70.2% to 13.0%. Four cases (9.3%) demonstrated in-stent restenoses and more than 50% during the mean and 25.3/month after the follow-up period. Success rate of intracranial stent implantation may improve on developing technique and more experience. Low rate of complication and restenosis suggest that we can consider intracranial stent implantation for treatment of drug resistant atherosclerotic stenoses.

Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease.

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Pasterkamp, Gerard; den Ruijter, Hester M; Libby, Peter

2017-01-01

The concept of the 'vulnerable plaque' originated from pathological observations in patients who died from acute coronary syndrome. This recognition spawned a generation of research that led to greater understanding of how complicated atherosclerotic plaques form and precipitate thrombotic events. In current practice, an increasing number of patients who survive their first event present with non-ST-segment elevation myocardial infarction (NSTEMI) rather than myocardial infarction (MI) with ST-segment elevation (STEMI). The culprit lesions that provide the pathological substrate for NSTEMI can vary considerably from the so-called 'vulnerable plaque'. The shift in clinical presentation of MI and stroke corresponds temporally to a progressive change in the characteristics of human plaques away from the supposed characteristics of vulnerability. These alterations in the structure and function of human atherosclerotic lesions might mirror the modifications that are produced in experimental plaques by lipid lowering, inspired by the vulnerable plaque construct. The shift in the clinical presentations of the acute coronary syndromes mandates a critical reassessment of the underlying mechanisms, proposed risk scores, the results and interpretation of preclinical experiments, as well as recognition of the limitations of the use of population data and samples collected before the application of current preventive interventions.

Vinpocetine attenuates lipid accumulation and atherosclerosis formation

International Nuclear Information System (INIS)

Cai, Yujun; Li, Jian-Dong; Yan, Chen

2013-01-01

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis

Vinpocetine attenuates lipid accumulation and atherosclerosis formation

Energy Technology Data Exchange (ETDEWEB)

Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

2013-05-10

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

Surgical treatment of penetrating atherosclerotic ulcer of the descending aorta

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Kovačević Pavle

2013-01-01

Full Text Available Introduction. The term “penetrating atherosclerotic ulcer” (PAU of the aorta describes the condition in which ulceration of an aortic atherosclerotic lesion penetrates the internal elastic lamina into media. PAU is a high-risk lesion due to its deleterious effects on the integrity of aortic wall, with potentially fatal outcome. Case report. A patient with intensive, sharp chest pain irradiating to the back but with no signs of myocardial ischemia on an electrocardiogram was referred to our hospital. Transthoracic echocardiography showed no pathological changes of the ascending aorta. However, multislice computed tomography (CT showed an aortic ulcer with varying degree of the subadventitial hemorrhage in the region of the thoracic aorta at the level of Th 8-9. Due to imminent rupture of the penetrating aortic ulcer, the patient was promptly prepared for surgery. A 15 cm long subadventitial hematoma was found intraoperatively in the right posterolateral aspect of the descending aorta, 5 cm above the diaphragm and 7 cm below the origin of the left subclavial artery. The affected segment of the aorta was resected, followed by an inlay aortic reconstruction with a Dacron tube graft of 24 mm. Control CT revealed satisfactory reconstruction of the descending aorta. Conclusion. PAU is a rare, but potentially fatal disease. Open surgery in patients with PAU is an effective treatment strategy, although endovascular treatment options are emerging.

Impact of cavitation on lesion formation induced by high intensity focused ultrasound

International Nuclear Information System (INIS)

Fan Pengfei; Jie Yu; Yang Xin; Tu Juan; Guo Xiasheng; Zhang Dong; Huang Pintong

2017-01-01

High intensity focused ultrasound (HIFU) has shown a great promise in noninvasive cancer therapy. The impact of acoustic cavitation on the lesion formation induced by HIFU is investigated both experimentally and theoretically in transparent protein-containing gel and ex vivo liver tissue samples. A numerical model that accounts for nonlinear acoustic propagation and heat transfer is used to simulate the lesion formation induced by the thermal effect. The results showed that lesions could be induced in the samples exposed to HIFU with various acoustic pressures and pulse lengths. The measured areas of lesions formed in the lateral direction were comparable to the simulated results, while much larger discrepancy was observed between the experimental and simulated data for the areas of longitudinal lesion cross-section. Meanwhile, a series of stripe-wiped-off B-mode pictures were obtained by using a special imaging processing method so that HIFU-induced cavitation bubble activities could be monitored in real-time and quantitatively analyzed as the functions of acoustic pressure and pulse length. The results indicated that, unlike the lateral area of HIFU-induced lesion that was less affected by the cavitation activity, the longitudinal cross-section of HIFU-induced lesion was significantly influenced by the generation of cavitation bubbles through the temperature elevation resulting from HIFU exposures. Therefore, considering the clinical safety in HIFU treatments, more attention should be paid on the lesion formation in the longitudinal direction to avoid uncontrollable variation resulting from HIFU-induced cavitation activity. (paper)

⁶⁴Cu-DOTATATE PET/MRI for detection of activated macrophages in carotid atherosclerotic plaques

DEFF Research Database (Denmark)

Pedersen, Sune Folke; Sandholt, Benjamin Vikjær; Keller, Sune Høgild

2015-01-01

OBJECTIVE: A feature of vulnerable atherosclerotic plaques of the carotid artery is high activity and abundance of lesion macrophages. There is consensus that this is of importance for plaque vulnerability, which may lead to clinical events, such as stroke and transient ischemic attack. We used p...

Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques.

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Nazanin Hakimzadeh

Full Text Available Molecular imaging of matrix metalloproteinases (MMPs may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9 with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT imaging that effectively targets atherosclerotic lesions in mice.

Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques

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Molenaar, Ger; de Waard, Vivian; Lutgens, Esther; van Eck-Smit, Berthe L. F.; de Bruin, Kora; Piek, Jan J.; Eersels, Jos L. H.; Booij, Jan; Verberne, Hein J.; Windhorst, Albert D.

2017-01-01

Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice. PMID:29190653

Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts.

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Maurovich-Horvat, Pál; Schlett, Christopher L; Alkadhi, Hatem; Nakano, Masataka; Stolzmann, Paul; Vorpahl, Marc; Scheffel, Hans; Tanaka, Atsushi; Warger, William C; Maehara, Akiko; Ma, Shixin; Kriegel, Matthias F; Kaple, Ryan K; Seifarth, Harald; Bamberg, Fabian; Mintz, Gary S; Tearney, Guillermo J; Virmani, Renu; Hoffmann, Udo

2012-11-01

To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both Padvanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, Padvanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, Padvanced coronary plaques. © RSNA, 2012

Virtual histology study of atherosclerotic plaque composition in patients with stable angina and acute phase of acute coronary syndromes without ST segment elevation

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Ivanović Miloš

2013-01-01

Full Text Available Introduction. Rupture of vulnerable atherosclerotic plaques is the cause of most acute coronary syndromes (ACS. Postmortem studies which compared stable coronary lesions and atherosclerotic plaques in patients who have died because of ACS indicated high lipid-core content as one of the major determinants of plaque vulnerability. Objective. Our primary goal was to assess the potential relations of plaque composition determined by IVUS-VH (Intravascular Ultrasound - Virtual Histology in patients with stable angina and subjects in acute phase of ACS without ST segment elevation. Methods. The study comprised of 40 patients who underwent preintervention IVUS examination. Tissue maps were reconstructed from radio frequency data using IVUS-VH software. Results. We analyzed 53 lesions in 40 patients. Stable angina was diagnosed in 24 patients (29 lesions, while acute phase of ACS without ST elevation was diagnosed in 16 patients (24 lesions. In the patients in acute phase of ACS without ST segment elevation IVUS-VH examination showed a significantly larger area of the necrotic core at the site of minimal lumen area and a larger mean of the necrotic core volume in the entire lesion comparing to stable angina subjects (1.84±0.90 mm2 vs. 0.96±0.69 mm2; p<0.001 and 20.94±15.79 mm3 vs. 11.54±14.15 mm3; p<0.05 respectively. Conclusion. IVUS-VH detected that the necrotic core was significantly larger in atherosclerotic lesions in patients in acute phase of ACS without ST elevation comparing to the stable angina subjects and that it could be considered as a marker of plaque vulnerability.

Association of CD147 genetic polymorphisms with carotid atherosclerotic plaques in a Han Chinese population with cerebral infarction.

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Ni, Tongtian; Chen, Min; Yang, Kang; Shao, Jianwei; Fu, Yi; Zhou, Weijun

2017-08-01

Given the important role of CD147 in the development of atherosclerosis, we speculated that CD147 genetic polymorphisms might influence the formation of carotid atherosclerotic plaques. The study was to investigate the association between CD147 gene polymorphisms and susceptibility to carotid atherosclerotic plaques in individuals with cerebral infarction (CI). Eight SNPs in the regulatory and coding regions of the CD147 gene were examined using polymerase chain reaction-ligase detection reaction (PCR-LDR) in DNA samples from 732 Chinese patients with CI, divided into a carotid plaque group (n=475) and a non-carotid plaque group (n=257). Significant differences were found in the genotypes and allele frequencies of the rs4919862 SNP between the carotid plaque and non-carotid plaque groups of CI patients (PCD147 was closely associated with carotid atherosclerotic plaques formation. Thus, polymorphisms of the CD147 gene may be related to the tendency for carotid atherosclerotic plaques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE-/- mice

International Nuclear Information System (INIS)

Campen, Matthew J.; Lund, Amie K.; Knuckles, Travis L.; Conklin, Daniel J.; Bishop, Barbara; Young, David; Seilkop, Steven; Seagrave, JeanClare; Reed, Matthew D.; McDonald, Jacob D.

2010-01-01

Recent epidemiological studies suggest that traffic-related air pollution may have detrimental effects on cardiovascular health. Previous studies reveal that gasoline emissions can induce several enzyme pathways involved in the formation and development of atherosclerotic plaques. As a direct comparison, the present study examined the impact of diesel engine emissions on these pathways, and further examined the effects on vascular lesion pathology. Apolipoprotein E-null mice were simultaneously placed on a high-fat chow diet and exposed to four concentrations, plus a high concentration exposure with particulates (PM) removed by filtration, of diesel emissions for 6 h/day for 50 days. Aortas were subsequently assayed for alterations in matrix metalloproteinase-9, endothelin-1, and several other biomarkers. Diesel induced dose-related alterations in gene markers of vascular remodeling and aortic lipid peroxidation; filtration of PM did not significantly alter these vascular responses, indicating that the gaseous portion of the exhaust was a principal driver. Immunohistochemical analysis of aortic leaflet sections revealed no net increase in lesion area, but a significant decrease in lipid-rich regions and increasing trends in macrophage accumulation and collagen content, suggesting that plaques were advanced to a more fragile, potentially more vulnerable state by diesel exhaust exposure. Combined with previous studies, these results indicate that whole emissions from mobile sources may have a significant role in promoting chronic vascular disease.

Low TLR7 gene expression in atherosclerotic plaques is associated with major adverse cardio- and cerebrovascular events

DEFF Research Database (Denmark)

Karadimou, Glykeria; Folkersen, Lasse; Berg, Martin

2016-01-01

Aims: Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome an...

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients.

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Chhibber-Goel, Jyoti; Singhal, Varsha; Bhowmik, Debaleena; Vivek, Rahul; Parakh, Neeraj; Bhargava, Balram; Sharma, Amit

2016-01-01

Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from coronary artery disease patients. In this study, we present meta-analysis from published studies that have independently investigated the presence of bacteria within atherosclerotic plaque samples in coronary artery disease patients. Data were collated from 63 studies covering 1791 patients spread over a decade. Our analysis confirms the presence of 23 oral commensal bacteria, either individually or in co-existence, within atherosclerotic plaques in patients undergoing carotid endarterectomy, catheter-based atherectomy, or similar procedures. Of these 23 bacteria, 5 ( Campylobacter rectus , Porphyromonas gingivalis , Porphyromonas endodontalis , Prevotella intermedia , Prevotella nigrescens ) are unique to coronary plaques, while the other 18 are additionally present in non-cardiac organs, and associate with over 30 non-cardiac disorders. We have cataloged the wide spectrum of proteins secreted by above atherosclerotic plaque-associated bacteria, and discuss their possible roles during microbial migration via the bloodstream. We also highlight the prevalence of specific poly-microbial communities within atherosclerotic plaques. This work provides a resource whose immediate implication is the necessity to systematically catalog landscapes of atherosclerotic plaque-associated oral commensal bacteria in human patient populations.

Inflammation in renal atherosclerotic disease.

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Udani, Suneel M; Dieter, Robert S

2008-07-01

The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

Formation of 3D cholesterol crystals from 2D nucleation sites in lipid bilayer membranes: implications for atherosclerosis.

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Varsano, Neta; Fargion, Iael; Wolf, Sharon G; Leiserowitz, Leslie; Addadi, Lia

2015-02-04

Atherosclerosis is the major precursor of cardiovascular disease. The formation of cholesterol crystals in atherosclerotic plaques is associated with the onset of acute pathology. The cholesterol crystals induce physical injury in the plaque core, promoting cell apoptosis and triggering an increased inflammatory response. Herein we address the question of how cholesterol crystal formation occurs in atherosclerosis. We demonstrate that three-dimensional (3D) cholesterol crystals can undergo directed nucleation from bilayer membranes containing two-dimensional (2D) cholesterol crystalline domains. We studied crystal formation on supported lipid bilayers loaded with exogenous cholesterol and labeled using a monoclonal antibody that specifically recognizes ordered cholesterol arrays. Our findings show that 3D crystals are formed exclusively on the bilayer regions where there are segregated 2D cholesterol crystalline domains and that they form on the domains. This study has potentially significant implications for our understanding of the crucial step in the mechanism by which atherosclerotic lesions form.

Anti-atherosclerotic effects of konjac

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Hidekatsu Yanai

2015-04-01

Full Text Available Definition: The Konjac plant comes from the genus Amorphophallus. Japanese food uses Konjac cake. Konjac contains almost no calories and a great amount of dietary fiber. Here, we reviewed possible anti-atherosclerotic effects of konjac, using the search Pubmed ®. Konjac ingestion is likely beneficially associated with obesity, blood pressure, lipid and glucose metabolism. However, evidence is lacking on the relationship between konjac ingestion and development of atherosclerotic diseases. To more fully understand the anti-atherosclerotic effects of konjac, future studies, preferably with larger numbers of subjects, will be performed.

Cross-reacting antibacterial auto-antibodies are produced within coronary atherosclerotic plaques of acute coronary syndrome patients.

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Filippo Canducci

Full Text Available Coronary atherosclerosis, the main condition predisposing to acute myocardial infarction, has an inflammatory component caused by stimuli that are yet unknown. We molecularly investigated the nature of the immune response within human coronary lesion in four coronary plaques obtained by endoluminal atherectomy from four patients. We constructed phage-display libraries containing the IgG1/kappa antibody fragments produced by B-lymphocytes present in each plaque. By immunoaffinity, we selected from these libraries a monoclonal antibody, arbitrarily named Fab7816, able to react both with coronary and carotid atherosclerotic tissue samples. We also demonstrated by confocal microscopy that this monoclonal antibody recognized human transgelin type 1, a cytoskeleton protein involved in atherogenesis, and that it co-localized with fibrocyte-like cells transgelin+, CD68+, CD45+ in human sections of coronary and carotid plaques. In vitro fibrocytes obtained by differentiating CD14+ cells isolated from peripheral blood mononuclear cells also interacted with Fab7816, thus supporting the hypothesis of a specific recognition of fibrocytes into the atherosclerotic lesions. Interestingly, the same antibody, cross-reacted with the outer membrane proteins of Proteus mirabilis and Klebsiella pneumoniae (and possibly with homologous proteins of other enterobacteriaceae present in the microbiota. From all the other three libraries, we were able to clone, by immunoaffinity selection, human monoclonal antibodies cross-reacting with bacterial outer membrane proteins and with transgelin. These findings demonstrated that in human atherosclerotic plaques a local cross-reactive immune response takes place.

Protective role of parnaparin in reducing systemic inflammation and atherosclerotic plaque formation in ApoE-/- mice.

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Artico, Marco; Riganò, Rachele; Buttari, Brigitta; Profumo, Elisabetta; Ionta, Brunella; Bosco, Sandro; Rasile, Manuela; Bianchi, Enrica; Bruno, Moira; Fumagalli, Lorenzo

2011-04-01

Atherosclerosis is a degenerative disease whose role in the onset and development of cardiovascular pathologies and complications is of importance. Due to its silent but progressive development, and considering the endothelial, immunological and inflammatory processes that are involved in its clinical course, this still relatively unknown pathological condition has been and continues to be a matter of investigation worldwide. Our experience with previous studies on atherosclerosis led us to investigate the possible influence of a low molecular weight heparin (LMWH) - Parnaparin® on the development and clinical course of atherosclerosis in double knock-out laboratory animals (ApoE-/- mice). Our experiments demonstrated a possible role of Parnaparin (PNP) in the control of atherogenic disease. In fact, in treated mice vs. untreated ones, PNP reduced the number and the size of atherosclerotic lesions in the aortic wall, as well as the development of liver steatosis, which was massive in untreated animals and moderate in treated ones. These preliminary observations require further clinical studies, but demonstrate a possible role of Parnaparin in the control of the development and clinical evolution of atherosclerosis and liver steatosis in laboratory animals.

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

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Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang; Jiang, Zhi-xin; Chen, Xiao-min

2015-01-01

Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

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Shuang-shuang Wang

Full Text Available Formation and progression of atherosclerotic vulnerable plaque (VP is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model.Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP group (n = 10/group and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9 in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6 mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively.Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis

Collateral circulation alters downstream hemodynamic stress caused by intracranial atherosclerotic stenosis.

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Liu, Xin; Dornbos, David; Pu, Yuehua; Leng, Xinyi; Song, Ligang; Jia, Baixue; Pan, Yuesong; Wang, David; Miao, Zhongrong; Wang, Yilong; Liu, Liping; Wang, Yongjun

2017-06-01

Fractional flow reserve (FFR) accurately predicts the degree of stenosis and is now widely used to identify clinically significant severe coronary artery lesions. In the current study, we utilized a similar indicator, fractional flow (FF), to determine the hemodynamic impact of symptomatic intracranial atherosclerotic stenosis (ICAS) and to assess the correlation of FF with the severity of stenosis and collateral circulation. Patients with symptomatic ICAS (70-99% stenosis) confirmed on digital subtraction angiography (DSA) were consecutively recruited. FF was obtained during DSA examination with the use of pressure sensors and was measured as a ratio, comparing measurements distal to an ICAS lesion (Pd) and within the aorta (Pa). The degree of leptomeningeal collateralization was graded from zero (absent) to four (complete compensatory). The correlation between FF, anatomical stenosis, and collateral status was then analyzed. Twenty-five patients with a mean age of 55.6 years were analyzed. The median percentage of stenosis and median FF were 82.3 and 0.68%, respectively. Eleven patients were found to have poor collateralization (grade 0-2), and fourteen patients were identified with good collateral circulation (grade 3-4). Overall, the hemodynamic impact of an atherosclerotic lesions worsened (decreased FF) as the percentage of stenosis increased, although this did not reach statistical significance (r = -0.398, p = 0.06). However, the status of collateralization significantly altered this correlation, worsening the hemodynamic impact in patients with poor collateral circulation (r = -0.677, p = 0.032). There was no difference in patients with good collateral circulation (r = -0.279, p = 0.356). An anatomically severe (70-99%) symptomatic ICAS lesion may generate significant hemodynamic stress downstream as assessed by the indicator FF, particularly in patients with poor collateral circulation. Further, good collateralization may mitigate this

Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development.

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Amanda C Foks

Full Text Available OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. METHODS AND RESULTS: TIGIT was upregulated on CD4(+ T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/- mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. CONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells.

Anti-atherosclerotic effects of tomatoes

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Hidekatsu Yanai

2017-06-01

Full Text Available Tomatoes are rich in lycopene, which causes the red coloring of tomatoes. Several reports have suggested lycopene plays a role in the prevention of cardiovascular diseases. In this study, we systematically reviewed the interventional studies using tomatoes or tomato products to understandtheanti-atherosclerotic effects of the tomatoas a functional food. We found that a significantnumber of interventional studies reportedtheanti-atherosclerotic effects of tomatoes, includinganti-obesity effects, hypotensiveeffects, improvement of lipid/glucose metabolismand endothelial function, anti-oxidative and anti-inflammatory effect, and anti-platelet effect; however, the anti-platelet effect was disagreed uponby some studies. Furthermore, we discoveredcooking methods significantlyaffect anti-atherosclerotic effects of tomatoes.

[Mechanistic modelling allows to assess pathways of DNA lesion interactions underlying chromosome aberration formation].

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Eĭdel'man, Iu A; Slanina, S V; Sal'nikov, I V; Andreev, S G

2012-12-01

The knowledge of radiation-induced chromosomal aberration (CA) mechanisms is required in many fields of radiation genetics, radiation biology, biodosimetry, etc. However, these mechanisms are yet to be quantitatively characterised. One of the reasons is that the relationships between primary lesions of DNA/chromatin/chromosomes and dose-response curves for CA are unknown because the pathways of lesion interactions in an interphase nucleus are currently inaccessible for direct experimental observation. This article aims for the comparative analysis of two principally different scenarios of formation of simple and complex interchromosomal exchange aberrations: by lesion interactions at chromosome territories' surface vs. in the whole space of the nucleus. The analysis was based on quantitative mechanistic modelling of different levels of structures and processes involved in CA formation: chromosome structure in an interphase nucleus, induction, repair and interactions of DNA lesions. It was shown that the restricted diffusion of chromosomal loci, predicted by computational modelling of chromosome organization, results in lesion interactions in the whole space of the nucleus being impossible. At the same time, predicted features of subchromosomal dynamics agrees well with in vivo observations and does not contradict the mechanism of CA formation at the surface of chromosome territories. On the other hand, the "surface mechanism" of CA formation, despite having certain qualities, proved to be insufficient to explain high frequency of complex exchange aberrations observed by mFISH technique. The alternative mechanism, CA formation on nuclear centres is expected to be sufficient to explain frequent complex exchanges.

In vivo determination of arterial collagen synthesis in atherosclerotic rabbits

International Nuclear Information System (INIS)

Opsahl, W.P.; DeLuca, D.J.; Ehrhart, L.A.

1986-01-01

Collagen and non-collagen protein synthesis rates were determined in vivo in tissues from rabbits fed a control or atherogenic diet supplemented with 2% peanut oil and 0.25% cholesterol for 4 months. Rabbits received a bolus intravenous injection of L-[ 3 H]-proline (1.0 mCi/kg) and unlabeled L-proline (7 mmoles/kg) in 0.9% NaCl. Plasma proline specific activity decreased only 20% over 5 hr and was similar to the specific activity of free proline in tissues. Thoracic aortas from atherosclerotic rabbits exhibited raised plaques covering at least 75% of the surface. Thoracic intima plus a portion of the media (TIM) was separated from the remaining media plus adventitia (TMA). Dry delipidated weight, total collagen content, and collagen as a percent of dry weight were increased significantly in the TIM of atherosclerotic rabbits. Collagen synthesis rates and collagen synthesis as a percent of total protein synthesis were likewise increased both in the TIM and in the abdominal aortas. No differences from controls either in collagen content or collagen synthesis rates were observed in the TMA, lung or skin. These results demonstrate for the first time in vivo that formation of atherosclerotic plaques is associated with increased rates of collagen synthesis. Furthermore, as previously observed with incubations in vitro, collagen synthesis was elevated to a greater extent than noncollagen protein synthesis in atherosclerotic aortas from rabbits fed cholesterol plus peanut oil

A salmon protein hydrolysate exerts lipid-independent anti-atherosclerotic activity in ApoE-deficient mice.

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Cinzia Parolini

Full Text Available Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo E(-/- mice were divided into two groups and fed a high-fat diet with or without 5% (w/w SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in the 12 apoE(-/- mice fed 5% SPH for 12 weeks compared to the 12 casein-fed control mice. Immunohistochemical characterization of atherosclerotic lesions in aortic sinus displayed no differences in plaque composition between mice fed SPH compared to controls. However, reduced mRNA level of Icam1 in the aortic arch was found. The plasma content of arachidonic acid (C20:4n-6 and oleic acid (C18:1n-9 were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1β, IL-6, TNF-α and GM-CSF, whereas plasma cholesterol and triacylglycerols (TAG were unchanged, accompanied by unchanged mitochondrial fatty acid oxidation and acyl-CoA:cholesterol acyltransferase (ACAT-activity. These data show that a 5% (w/w SPH diet reduces atherosclerosis in apoE(-/- mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids or fatty acids.

Uremia does not affect neointima formation in mice

DEFF Research Database (Denmark)

Aarup, Annemarie; Nielsen, Carsten H; Bisgaard, Line S

2017-01-01

Atherosclerotic cardiovascular disease is a major complication of chronic kidney disease (CKD). CKD leads to uremia, which modulates the phenotype of aortic smooth muscle cells (SMCs). Phenotypic modulation of SMCs plays a key role in accelerating atherosclerosis. We investigated the hypothesis...... that uremia potentiates neointima formation in response to vascular injury in mice. Carotid wire injury was performed on C57BL/6 wt and apolipoprotein E knockout (Apoe-/-) mice two weeks after induction of uremia by 5/6 nephrectomy. Wire injury led to neointima formation and downregulation of genes encoding...... classical SMC markers (i.e., myocardin, α-smooth muscle actin, SM22-alpha, and smooth muscle myosin heavy chain) in both wt and Apoe-/-mice. Contrary to our expectations, uremia did not potentiate neointima formation, nor did it affect intimal lesion composition as judged from magnetic resonance imaging...

Intracranial Atherosclerotic Disease

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Maria Khan

2011-01-01

Full Text Available Intracranial atherosclerotic disease (ICAD is the most common proximate mechanism of ischemic stroke worldwide. Approximately half of those affected are Asians. For diagnosis of ICAD, intra-arterial angiography is the gold standard to identify extent of stenosis. However, noninvasive techniques including transcranial ultrasound and MRA are now emerging as reliable modalities to exclude moderate to severe (50%–99% stenosis. Little is known about measures for primary prevention of the disease. In terms of secondary prevention of stroke due to intracranial atherosclerotic stenosis, aspirin continues to be the preferred antiplatelet agent although clopidogrel along with aspirin has shown promise in the acute phase. Among Asians, cilostazol has shown a favorable effect on symptomatic stenosis and is of benefit in terms of fewer bleeds. Moreover, aggressive risk factor management alone and in combination with dual antiplatelets been shown to be most effective in this group of patients. Interventional trials on intracranial atherosclerotic stenosis have so far only been carried out among Caucasians and have not yielded consistent results. Since the Asian population is known to be preferentially effected, focused trials need to be performed to establish treatment modalities that are most effective in this population.

Self-gated CINE MRI for combined contrast-enhanced imaging and wall-stiffness measurements of murine aortic atherosclerotic lesions

NARCIS (Netherlands)

den Adel, Brigit; van der Graaf, Linda M.; Strijkers, Gustav J.; Lamb, Hildo J.; Poelmann, Robert E.; van der Weerd, Louise

2013-01-01

High-resolution contrast-enhanced imaging of the murine atherosclerotic vessel wall is difficult due to unpredictable flow artifacts, motion of the thin artery wall and problems with flow suppression in the presence of a circulating contrast agent. We applied a 2D-FLASH retrospective-gated CINE MRI

Microvessel Density But Not Neoangiogenesis Is Associated with (18)F-FDG Uptake in Human Atherosclerotic Carotid Plaques

DEFF Research Database (Denmark)

Pedersen, Sune Folke; Græbe, Martin; Hag, Anne Mette Fisker

2011-01-01

Introduction: The vulnerable atherosclerotic lesion exhibits the proliferation of neovessels and inflammation. The imaging modality 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18FDG-PET) is considered for the identification of vulnerable plaques. Purpose: The purpose of this study...... was to compare the gene expression of neoangiogenesis and vulnerability-associated genes with 18FDG uptake in patients undergoing carotid endarterectomy. Procedures: Human atherosclerotic carotid artery plaques from symptomatic patients were used for gene expression analysis by quantitative PCR of vascular...... analysis was compared with 18FDG-PET. Results: VEGF and integrin aVß3 gene expression did not correlate with 18FDG uptake, whereas CD34 gene expression exhibited an inverse correlation with 18FDG uptake. Additionally, we established that markers of vulnerability were correlated with 18FDG uptake...

Endovascular revascularization for aortoiliac atherosclerotic disease

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Aggarwal V

2016-03-01

Full Text Available Vikas Aggarwal,1 Stephen W Waldo,2,3 Ehrin J Armstrong2,3 1Prairie Heart Institute, St John's Hospital, Springfield, IL, 2Section of Cardiology, Denver Veterans Affairs Medical Center, 3Section of Cardiology, University of Colorado, Aurora, CO, USA Abstract: Atherosclerotic iliac artery disease is increasingly being treated with endovascular techniques. A number of new stent technologies can be utilized with high long-term patency, including self-expanding stents, balloon-expandable stents, and covered stents, but comparative data on these stent types and in more complex lesions are lacking. This article provides a review of currently available iliac stent technologies, as well as complex procedural aspects of iliac artery interventions, including approaches to the treatment of iliac bifurcation disease, long segment occlusions, choice of stent type, and treatment of iliac artery in-stent restenosis. Keywords: peripheral artery disease, iliac artery, balloon expandable stent, self expanding stent, covered stent, claudication, endovascular

The relationship between serum paraoxonase levels and carotid atherosclerotic plaque formation in Alzheimer's patients.

Science.gov (United States)

Arslan, Ayşe; Tüzün, Fatma Aykan; Arslan, Harun; Demir, Halit; Tamer, Sibel; Demir, Canan; Tasin, Muhterem

Low paraoxonase 1 (PON1) activity and carotid atherosclerosis have been suggested to be important risk factors for dementia. However, the studies to date could not fully clarify the relationship between PON1, carotid atherosclerosis and dementia. The present study aimed to measure carotid atherosclerosis and PON1 activity in Alzheimer's Disease and to evaluate the relationship between them. The study included 25 Alzheimer's patients and 25 control subjects, for a total of 50 individuals. The study measured the serum PON1 activity and other biochemical parameters and carotid atherosclerotic plaque values of the participants. The mean paraoxonase activity (31.06±2.31U/L) was significantly lower in the Alzheimer's group compared to the control group (59.05±7.05U/L) (Phomocystein level was higher in the patient group (22.15±7.05) compared to the control group (13.30±3.32). In conclusion, our findings show inverse association between PON1 activity and carotid atherosclerosis in Alzheimer patients: the lower the PON1 activity the more progressed the atherosclerotic process in AD. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Vascular brain lesions, brain atrophy, and cognitive decline. The Second Manifestations of ARTerial diseased-Magnetic Resonance (SMART-MR) study

NARCIS (Netherlands)

Kooistra, M.; Geerlings, M.I.; van der Graaf, Y.; Mali, W.P.T.M.; Vincken, K.L.; Kappelle, L.J.; Muller, M.; Biessels, G.J.

2014-01-01

We examined the association between brain atrophy and vascular brain lesions (i.e., white matter lesions [WMLs] or brain infarcts), alone or in combination, with decline in memory and executive functioning over 4 years of follow-up in 448 patients (57 ± 9.5 years) with symptomatic atherosclerotic

DNA radio-induced tandem lesions: formation, introduction in oligonucleotides and repair

International Nuclear Information System (INIS)

Bourdat, Anne-Gaelle

2000-01-01

Cell killing induced by excited photosensitizers, ionizing radiation or radiomimetic drugs can not be only explained by the formation of single DNA lesions. Thus, multiply damaged sites, are likely to have harmful biological consequences. One example of tandem base damage induced by ".OH radical in X-irradiated aqueous solution of DNA oligomers is N-(2-deoxy-β-D-erythro-pentofuranosyl)-formyl-amine (dβF)/8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). In order to investigate the biological significance of such a tandem lesion, both 8-oxodGuo and dβF were introduced in synthetic oligonucleotides at vicinal positions using the solid phase phosphoramidite method with the 'Pac phosphoramidite' chemistry. The purity of the synthetic DNA fragments and the integrity of modified nucleosides was confirmed using different complementary techniques: HPLC, PAGE, ESI MS, MALDI-TOF MS and capillary electrophoresis. Using the above synthetic substrates, investigations were carried out in order to determine the substrate specificity and the excision mechanism of three glycosylases involved in the base excision repair pathway: endonuclease III, Fpg and yOggl. Both tandem lesions were substrates for the BER enzymes. However, the tandem lesion are not completely excised by the repair enzymes. The rates of excision as inferred from the determination of the ratios of Vm/Km Michaelis kinetics constants were not found to be significantly affected by the presence of the tandem lesions. MALDI-TOF mass spectrometry was used in order to gain insights into mechanistic aspects of oligonucleotide cleavage by the BER enzymes. During in vitro DNA synthesis by Taq DNA polymerase, Klenow fragment exo- and DNA polymerase β, tandem base damage were found to block the progression of the enzymes. Finally, the level of tandem base damage in the DNA exposed to γ-ray using the liquid chromatography coupled to electro-spray ionization tandem mass spectrometry was determined. Both dβF-8-oxodGuo and 8

Angiomatous lesion and delayed cyst formation after gamma knife surgery for intracranial meningioma: case report and review of literatures.

Science.gov (United States)

Liu, Zhiyong; He, Min; Chen, Hongxu; Liu, Yi; Li, Qiang; Li, Lin; Li, Jin; Chen, Haifeng; Xu, Jianguo

2015-01-01

Gamma Knife has become a major therapeutic method for intracranial meningiomas, vascular malformations and schwannomas with exact effect. In recent years an increasing number of delayed complications after Gamma Knife surgery have been reported, such as secondary tumors, cystic changes or cyst formation. But angiomatous lesion and delayed cyst formation after Gamma Knife for intracranial lesion has rarely been reported. Here we report the first case of angiomatous lesion and delayed cyst formation following Gamma Knife for intracranial meningioma and discuss its pathogenesis.

Transcriptional profiling uncovers a network of cholesterol-responsive atherosclerosis target genes.

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Josefin Skogsberg

2008-03-01

Full Text Available Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr(-/-Apo(100/100Mttp(flox/flox Mx1-Cre. Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies.

Myeloid protein tyrosine phosphatase 1B (PTP1B deficiency protects against atherosclerotic plaque formation in the ApoE−/− mouse model of atherosclerosis with alterations in IL10/AMPKα pathway

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D. Thompson

2017-08-01

Conclusions: Here we demonstrate that inhibiting the activity of PTP1B specifically in myeloid lineage cells protects against atherosclerotic plaque formation, under atherogenic conditions, in an ApoE−/− mouse model of atherosclerosis. Our findings suggest for the first time that macrophage PTP1B targeting could be a therapeutic target for atherosclerosis treatment and reduction of CVD risk.

Chemical risk factors responsible for the formation of wedge-shaped lesions

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Perić Dejan

2015-01-01

Full Text Available Introduction: Non-carious tooth substances loss pose a major health problem of a modern man. The literature often collectively describes all non-carious lesions and is therefore difficult to compare results obtained by different authors. Chemical factors are one of the predisposing factors responsible for the formation of wedge-shaped erosions. Aim: Examination of chemical risk factors as one of the predisposing causes responsible for the formation of wedge-shaped lesions. Method: We examined 62 patients with wedge-shaped erosions (mean age 45.52 ± 12.03 years, 58.1% of men and 60 patients without erosions in the control group (mean age 34.40 ± 9.28 years, 60% men . The entire examination was completed by using a questionnaire at the Dental Clinic of the University of Pristina - Kosovska Mitrovica. salivary pH was measured by the pH meter. Results: The results show that the wedge-shaped lesions often occur equally in both men and women. Considerably often it might appear in older people but can also occur in teenagers. Patients with wedge-shaped erosion have increased acidity of saliva, a heightened sense of acid in the mouth and consume a lot more carbonated drinks compared to patients without erosions. Conclusion: Wedge-shaped lesions are more common in people older than 40 years. Taking into account the results obtained in this study it can be concluded that the chemical risk factors truly fall within the predisposing factors that may be responsible for the creation of wedge-shaped erosions.

HDL mimetic CER-001 targets atherosclerotic plaques in patients.

Science.gov (United States)

Zheng, Kang He; van der Valk, Fleur M; Smits, Loek P; Sandberg, Mara; Dasseux, Jean-Louis; Baron, Rudi; Barbaras, Ronald; Keyserling, Constance; Coolen, Bram F; Nederveen, Aart J; Verberne, Hein J; Nell, Thijs E; Vugts, Danielle J; Duivenvoorden, Raphaël; Fayad, Zahi A; Mulder, Willem J M; van Dongen, Guus A M S; Stroes, Erik S G

2016-08-01

Infusion of high-density lipoprotein (HDL) mimetics aimed at reducing atherosclerotic burden has led to equivocal results, which may relate in part to the inability of HDL mimetics to adequately reach atherosclerotic lesions in humans. This study evaluated delivery of recombinant human apolipoprotein A-I (apoA-I) containing HDL mimetic CER-001 in carotid plaques in patients. CER-001 was radiolabeled with the long-lived positron emitter zirconium-89 ((89)Zr) to enable positron emission tomography with computed tomography (PET/CT) imaging. Eight patients with atherosclerotic carotid artery disease (>50% stenosis) received a single infusion of unlabeled CER-001 (3 mg/kg), co-administered with 10 mg of (89)Zr-labeled CER-001 (18 MBq). Serial PET/CT imaging and contrast enhanced-magnetic resonance imaging (CE-MRI) were performed to evaluate targeted delivery of CER-001. One hour after infusion, mean plasma apoA-I levels increased by 9.9 mg/dL (p = 0.026), with a concomitant relative increase in the plasma cholesterol efflux capacity of 13.8% (p CER-001 expressed as target-to-background ratio (TBRmax) increased significantly 24 h after infusion, and remained increased up to 48 h (TBRmax t = 10 min: 0.98; t = 24 h: 1.14 (p = 0.001); t = 48 h: 1.12 (p = 0.007)). TBRmax was higher in plaque compared with non-plaque segments (1.18 vs. 1.05; p CER-001 increases plasma apoA-I concentration and plasma cholesterol efflux capacity. Our data support the concept that CER-001 targets plaque regions in patients, which correlates with plaque contrast enhancement. These clinical findings may also guide future nanomedicine development using HDL particles for drug delivery in atherosclerosis. Netherlands Trial Registry - NTR5178. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5178. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs

DEFF Research Database (Denmark)

Jacobsen, Kevin; Lund, Marie Bek; Shim, Jeong

2017-01-01

Fibrous cap smooth muscle cells (SMCs) protect atherosclerotic lesions from rupturing and causing thrombosis, while other plaque SMCs may have detrimental roles in plaque development. To gain insight into recruitment of different plaque SMCs, we mapped their clonal architecture in aggregation...... in the cap and heterogeneous ACTA2– SMCs in the plaque interior, including chondrocyte-like cells and cells with intracellular lipid and crystalline material. Fibrous cap SMCs were invariably arranged in endothelium-aligned clonal sheets, confirming results in the aggregation chimeras. Analysis of the clonal...

Upregulation of proinflammatory genes in skin lesions may be the cause of keloid formation (Review)

Science.gov (United States)

DONG, XIANGLIN; MAO, SHAOLIN; WEN, HAO

2013-01-01

It was previously demonstrated that the main cause behind keloid formation may be keloid fibroblast abnormalities, which are closely associated with the microenvironment of the keloid lesion. The post-traumatic and chronic inflammation of the keloid lesion area suggest that inflammatory mediators play an important role in the keloid microenvironment and are crucial for keloid fibroblast abnormalities. In this study, we hypothesized that the mechanism underlying keloid formation may involve the continuous upregulation of proinflammatory gene expression in keloid lesions. This hypothesis may explain the inflammatory response, invasive growth and recurrence following resection of keloids, as well as the selective localization of keloids in specific parts of a patient’s body and the differences in localization among different patients. PMID:24649037

Current techniques for the investigation of vulnerable atherosclerotic plaques

International Nuclear Information System (INIS)

Riou, L.; Broisat, A.; Fagret, D.; Ghezzi, C.

2005-01-01

Atherosclerosis is the single most important contributor to cardiovascular diseases, the leading cause of death in industrialized countries. Atherosclerosis complications such as vulnerable coronary plaque rupture or erosion result in acute coronary events, i.e. myocardial infarction and sudden death. Vulnerable plaques initially develop eccentrically without impeding on the vessel lumen and are therefore not detectable using angiography. New techniques for the investigation of vulnerable plaques are needed to identify and treat vulnerable patients. Invasive techniques require the use of intracoronary probes and are thereby not applicable to large populations of patients. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are the most promising invasive modalities. They provide morphological data that could potentially be associated with a more functional approach such as thermography, elasto-graphy, or spectroscopy, Non-invasive techniques are better suited for studying larger populations of patients. Computed tomography is currently used for calcium scoring, but the biological meaning and the prognostic value of this index remain to be fully determined. Non-invasive coronary magnetic resonance imaging (MRI) faces numerous technical challenges, and it essentially provides morphological data. Molecular nuclear imaging offers a great sensitivity and the ability to provide metabolic data about atherosclerotic lesions. New potential tracers of vulnerable plaques are currently being evaluated. Nuclear Medicine should therefore play a major role in the future as a non invasive imaging modality for the assessment of vulnerable atherosclerotic plaques. (author)

3D Fiber Orientation in Atherosclerotic Carotid Plaques

NARCIS (Netherlands)

A.C. Akyildiz (Ali); C.-K. Chai (Chen-Ket); C.W.J. Oomens (Cees); A. van der Lugt (Aad); F.P.T. Baaijens (Frank); G.J. Strijkers (Gustav); F.J.H. Gijsen (Frank)

2017-01-01

textabstractAtherosclerotic plaque rupture is the primary trigger of fatal cardiovascular events. Fibrillar collagen in atherosclerotic plaques and their directionality are anticipated to play a crucial role in plaque rupture. This study aimed assessing 3D fiber orientations and architecture in

Pathologic features of lower extremity arterial lesions in diabetes mellitus:an analysis of 162 patients

International Nuclear Information System (INIS)

Guo Xiangjiang; Zhang Jiwei

2010-01-01

Objective: To investigate the angiographic manifestations of lower extremity atherosclerotic occlusion in patients with diabetes mellitus. Methods: The angiographic findings of lower extremity in 162 patients with diabetes mellitus were retrospectively analyzed. (1) The arteries of lower extremity were divided into the following four segments: iliac, femoral, popliteal and crural artery. The involvements of these arteries were documented. (2) Based on the lesion's number, location, nature (stricture or occlusion) and length ( 5 cm), the diabetic arterial diseases were categorized. Results: (1) Of 162 diabetic lower limbs, multiple segmental lesions were seen in 131, superficial femoral arterial lesions in 130, and crural arterial lesions in 139, of which 130 arterial lesions had at least two below-the-knee arteries being involved. (2) Based on segmental angiographic classification, a total of 660 vascular lesions were detected, including stricture lesions (33.8%) and occlusive lesions (66.2%). Of the 437 occlusions, 70.5% were located in below-the-knee arteries, and most of which were longer than 10 cm and located in anterior and posterior tibial arteries, while only a few peroneal arteries were involved (P < 0.0001). One hundred and fifty-two lesions were detected in superficial femoral arteries, of which 49 (31.2%) were located at the origin of the superficial femoral artery and 56 (35.7) were in the adductor canal hiatus. Conclusion: The main feature of peripheral arterial disease of lower extremity caused by diabetes mellitus is multi-level atherosclerotic occlusion, the superficial femoral and the crural arteries are most likely to be involved. The lesions of superficial femoral artery are often located at the arterial origin and in the adductor canal hiatus, while the deep femoral artery and the femoral artery are less involved. Long occlusive lesions are more prevalent in crural arteries, especially in anterior and posterior tibial arteries. (J Intervent

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

International Nuclear Information System (INIS)

Kinoshita, Hiroyuki; Matsumura, Takeshi; Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko; Takeya, Motohiro; Nishikawa, Takeshi; Araki, Eiichi

2013-01-01

Highlights: ► We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ► Apocynin prevented atherosclerotic lesion formation. ► Apocynin suppressed ROS production in aorta and in macrophages. ► Apocynin suppressed cytokine expression and cell proliferation in macrophages. ► Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE –/– ) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE –/– mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE –/– mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

Energy Technology Data Exchange (ETDEWEB)

Kinoshita, Hiroyuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Takeya, Motohiro [Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)

2013-02-08

Highlights: ► We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ► Apocynin prevented atherosclerotic lesion formation. ► Apocynin suppressed ROS production in aorta and in macrophages. ► Apocynin suppressed cytokine expression and cell proliferation in macrophages. ► Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE{sup –/–}) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE{sup –/–} mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE{sup –/–} mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.

CT Determination of Fractional Flow Reserve in Coronary Lesions

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Mester András

2016-12-01

Full Text Available Invasively determined fractional flow reserve (FFR represents the gold-standard method for the functional evaluation of coronary lesions. Coronary computed tomography angiography (CCTA provides characterization of the coronary anatomy, with important morphological information on the atherosclerotic plaques, but does not offer a hemodynamic evaluation of coronary artery lesions. CT evaluation of FFR (FFRCT is a new noninvasive diagnostic method, which provides anatomical and functional assessment of the whole coronary tree, based on computational techniques, with no more radiation or hyperemic agent administration compared with routine CCTA. Recent studies demonstrated the safety and accuracy of FFRCT and its therapeutic use and cost benefits in real-world clinical use.

Large mobile thrombus in non-atherosclerotic thoracic aorta as the source of peripheral arterial embolism

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Brkovic Zoran

2005-11-01

Full Text Available Abstract The presence of thrombi in the atherosclerotic and/or aneurysmatic aorta with peripheral arterial embolism is a common scenario. Thrombus formation in a morphologically normal aorta, however, is a rare event. A 50 years old woman was admitted to the mergency department for pain, coldness, and anesthesia in the the left foot. She had a 25 years history of cigarette smoking, a history of postmenopausal hormone replacement therapy (HRT, hypercholesterolemia and hyperfibrinogenemia. An extensive serologic survey for hypercoagulability, including antiphospholipid antibodies, and vasculitis disorders was negative. Transesophageal echocardiography revealed a large, pedunculated and hypermobile thrombus attached to the aortic wall 5 cm distal of the left subclavian artery. The patient was admitted to the surgery department, where a 15 cm long fresh, parietal thrombus could be removed from the aorta showing no macroscopic wall lesions or any other morphologic abnormalities. This case report demonstrates the possibility of evolving a large, pedunculated thrombus in a morphologically intact aorta in a postmenopausal woman with thrombogenic conditions such as hyperfibrinogenemia, hypercholesterolemia, smoking and HRT. For these patients, profiling the individual risk and weighing the benefits against the potential risks is warranted before prescribing HRT.

Relationship Between Endothelial Wall Shear Stress and High-Risk Atherosclerotic Plaque Characteristics for Identification of Coronary Lesions That Cause Ischemia: A Direct Comparison With Fractional Flow Reserve.

Science.gov (United States)

Han, Donghee; Starikov, Anna; Ó Hartaigh, Bríain; Gransar, Heidi; Kolli, Kranthi K; Lee, Ji Hyun; Rizvi, Asim; Baskaran, Lohendran; Schulman-Marcus, Joshua; Lin, Fay Y; Min, James K

2016-12-19

Wall shear stress (WSS) is an established predictor of coronary atherosclerosis progression. Prior studies have reported that high WSS has been associated with high-risk atherosclerotic plaque characteristics (APCs). WSS and APCs are quantifiable by coronary computed tomography angiography, but the relationship of coronary lesion ischemia-evaluated by fractional flow reserve-to WSS and APCs has not been examined. WSS measures were obtained from 100 evaluable patients who underwent coronary computed tomography angiography and invasive coronary angiography with fractional flow reserve. Patients were categorized according to tertiles of mean WSS values defined as low, intermediate, and high. Coronary ischemia was defined as fractional flow reserve ≤0.80. Stenosis severity was determined by minimal luminal diameter. APCs were defined as positive remodeling, low attenuation plaque, and spotty calcification. The likelihood of having positive remodeling and low-attenuation plaque was greater in the high WSS group compared with the low WSS group after adjusting for minimal luminal diameter (odds ratio for positive remodeling: 2.54, 95% CI 1.12-5.77; odds ratio for low-attenuation plaque: 2.68, 95% CI 1.02-7.06; both Prelationship was observed between WSS and fractional flow reserve when adjusting for either minimal luminal diameter or APCs. WSS displayed no incremental benefit above stenosis severity and APCs for detecting lesions that caused ischemia (area under the curve for stenosis and APCs: 0.87, 95% CI 0.81-0.93; area under the curve for stenosis, APCs, and WSS: 0.88, 95% CI 0.82-0.93; P=0.30 for difference). High WSS is associated with APCs independent of stenosis severity. WSS provided no added value beyond stenosis severity and APCs for detecting lesions with significant ischemia. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

[68Ga]Pentixafor-PET/MRI for the detection of Chemokine receptor 4 expression in atherosclerotic plaques

International Nuclear Information System (INIS)

Li, Xiang; Heber, Daniel; Leike, Tatjana; Hacker, Marcus; Haug, Alexander R.; Beitzke, Dietrich; Loewe, Christian; Lu, Xia; Zhang, Xiaoli; Wei, Yongxiang; Mitterhauser, Markus; Wadsak, Wolfgang; Kropf, Saskia; Wester, Hans J.

2018-01-01

The expression of chemokine receptor type 4 (CXCR4) was found co-localized with macrophages on the atherosclerotic vessel wall and participated in the initial emigration of leukocytes. Gallium-68 [ 68 Ga]Pentixafor has recently been introduced for the imaging of atherosclerosis by targeting CXCR4. We sought to evaluate human atherosclerotic lesions using [ 68 Ga]Pentixafor PET/MRI. Thirty-eight oncology patients underwent [ 68 Ga]Pentixafor PET/MR imaging at baseline. Maximum standardized uptake values (SUV max ) were derived from hot lesions in seven arterial segments and target-to-blood ratios (TBR) were calculated. ANOVA post-hoc and paired t test were performed for statistical comparison, Spearman's correlation coefficient between uptake ratios and cardiovascular risk factors were assessed. The reproducibility of [ 68 Ga]Pentixafor PET/MRI was assessed in seven patients with a follow-up examination by Pearson's regression and Bland-Altman plots analysis. Thirty-four of 38 patients showed 611 focal [ 68 Ga]Pentixafor uptake that followed the contours of the large arteries. Both prevalence and mean TBR max were highest in the descending aorta. There were significantly higher TBR values found in men (1.9 ± 0.3) as compared to women (1.7 ± 0.2; p < 0.05). Patients with mean TBR max > 1.7 showed a significantly higher incidence of diabetes, hypertension hypercholesterolemia and history of cardiovascular disease than patients with mean TBR max ≤ 1.7. [ 68 Ga]Pentixafor uptake showed a good reproducibility (r = 0.6, p < 0.01), and there was no difference between the mean TBR max values of plaque lesions (TBR baseline 1.8 ± 0.3 vs TBR follow-up 1.8 ± 0.3) (p = 0.9). Patients with high arterial uptake showed increased incidence of cardiovascular risk factors, suggesting a potential role of [ 68 Ga]Pentixafor in characterization of atherosclerosis. (orig.)

Modulation of growth control mechanisms critical to atherogenesis

NARCIS (Netherlands)

Zwijsen, R.M.L.

1992-01-01

The principal lesion characteristic of atherosclerosis is the plaque. This lesion mainly consists of smooth muscle cells, connective matrix and large amounts of extracellular lipids. Smooth muscle cell hyperplasia is an integral event in atherosclerotic plaque formation and the resultant

Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

International Nuclear Information System (INIS)

Fukuda, Kazuki; Matsumura, Takeshi; Senokuchi, Takafumi; Ishii, Norio; Kinoshita, Hiroyuki; Yamada, Sarie; Murakami, Saiko; Nakao, Saya; Motoshima, Hiroyuki; Kondo, Tatsuya; Kukidome, Daisuke; Kawasaki, Shuji; Kawada, Teruo; Nishikawa, Takeshi; Araki, Eiichi

2015-01-01

Highlights: • Statins induce PPARγ activation in vascular smooth muscle cells. • Statin-induced PPARγ activation is mediated by COX-2 expression. • Statins suppress cell migration and proliferation in vascular smooth muscle cells. • Statins inhibit LPS-induced inflammatory responses by PPARγ activation. • Fluvastatin suppress the progression of atherosclerosis and induces PPARγ activation in the aorta of apoE-deficient mice. - Abstract: The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe −/− mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe −/− mice. In conclusion, statins mediate anti-atherogenic effects through PPAR�

Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits

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Tsutsui, H.; Tomoike, H.; Nakamura, M.

1990-01-01

Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using [ 14 C]antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of [ 14 C]antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements

Impact of positive and negative lesion site remodeling on clinical outcomes: insights from PROSPECT.

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Inaba, Shinji; Mintz, Gary S; Farhat, Naim Z; Fajadet, Jean; Dudek, Dariusz; Marzocchi, Antonio; Templin, Barry; Weisz, Giora; Xu, Ke; de Bruyne, Bernard; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

2014-01-01

This study investigated coronary artery remodeling patterns associated with clinical outcomes. In the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area (MLA) ≤4 mm(2), a plaque burden ≥70%, and a IVUS-virtual histology (VH) thin-cap fibroatheroma (TCFA), but not lesion site remodeling. Overall, 697 consecutive patients with an acute coronary syndrome were enrolled and underwent 3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The remodeling index (RI) was calculated as the external elastic membrane area at the MLA site divided by the average of the proximal and distal reference external elastic membrane areas. First, one third of the patients were randomly selected to determine RI cutoffs related to NCL MACE (development cohort). Receiver-operating characteristic analysis showed that there were 2 separate cut points that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve = 0.663). These cut points were used to define negative remodeling as an RI 1.00. Second, we used the remaining two-thirds of patients to validate these cut points with respect to lesion morphology and clinical outcomes (validation cohort). Kaplan-Meier curve analysis in the validation cohort showed that NCL MACE occurred more frequent (and equally) in negative and positive remodeling lesions compared with intermediate remodeling lesions. In this cohort, negative remodeling lesions had the smallest MLA, positive remodeling lesions had the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic cores, was most common in negatively remodeling lesions. The present study showed the novel concept that positive and negative lesion site remodeling was

The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

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Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

2013-11-01

Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

Cardiovascular risk factors and collateral artery formation.

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de Groot, D; Pasterkamp, G; Hoefer, I E

2009-12-01

Arterial lumen narrowing and vascular occlusion is the actual cause of morbidity and mortality in atherosclerotic disease. Collateral artery formation (arteriogenesis) refers to an active remodelling of non-functional vascular anastomoses to functional collateral arteries, capable to bypass the site of obstruction and preserve the tissue that is jeopardized by ischaemia. Hemodynamic forces such as shear stress and wall stress play a pivotal role in collateral artery formation, accompanied by the expression of various cytokines and invasion of circulating leucocytes. Arteriogenesis hence represents an important compensatory mechanism for atherosclerotic vessel occlusion. As arteriogenesis mostly occurs when lumen narrowing by atherosclerotic plaques takes place, presence of cardiovascular risk factors (e.g. hypertension, hypercholesterolaemia and diabetes) is highly likely. Risk factors for atherosclerotic disease affect collateral artery growth directly and indirectly by altering hemodynamic forces or influencing cellular function and proliferation. Adequate collateralization varies significantly among atherosclerotic patients, some profit from the presence of extensive collateral networks, whereas others do not. Cardiovascular risk factors could increase the risk of adverse cardiovascular events in certain patients because of the reduced protection through an alternative vascular network. Likewise, drugs primarily thought to control cardiovascular risk factors might contribute or counteract collateral artery growth. This review summarizes current knowledge on the influence of cardiovascular risk factors and the effects of cardiovascular medication on the development of collateral vessels in experimental and clinical studies.

Evaluation of five DNA extraction methods for purification of DNA from atherosclerotic tissue and estimation of prevalence of Chlamydia pneumoniae in tissue from a Danish population undergoing vascular repair

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Lindholt Jes S

2003-09-01

Full Text Available Abstract Background To date PCR detection of Chlamydia pneumoniae DNA in atherosclerotic lesions from Danish patients has been unsuccessful. To establish whether non-detection was caused by a suboptimal DNA extraction method, we tested five different DNA extraction methods for purification of DNA from atherosclerotic tissue. Results The five different DNA extraction methods were tested on homogenate of atherosclerotic tissue spiked with C. pneumoniae DNA or EB, on pure C. pneumoniae DNA samples and on whole C. pneumoniae EB. Recovery of DNA was measured with a C. pneumoniae-specific quantitative real-time PCR. A DNA extraction method based on DNA-binding to spin columns with a silica-gel membrane (DNeasy Tissue kit showed the highest recovery rate for the tissue samples and pure DNA samples. However, an automated extraction method based on magnetic glass particles (MagNA Pure performed best on intact EB and atherosclerotic tissue spiked with EB. The DNeasy Tissue kit and MagNA Pure methods and the highly sensitive real-time PCR were subsequently used on 78 atherosclerotic tissue samples from Danish patients undergoing vascular repair. None of the samples were positive for C. pneumoniae DNA. The atherosclerotic samples were tested for inhibition by spiking with two different, known amounts of C. pneumoniae DNA and no samples showed inhibition. Conclusion As a highly sensitive PCR method and an optimised DNA extraction method were used, non-detection in atherosclerotic tissue from the Danish population was probably not caused by use of inappropriate methods. However, more samples may need to be analysed per patient to be completely certain on this. Possible methodological and epidemiological reasons for non-detection of C. pneumoniae DNA in atherosclerotic tissue from the Danish population are discussed. Further testing of DNA extraction methods is needed as this study has shown considerable intra- and inter-method variation in DNA recovery.

Primary Self-Expandable Nitinol Stent Placement in Focal Lesions of Infrarenal Abdominal Aorta: Long Term Results

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Lastovickova, Jarmila; Peregrin, Jan H.

2008-01-01

Purpose. To evaluate the technical and clinical success, safety and long term results of percutaneous transluminal angioplasty/self-expandable nitinol stent placement of infrarenal abdominal aorta focal lesions. Materials and Methods. Eighteen patients underwent PTA of focal atherosclerotic occlusive disease of distal abdominal aorta. Two symptomatic occlusions and 16 stenoses in 10 male and 8 female patients (mean age 68.2 years) were treated with primary self-expandable nitinol stent placement. Results. Primary self-expandable nitinol stent placement was technically successful in all 18 procedures; clinical success was achieved in 100% of patients. No complications associated with the procedure occurred. During the 49.4 months of mean follow up (range 3-96, 4 months) all treated aortic segments remained patent. Conclusions. Endovascular treatment (primary self-expandable nitinol stent placement) of focal atherosclerotic lesions of distal abdominal aorta is a safe method with excellent primary technical and clinical success rates and favourable Long term results

Chronic administration of mitochondrion-targeted peptide SS-31 prevents atherosclerotic development in ApoE knockout mice fed Western diet.

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Meng Zhang

Full Text Available Oxidative stress and inflammatory factors are deeply involved in progression of atherosclerosis. Mitochondrion-targeted peptide SS-31, selectively targeting to mitochondrial inner membrane reacting with cardiolipin, has been reported to inhibit ROS generation and mitigate inflammation. The present study was designed to investigate whether SS-31 could suppress the development of atherosclerosis in vivo.Male ApoE-/- mice (8 weeks old fed with Western diet were treated with normal saline or SS-31 (1 mg/kg/d or 3 mg/kg/d through subcutaneous injection for 12 weeks. Oil Red O staining was performed to evaluate area and sizes of the plaques. DHE staining and immunohistochemical staining of 8-OHDG was performed to assess the oxidative stress. The aorta ATP contents were assessed by the ATP bioluminescence assay kit. Immunohistochemical staining of CD68 and α-SMA and Masson's trichrome staining were performed to evaluate the composition of atherosclerotic plaque. Biochemical assays were performed to determine the protein level and activity of superoxide dismutase (SOD. The levels of CD36, LOX-1 and ABCA1 were immunohistochemically and biochemically determined to evaluate the cholesterol transport in aorta and peritoneal macrophages. Inflammatory factors, including ICAM-1, MCP-1, IL-6 and CRP in serum, were detected through ELISA.SS-31 administration reduced the area and sizes of western diet-induced atherosclerotic plaques and changed the composition of the plaques in ApoE-/- mice. Oxidative stress was suppressed, as evidenced by the reduced DHE stain, down-regulated 8-OHDG expression, and increased SOD activity after chronic SS-31 administration. Moreover, systemic inflammation was ameliorated as seen by decreasing serum ICAM-1, MCP-1, and IL-6 levels. Most importantly, SS-31 administration inhibited cholesterol influx by down-regulating expression of CD36 and LOX-1 to prevent lipid accumulation to further suppress the foam cell formation and

ORAL EXPOSURE TO ACROLEIN EXACERBATES ATHEROSCLEROSIS IN APO E-NULL MICE

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Srivastava, Sanjay; Sithu, Srinivas D.; Vladykovskaya, Elena; Haberzettl, Petra; Hoetker, David J.; Siddiqui, Maqsood A.; Conklin, Daniel J.; D'Souza, Stanley E.; Bhatnagar, Aruni

2011-01-01

Background Acrolein is a dietary aldehyde that is present in high concentrations in alcoholic beverages and foods including cheese, donuts and coffee. It is also abundant in tobacco smoke, automobile exhaust and industrial waste and is generated in vivo during inflammation and oxidative stress. Objectives The goal of this study was to examine the effects of dietary acrolein on atherosclerosis. Methods Eight-week old male apoE-null mice were gavage-fed acrolein (2.5 mg/kg/day) for 8 weeks. Atherosclerotic lesion formation and composition and plasma lipids and platelet factor 4 (PF4) levels were measured. Effects of acrolein and PF4 on endothelial cell function was measured in vitro. Results Acrolein feeding increased the concentration of cholesterol in the plasma. NMR analysis of the lipoproteins showed that acrolein feeding increased the abundance of small and medium VLDL particles. Acrolein feeding also increased atherosclerotic lesion formation in the aortic valve and the aortic arch. Immunohistochemical analysis showed increased macrophage accumulation in the lesions of acrolein-fed mice. Plasma PF4 levels and accumulation of PF4 in atherosclerotic lesions was increased in the acrolein-fed mice. Incubation of endothelial cells with the plasma of acrolein-fed mice augmented transmigration of monocytic cells, which was abolished by anti-PF4 antibody treatment. Conclusions Dietary exposure to acrolein exacerbates atherosclerosis in apoE-null mice. Consumption of foods and beverages rich in unsaturated aldehydes such as acrolein may be a contributing factor to the progression of atherosclerotic lesions. PMID:21371710

Ursodeoxycholic acid impairs atherogenesis and promotes plaque regression by cholesterol crystal dissolution in mice.

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Bode, Niklas; Grebe, Alena; Kerksiek, Anja; Lütjohann, Dieter; Werner, Nikos; Nickenig, Georg; Latz, Eicke; Zimmer, Sebastian

2016-09-09

Atherosclerosis is a chronic inflammatory disease driven primarily by a continuous retention of cholesterol within the subendothelial space where it precipitates to form cholesterol crystals (CC). These CC trigger a complex inflammatory response through activation of the NLRP3 inflammasome and promote lesion development. Here we examined whether increasing cholesterol solubility with ursodeoxycholic acid (UDCA) affects vascular CC formation and ultimately atherosclerotic lesion development. UDCA mediated intracellular CC dissolution in macrophages and reduced IL-1β production. In ApoE(-/-) mice, UDCA treatment not only impaired atherosclerotic plaque development but also mediated regression of established vascular lesions. Importantly, mice treated with UDCA had decreased CC-depositions in atherosclerotic plaques compared to controls. Together, our data demonstrate that UDCA impaired CC and NLRP3 dependent inflammation by increasing cholesterol solubility and diminished atherosclerosis in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) with concurrent contralateral vertebral atherosclerotic diseases in 88 patients treated with the intracranial stenting

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Wang, Zi-Liang [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China); Gao, Bu-Lang [Department of Medical Research Shijiazhuang First Hospital, Hebei Medical University (China); Li, Tian-Xiao, E-mail: litianxiaod@163.com [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China); Cai, Dong-Yang; Zhu, Liang-Fu; Bai, Wei-Xing; Xue, Jiang-Yu; Li, Zhao-Shuo [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China)

2015-09-15

Highlights: • Symptomatic vertebral artery stenosis can be treated with intracranial stenting. • Stenting for intracranial vertebral artery stenosis is safe and effective. • Stenting for intracranial vertebral artery stenosis can prevent long-term stroke. - Abstract: Purpose: To investigate the safety, effect and instent restenosis rate of Wingspan stenting in treating patients with intracranial vertebral artery atherosclerotic stenosis (70–99%) concurrent with contralateral vertebral artery atherosclerotic diseases. Materials and methods: Eighty-eight patients with severe symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) combined with contralateral vertebral artery atherosclerotic diseases were treated with the Wingpsan stent. All the baseline, cerebral angiography, success rate, perioperative complications, clinical and imaging follow-up data were prospectively analyzed. Results: The success rate of stenting was 100%, and the mean stenotic rate was reduced from prestenting (84.9 ± 6.8)% to poststenting (17.2 ± 5.9)%. The perioperative stroke rate was 1.1%. Among eighty patients (90.9%) with clinical follow-up 8-62 months (mean 29.3 ± 17.2) poststenting, five (6.3%) had posterior circulation TIA only, three (3.8%) had mild stroke in the posterior circulation but recovered completely, and another five patients greater than 70 years old died of non-ischemic stroke. Imaging follow-up in 46 patients (52.3%) 5–54 months (mean 9.9 ± 9.9) following stenting revealed instent restenosis in 12 patients (26.1%) including 7 (58.3%) symptomatic restenosis. Age and residual stenosis were the two factors to significantly (P < 0.05) affect instent restenosis. Conclusion: Wingspan stenting in the intracranial vertebral artery atherosclerotic stenosis combined with contralateral vertebral artery atherosclerotic diseases has a low perioperative stroke rate and a good preventive effect on long-term ischemic stroke, but the instent restenosis

Cardiovascular magnetic resonance in carotid atherosclerotic disease

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Chen Huijun

2009-12-01

Full Text Available Abstract Atherosclerosis is a chronic, progressive, inflammatory disease affecting many vascular beds. Disease progression leads to acute cardiovascular events such as myocardial infarction, stroke and death. The diseased carotid alone is responsible for one third of the 700,000 new or recurrent strokes occurring yearly in the United States. Imaging plays an important role in the management of atherosclerosis, and cardiovascular magnetic resonance (CMR of the carotid vessel wall is one promising modality in the evaluation of patients with carotid atherosclerotic disease. Advances in carotid vessel wall CMR allow comprehensive assessment of morphology inside the wall, contributing substantial disease-specific information beyond luminal stenosis. Although carotid vessel wall CMR has not been widely used to screen for carotid atherosclerotic disease, many trials support its potential for this indication. This review summarizes the current state of knowledge regarding carotid vessel wall CMR and its potential clinical application for management of carotid atherosclerotic disease.

The Natural Compound Dansameum Reduces foam Cell Formation by Downregulating CD36 and Peroxisome Proliferator-activated Receptor-gamma; Expression.

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Park, Kang-Seo; Ahn, Sang Hyun; Lee, Kang Pa; Park, Sun-Young; Cheon, Jin Hong; Choi, Jun-Yong; Kim, Kibong

2018-01-01

Atherosclerosis-induced vascular disorders are major causes of death in most western countries. During the development of atherosclerotic lesions, foam cell formation is essential and formed through the expression of CD36 and the peroxisome proliferator-activated receptor gamma (PPAR-γ). To investigate whether dansameum extract (DSE) could show anti-atherosclerotic effect through down-regulating cellular redox state including CD36 and PARP-γ expression in oxidative low-density lipoprotein (oxLDL)-treated RAW264.7 cells and on differentiated foam cells in ApoE Knockout (ApoE-/-) mice. The Korean polyherbal medicine DSE was prepared from three plants in the following proportions: 40 g of Salvia miltiorrhiza root, 4 g of Amomumxanthioides fruit, and 4 g of Santalum album lignum. The immunohistochemistry and reverse transcription-polymerase chain reaction was used for analysis of protein and mRNA involved in foam cell formation. We first showed that effects of DSE on foam cell formation in both oxLDL-induced RAW264.7 cells and in blood vessels from apolipoprotein E deficientApoE-/- mice with high fat diet-fed. DSE treatment significantly reduced the expression of CD36 and PPAR-γ in oxLDL-stimulated RAW264.7 cells and ApoE-/-mice, in the latter case by regulating heme oxygenase-1. Furthermore, DSE treatment also reduced cellular lipid content in vitro and in vivo experiments. Our data suggest that DSE may have anti-atherosclerotic properties through regulating foam cell formation. Dansameum extract (DSE) Regulates the expression of CD36 and peroxisome proliferator-activated receptor gamma in oxidative low-density lipoprotein-stimulated RAW264.7 Cells and ApoE Knockout (ApoE Knockout [ApoE-/-]) miceDSE Regulates Cholesterol Levels in the Serum of ApoE-deficient (ApoE-/-) miceDSE Reduced the Formation of Foam Cells by Regulating heme oxygenase-1 in ApoE-/- mice with high fat diet-fed. Abbreviations used: DSE: Dansameum extract, PPAR-γ: Peroxisome proliferator

Serial changes of coronary atherosclerotic plaque: Assessment with 64-slice multi-detector computed tomography

International Nuclear Information System (INIS)

Kim, Eun Young; Kang, Doo Kyoung; Sun, Joo Sung; Choi, So Yeon

2013-01-01

Evaluate the progression of coronary atherosclerotic plaque during follow-up, and its association with cardiovascular risk factors. Fifty-six atherosclerotic patients with plaque were enrolled in this retrospective study. Patient's plaque was detected on repeat 64-slice multidetector CT scans with a mean interval of 25 ± 10 months changes in calcified and non-calcified plaque volumes and cardiovascular risk factors were assessed over time. Absolute and relative changes in plaque volume were compared, and the association between rapid progression and cardiovascular risk factors was determined. Diameter of the stenosis, length, calcified and non-calcified lesion plaque volumes increased significantly on follow-up CT. Absolute and relative annual changes in plaque volumes were significantly greater in non-calcified plaque (median, 22.7 mm 3 , 90.4%) than in calcified plaque (median, 0.7 mm 3 , 0%). Obesity, smoking, hypertension, hypercholesterolemia, and low high-density lipoprotein were significant predictors of progression of non-calcified plaque. Progression of calcified plaque was not associated with any cardiovascular risk factors. Coronary plaque volume increased significantly on follow-up CT. The rate of progression is related to non-calcified plaque than to calcified plaque. Cardiovascular risk factors are independently associated with the rapid progression of non-calcified plaque volume, but not associated with the progression of calcified plaque.

Preventive effect of dipeptidyl peptidase-4 inhibitor on atherosclerosis is mainly attributable to incretin's actions in nondiabetic and diabetic apolipoprotein E-null mice.

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Michishige Terasaki

Full Text Available AIM: Several recent reports have revealed that dipeptidyl peptidase (DPP-4 inhibitors have suppressive effects on atherosclerosis in apolipoprotein E-null (Apoe (-/- mice. It remains to be seen, however, whether this effect stems from increased levels of the two active incretins, glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic polypeptide (GIP. METHODS: Nontreated Apoe (-/- mice, streptozotocin-induced diabetic Apoe (-/- mice, and db/db diabetic mice were administered the DPP-4 inhibitor vildagliptin in drinking water and co-infused with either saline, the GLP-1 receptor blocker, exendin(9-39, the GIP receptor blocker, (Pro(3GIP, or both via osmotic minipumps for 4 weeks. Aortic atherosclerosis and oxidized low-density lipoprotein-induced foam cell formation in exudate peritoneal macrophages were determined. RESULTS: Vildagliptin increased plasma GLP-1 and GIP levels without affecting food intake, body weight, blood pressure, or plasma lipid profile in any of the animals tested, though it reduced HbA1c in the diabetic mice. Diabetic Apoe (-/- mice exhibited further-progressed atherosclerotic lesions and foam cell formation compared with nondiabetic counterparts. Nondiabetic and diabetic Apoe (-/- mice showed a comparable response to vildagliptin, namely, remarkable suppression of atherosclerotic lesions with macrophage accumulation and foam cell formation in peritoneal macrophages. Exendin(9-39 or (Pro(3GIP partially attenuated the vildagliptin-induced suppression of atherosclerosis. The two blockers in combination abolished the anti-atherosclerotic effect of vildagliptin in nondiabetic mice but only partly attenuated it in diabetic mice. Vildagliptin suppressed macrophage foam cell formation in nondiabetic and diabetic mice, and this suppressive effect was abolished by infusions with exendin(9-39+(Pro(3GIP. Incubation of DPP-4 or vildagliptin in vitro had no effect on macrophage foam cell formation. CONCLUSIONS: Vildagliptin

Bone marrow endothelial progenitors in atherosclerotic plaque resolution

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Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Barlic-Dicen, Jana

2013-01-01

Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, and deposition of low-density lipoprotein in the vascular wall are the main inducers of atherosclerosis, which manifests itself as arterial lesions or plaques. Some plaques become thrombosis-prone and rupture, causing acute myocardial infarction or stroke. Lowering plasma cholesterol through the use of statins is the primary intervention against atherosclerosis. Treatment with statins slows progression of atherosclerosis but can only support limited plaque regression. Partially regressed plaques continue to pose a serious threat due to their remaining potential to rupture. Thus, new interventions inducing complete reversal of atherosclerosis are being sought. Implementation of new therapies will require clear understanding of the mechanisms driving plaque resolution. In this Commentary, we highlight the role of bone marrow endothelial progenitors in atherosclerotic plaque regression and discuss how regenerative cell-based interventions could be used in combination with plasma lipid-lowering to induce plaque reversal in order to prevent and/or reduce adverse cardiovascular events. PMID:23538778

[Adrenal hormones in the formation of atherosclerotic precursors in adolescents with primary arterial hypertension].

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Bogmat, L F

1993-01-01

The components of blood lipid spectrum (total cholesterol, triglycerides and high density lipoprotein cholesterol) were studied in 131 adolescents (12-18 years old) with primary arterial hypertension at various levels of adrenal hormones (hydrocortisone and aldosterone) and blood plasma renin activity. The optimal ratio of lipid components in blood was detected if concentrations of adrenal hormones and blood plasma renin activity were low. Hyperfunction of the adrenal cortex in teen-agers contributed both to the development of hypertension and to atherosclerotic changes in vessels. This suggests that definite forms of hypertension occurred in adults, with specific impairments in the metabolism of blood serum lipids, were developed during the juvenile age.

Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture.

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Bobryshev, Y V; Killingsworth, M C; Lord, R S A; Grabs, A J

2008-10-01

Plaque rupture is the most common type of plaque complication and leads to acute ischaemic events such as myocardial infarction and stroke. Calcification has been suggested as a possible indicator of plaque instability. Although the role of matrix vesicles in the initial stages of arterial calcification has been recognized, no studies have yet been carried out to examine a possible role of matrix vesicles in plaque destabilization. Tissue specimens selected for the present study represented carotid specimens obtained from patients undergoing carotid endarterectomy. Serial frozen cross-sections of the tissue specimens were cut and mounted on glass slides. The thickness of the fibrous cap (FCT) in each advanced atherosclerotic lesion, containing a well developed lipid/necrotic core, was measured at its narrowest sites in sets of serial sections. According to established criteria, atherosclerotic plaque specimens were histologically subdivided into two groups: vulnerable plaques with thin fibrous caps (FCT <100 microm) and presumably stable plaques, in which fibrous caps were thicker than 100 microm. Twenty-four carotid plaques (12 vulnerable and 12 presumably stable plaques) were collected for the present analysis of matrix vesicles in fibrous caps. In order to provide a sufficient number of representative areas from each plaque, laser capture microdissection (LCM) was carried out. The quantification of matrix vesicles in ultrathin sections of vulnerable and stable plaques revealed that the numbers of matrix vesicles were significantly higher in fibrous caps of vulnerable plaques than those in stable plaques (8.908+0.544 versus 6.208+0.467 matrix vesicles per 1.92 microm2 standard area; P= 0.0002). Electron microscopy combined with X-ray elemental microanalysis showed that some matrix vesicles in atherosclerotic plaques were undergoing calcification and were characterized by a high content of calcium and phosphorus. The percentage of calcified matrix vesicles

[68Ga]Pentixafor-PET/MRI for the detection of Chemokine receptor 4 expression in atherosclerotic plaques

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Li, Xiang; Heber, Daniel; Leike, Tatjana; Hacker, Marcus; Haug, Alexander R. [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Beitzke, Dietrich; Loewe, Christian [Medical University of Vienna, Division of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Lu, Xia; Zhang, Xiaoli; Wei, Yongxiang [Capital Medical University, Department of Nuclear Medicine, Beijing Anzhen Hospital, Beijing (China); Mitterhauser, Markus [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Ludwig Boltzmann Institute Applied Diagnostics, Vienna (Austria); Wadsak, Wolfgang [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); CBmed, Center for Biomarker Research in Medicine, Graz (Austria); Kropf, Saskia [Scintomics GmbH, Fuerstenfeldbruck (Germany); Wester, Hans J. [Technische Universitaet Muenchen, Department of Radiopharmaceutical Chemistry, Garching (Germany)

2018-04-15

The expression of chemokine receptor type 4 (CXCR4) was found co-localized with macrophages on the atherosclerotic vessel wall and participated in the initial emigration of leukocytes. Gallium-68 [{sup 68}Ga]Pentixafor has recently been introduced for the imaging of atherosclerosis by targeting CXCR4. We sought to evaluate human atherosclerotic lesions using [{sup 68}Ga]Pentixafor PET/MRI. Thirty-eight oncology patients underwent [{sup 68}Ga]Pentixafor PET/MR imaging at baseline. Maximum standardized uptake values (SUV{sub max}) were derived from hot lesions in seven arterial segments and target-to-blood ratios (TBR) were calculated. ANOVA post-hoc and paired t test were performed for statistical comparison, Spearman's correlation coefficient between uptake ratios and cardiovascular risk factors were assessed. The reproducibility of [{sup 68}Ga]Pentixafor PET/MRI was assessed in seven patients with a follow-up examination by Pearson's regression and Bland-Altman plots analysis. Thirty-four of 38 patients showed 611 focal [{sup 68}Ga]Pentixafor uptake that followed the contours of the large arteries. Both prevalence and mean TBR{sub max} were highest in the descending aorta. There were significantly higher TBR values found in men (1.9 ± 0.3) as compared to women (1.7 ± 0.2; p < 0.05). Patients with mean TBR{sub max} > 1.7 showed a significantly higher incidence of diabetes, hypertension hypercholesterolemia and history of cardiovascular disease than patients with mean TBR{sub max} ≤ 1.7. [{sup 68}Ga]Pentixafor uptake showed a good reproducibility (r = 0.6, p < 0.01), and there was no difference between the mean TBR{sub max} values of plaque lesions (TBR{sub baseline}1.8 ± 0.3 vs TBR{sub follow-up}1.8 ± 0.3) (p = 0.9). Patients with high arterial uptake showed increased incidence of cardiovascular risk factors, suggesting a potential role of [{sup 68}Ga]Pentixafor in characterization of atherosclerosis. (orig.)

Characterization of HSP27 phosphorylation sites in human atherosclerotic plaque secretome

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Durán, Mari-Carmen; Boeri-Erba, Elisabetta; Mohammed, Shabaz

2007-01-01

spectrometry (MS). Among the identified proteins, two isoforms of heat shock protein 27 (HSP27), a protein recently described as a potential biomarker of atherosclerosis, were detected. However, the putative mechanisms in which HSP27 isoforms could be involved in the atherosclerotic process are unknown. Thus......, the role that phosphorylated HSP27 could play in the atherosclerotic process is actually under study. The present work shows the strategies employed to characterize the phosphorylation in the HSP27 secreted by atheroma plaque samples. The application of liquid chromatography tandem mass spectrometry (MS......-lymphocytes). These interactions can be mediated by proteins secreted from these cells, which therefore exert an important role in the atherosclerotic process. We recently described a novel strategy for the characterization of the human atherosclerotic plaque secretome, combining two-dimensional gel electrophoresis and mass...

Cryotherapy increases features of plaque stability in atherosclerotic rabbits.

Science.gov (United States)

Verheye, Stefan; Roth, Lynn; De Meyer, Inge; Van Hove, Cor E; Nahon, Daniel; Santoianni, Domenic; Yianni, John; Martinet, Wim; Buchbinder, Maurice; De Meyer, Guido R Y

2016-08-20

In the last 10 years, cryotherapy has been investigated as a new technology to treat vascular disease. The efficiency of cryotherapy in stabilising atherosclerotic plaques has never been described. The purpose of the present study was to evaluate the effect of catheter-based cryotherapy on atherosclerotic plaque composition in a rabbit model of atherosclerosis. Twenty-four New Zealand white rabbits were fed a 0.3% cholesterol-supplemented diet for 24 weeks. At two predefined sites of the atherosclerotic thoracic aorta, catheter-based cryotherapy, applying either single-dose, double-dose cryotherapy or control inflation, was performed after randomisation. Rabbits were continued on a cholesterol-supplemented diet for one day (acute) or four weeks (chronic). One day after cryotherapy, apoptotic cell death of smooth muscle cells (SMCs) and endothelial cells (ECs) was observed, whereas macrophages were unaffected. Four weeks later, the amount of SMCs was restored, the EC layer was regenerated, and a subendothelial macrophage-free layer was formed, indicative of a more stable plaque. In addition, both the thickness and the type I collagen content of the fibrous cap were increased. The present study demonstrated that cryotherapy is feasible and appears to stabilise atherosclerotic plaques in a rabbit model.

Monitoring of arterial wall remodelling in atherosclerotic rabbits with a magnetic resonance imaging contrast agent binding to matrix metalloproteinases

Science.gov (United States)

Hyafil, Fabien; Vucic, Esad; Cornily, Jean-Christophe; Sharma, Rahul; Amirbekian, Vardan; Blackwell, Francis; Lancelot, Eric; Corot, Claire; Fuster, Valentin; Galis, Zorina S.; Feldman, Laurent J.; Fayad, Zahi A.

2011-01-01

Aims P947 is a gadolinium-based magnetic resonance imaging (MRI) contrast agent with high affinity for several matrix metalloproteinases (MMPs) involved in arterial wall remodelling. We tested whether the intensity of enhancement detected in vivo in the arterial wall with P947 and MRI correlates with actual tissue MMP-related enzymatic activity measured in a rabbit atherosclerotic model subjected to dietary manipulations. Methods and results Aortas of 15 rabbits in which atherosclerotic lesions were induced by balloon angioplasty and 4 months of hypercholesterolaemic diet were imaged at ‘baseline’ with P947-enhanced MRI. Atherosclerotic rabbits were divided into three groups: five rabbits were sacrificed (‘baseline’ group); five rabbits continued to be fed a lipid-supplemented diet (‘high-fat’ group); and five rabbits were switched from atherogenic to a purified chow diet (‘low-fat’ group). Four months later, a second P947-enhanced MRI was acquired in the 10 remaining rabbits. A significantly lower signal was detected in the aortic wall of rabbits from the ‘low-fat’ group as compared with rabbits from the ‘high-fat’ group (21 ± 6 vs. 46 ± 3%, respectively; P = 0.04). Such differences were not detected with the contrast agent P1135, which lacks the MMP-specific peptide sequence. In addition, the intensity of aortic wall enhancement detected with MRI after injection of P947 strongly correlated with actual MMP-2 gelatinolytic activity measured in corresponding aortic segments using zymography (r = 0.87). Conclusion P947-enhanced MRI can distinguish dietary-induced variations in MMP-related enzymatic activity within plaques in an experimental atherosclerotic model, supporting its utility as a clinical imaging tool for in vivo detection of arterial wall remodelling. PMID:21118852

Immunochemical detection of food-derived polyphenols in the aorta: macrophages as a major target underlying the anti-atherosclerotic activity of polyphenols.

Science.gov (United States)

Kawai, Yoshichika

2011-01-01

It has been suggested that polyphenol-rich diets decrease the risk of cardiovascular diseases. Although studies of the bioavailability of polyphenols, particularly their absorption and metabolism, have been reported recently, the tissue and cellular distributions underlying their biological mechanisms remain unknown. It is difficult to evaluate the specific localization of tissue and/or cellular polyphenols, because the method is limited to chromatography. To overcome these difficulties, we have developed anti-polyphenol antibodies to characterize immunohistochemically the localization of polyphenols and their metabolites in vivo. Two novel monoclonal antibodies were raised against quercetin and tea catechins, which represent flavonoid-type polyphenols distributed in foods and beverages, and are expected to exhibit anti-oxidative and anti-inflammatory activities in vivo. Using these antibodies, we identified activated macrophages as a specific target of these flavonoids during the development of atherosclerotic lesions. This review describes recent findings on the molecular actions of flavonoids that underly their anti-atherosclerotic activity in vivo.

Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques

Directory of Open Access Journals (Sweden)

Elisabetta Zinellu

2012-01-01

Full Text Available Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS. The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% (P<0.01 in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability.

The chemokine and scavenger receptor CXCL16/SR-PSOX is expressed in human vascular smooth muscle cells and is induced by interferon γ

International Nuclear Information System (INIS)

Wagsaeter, Dick; Olofsson, Peder S.; Norgren, Lars; Stenberg, Bjoern; Sirsjoe, Allan

2004-01-01

Atherosclerosis is an inflammatory disease that is characterised by the involvement of chemokines that are important for the recruitment of leukocytes and scavenger receptors that mediate foam cell formation. Several cytokines are involved in the regulation of chemokines and scavenger receptors in atherosclerosis. CXCL16 is a chemokine and scavenger receptor and found in macrophages in human atherosclerotic lesions. Using double-labelled immunohistochemistry, we identified that smooth muscle cells in human lesions express CXCL16. We then analysed the effects of IFN-γ, TNF-α, IL-12, IL-15, IL-18, and LPS on CXCL16 expression in cultured aortic smooth muscle cells. IFN-γ was the most potent CXCL16 inducer and increased mRNA, soluble form, membrane form, and total cellular levels of CXCL16. The IFN-γ induction of CXCL16 was also associated with increased uptake of oxLDL into these cells. Taken together, smooth muscle cells express CXCL16 in atherosclerotic lesions, which may play a role in the attraction of T cells to atherosclerotic lesions and contribute to the cellular internalisation of modified LDL

Preintervention lesion remodelling affects operative mechanisms of balloon optimised directional coronary atherectomy procedures: a volumetric study with three dimensional intravascular ultrasound

Science.gov (United States)

von Birgelen, C; Mintz, G; de Vrey, E A; Serruys, P; Kimura, T; Nobuyoshi, M; Popma, J; Leon, M; Erbel, R; de Feyter, P J

2000-01-01

AIMS—To classify atherosclerotic coronary lesions on the basis of adequate or inadequate compensatory vascular enlargement, and to examine changes in lumen, plaque, and vessel volumes during balloon optimised directional coronary atherectomy procedures in relation to the state of adaptive remodelling before the intervention.
DESIGN—29 lesion segments in 29 patients were examined with intravascular ultrasound before and after successful balloon optimised directional coronary atherectomy procedures, and a validated volumetric intravascular ultrasound analysis was performed off-line to assess the atherosclerotic lesion remodelling and changes in plaque and vessel volumes that occurred during the intervention. Based on the intravascular ultrasound data, lesions were classified according to whether there was inadequate (group I) or adequate (group II) compensatory enlargement.
RESULTS—There was no significant difference in patient and lesion characteristics between groups I and II (n = 10 and 19), including lesion length and details of the intervention. Quantitative coronary angiographic data were similar for both groups. However, plaque and vessel volumes were significantly smaller in group I than in II. In group I, 9 (4)% (mean (SD)) of the plaque volume was ablated, while in group II 16 (11)% was ablated (p = 0.01). This difference was reflected in a lower lumen volume gain in group I than in group II (46 (18) mm3 v 80 (49) mm3 (p atherectomy procedures. Plaque ablation was found to be particularly low in lesions with inadequate compensatory vascular enlargement.


Keywords: intravascular ultrasound; ultrasonics; remodelling; coronary artery disease; atherectomy PMID:10648496

Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

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Fukuda, Kazuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Senokuchi, Takafumi; Ishii, Norio; Kinoshita, Hiroyuki; Yamada, Sarie; Murakami, Saiko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Nakao, Saya [Department of Environmental & Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto (Japan); Motoshima, Hiroyuki; Kondo, Tatsuya; Kukidome, Daisuke; Kawasaki, Shuji [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Kawada, Teruo [Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan)

2015-01-30

Highlights: • Statins induce PPARγ activation in vascular smooth muscle cells. • Statin-induced PPARγ activation is mediated by COX-2 expression. • Statins suppress cell migration and proliferation in vascular smooth muscle cells. • Statins inhibit LPS-induced inflammatory responses by PPARγ activation. • Fluvastatin suppress the progression of atherosclerosis and induces PPARγ activation in the aorta of apoE-deficient mice. - Abstract: The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe{sup −/−} mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe{sup −/−} mice. In conclusion, statins mediate anti-atherogenic effects

Emerging Technology Update Intravascular Photoacoustic Imaging of Vulnerable Atherosclerotic Plaque.

Science.gov (United States)

Wu, Min; Fw van der Steen, Antonius; Regar, Evelyn; van Soest, Gijs

2016-10-01

The identification of vulnerable atherosclerotic plaques in the coronary arteries is emerging as an important tool for guiding atherosclerosis diagnosis and interventions. Assessment of plaque vulnerability requires knowledge of both the structure and composition of the plaque. Intravascular photoacoustic (IVPA) imaging is able to show the morphology and composition of atherosclerotic plaque. With imminent improvements in IVPA imaging, it is becoming possible to assess human coronary artery disease in vivo . Although some challenges remain, IVPA imaging is on its way to being a powerful tool for visualising coronary atherosclerotic features that have been specifically associated with plaque vulnerability and clinical syndromes, and thus such imaging might become valuable for clinical risk assessment in the catheterisation laboratory.

Natural history of severe atheromatous disease of the thoracic aorta: a transesophageal echocardiographic study.

Science.gov (United States)

Montgomery, D H; Ververis, J J; McGorisk, G; Frohwein, S; Martin, R P; Taylor, W R

1996-01-01

This study sought to prospectively observe the morphologic and clinical natural history of severe atherosclerotic disease of the thoracic aorta as defined by transesophageal echocardiography. Atherosclerosis of the thoracic aorta has been shown to be highly associated with risk for embolic events in transesophageal studies, but the natural history of the disease under clinical conditions has not been reported. During a 20-month period, 191 of 264 patients undergoing transesophageal echocardiography had adequate visualization of the aorta to allow atherosclerotic severity to be graded as follows: grade I = normal (44 patients); grade II = intimal thickening (52 patients); grade III = atheroma or = 5 mm (19 patients); grade V = mobile lesion (14 patients). All available patients with grades IV (8 patients) and V (10 patients) disease as well as a subgroup of 12 patients with grade III disease had follow-up transesophageal echocardiographic studies (mean [+/- SD] 11.7 +/- 0.9 months, range 6 to 22). Of 30 patients undergoing follow-up transesophageal echocardiographic studies, 20 (66%) had no change in atherosclerotic severity grade. Of the remaining 10 patients, atherosclerotic severity progressed one grade in 7 and decreased in 3 with resolved mobile lesions. Of 18 patients with grade IV or V disease of the aorta who underwent a follow-up study, 11 (61%) demonstrated formation of new mobile lesions. Of 10 patients with grade V disease on initial study who underwent follow-up study, 7 (70%) demonstrated resolution of a specific previously documented mobile lesion. However, seven patients (70%) with grade V disease also demonstrated development of a new mobile lesion. Of 33 patients with grade IV or V disease, 8 (24%) died during the study period, and 1 (3%) had a clinical embolic event. The presence of severe atherosclerotic disease of the thoracic aorta as defined by transesophageal echocardiography is associated with a high mortality rate. Although the morphologic

Serial changes of coronary atherosclerotic plaque: Assessment with 64-slice multi-detector computed tomography

Energy Technology Data Exchange (ETDEWEB)

Kim, Eun Young; Kang, Doo Kyoung; Sun, Joo Sung; Choi, So Yeon [Ajou University School of Medicine, Suwon (Korea, Republic of)

2013-12-15

Evaluate the progression of coronary atherosclerotic plaque during follow-up, and its association with cardiovascular risk factors. Fifty-six atherosclerotic patients with plaque were enrolled in this retrospective study. Patient's plaque was detected on repeat 64-slice multidetector CT scans with a mean interval of 25 ± 10 months changes in calcified and non-calcified plaque volumes and cardiovascular risk factors were assessed over time. Absolute and relative changes in plaque volume were compared, and the association between rapid progression and cardiovascular risk factors was determined. Diameter of the stenosis, length, calcified and non-calcified lesion plaque volumes increased significantly on follow-up CT. Absolute and relative annual changes in plaque volumes were significantly greater in non-calcified plaque (median, 22.7 mm{sup 3}, 90.4%) than in calcified plaque (median, 0.7 mm{sup 3}, 0%). Obesity, smoking, hypertension, hypercholesterolemia, and low high-density lipoprotein were significant predictors of progression of non-calcified plaque. Progression of calcified plaque was not associated with any cardiovascular risk factors. Coronary plaque volume increased significantly on follow-up CT. The rate of progression is related to non-calcified plaque than to calcified plaque. Cardiovascular risk factors are independently associated with the rapid progression of non-calcified plaque volume, but not associated with the progression of calcified plaque.

Ultrastructural characteristics of the vascular wall components of ruptured atherosclerotic abdominal aortic aneurysm

Directory of Open Access Journals (Sweden)

Tanasković Irena

2013-01-01

Full Text Available The aim of this study was to determine the ultrastructural characteristics of cell populations and extracellular matrix components in the wall of ruptured atherosclerotic abdominal aortic aneurysm (AAA. We analyzed 20 samples of ruptured AAA. For orientation to the light microscopy, we used routine histochemical techniques by standard procedures. For ultrastructural analysis, we applied transmission electron microscopy (TEM. Our results have shown that ruptured AAA is characterized by the remains of an advanced atherosclerotic lesion in the intima followed by a complete absence of endothelial cells, the disruption of basal membrane and disruption of internal elastic lamina. On plaque margins as well as in the inner media we observed smooth muscle cells (SMCs that posses a euchromatic nucleus, a well-developed granulated endoplasmic reticulum around the nucleus and reduced myofilaments. The remains of the ruptured lipid core were acellular in all samples; however, on the lateral sides of ruptured plaque we observed a presence of two types of foam cells (FCs, spindle- and star-shaped. Fusiform FCs possess a well-differentiated basal lamina, caveolae and electron dense bodies, followed by a small number of lipid droplets in the cytoplasm. Star-shaped FCs contain a large number of lipid droplets and do not possess basal lamina. On the inner margins of the plaque, we observed a large number of cells undergoing apoptosis and necrosis, extracellular lipid droplets as well as a large number of lymphocytes. The media was thinned out with disorganized elastic lamellas, while the adventitia exhibited leukocyte infiltration. The presented results suggest that atherosclerotic plaque in ruptured AAA contains vascular SMC synthetic phenotype and two different types of FCs: some were derived from monocyte/macrophage lineage, while others were derived from SMCs of synthetic phenotype. The striking plaque hypocellularity was the result of apoptosis and necrosis

Uptake of inflammatory cell marker [{sup 11}C]PK11195 into mouse atherosclerotic plaques

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Laitinen, Iina; Marjamaeki, Paeivi; Naagren, Kjell; Roivainen, Anne; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Laine, V.J.O. [Turku University Hospital, Department of Pathology, Turku (Finland); Wilson, Ian [GE Healthcare Biosciences, Medical Diagnostics, London (United Kingdom); Leppaenen, Pia; Ylae-Herttuala, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland)

2009-01-15

The ligand [{sup 11}C]PK11195 binds with high affinity and selectivity to peripheral benzodiazepine receptor, expressed in high amounts in macrophages. In humans, [{sup 11}C]PK11195 has been used successfully for the in vivo imaging of inflammatory processes of brain tissue. The purpose of this study was to explore the feasibility of [{sup 11}C]PK11195 in imaging inflammation in the atherosclerotic plaques. The presence of PK11195 binding sites in the atherosclerotic plaques was verified by examining the in vitro binding of [{sup 3}H]PK11195 onto mouse aortic sections. Uptake of intravenously administered [{sup 11}C]PK11195 was studied ex vivo in excised tissue samples and aortic sections of a LDLR/ApoB48 atherosclerotic mice. Accumulation of the tracer was compared between the atherosclerotic plaques and non-atherosclerotic arterial sites by autoradiography and histological analyses. The [{sup 3}H]PK11195 was found to bind to both the atherosclerotic plaques and the healthy wall. The autoradiography analysis revealed that the uptake of [{sup 11}C]PK11195 to inflamed regions in plaques was more prominent (p = 0.011) than to non-inflamed plaque regions, but overall it was not higher than the uptake to the healthy vessel wall. Also, the accumulation of {sup 11}C radioactivity into the aorta of the atherosclerotic mice was not increased compared to the healthy control mice. Our results indicate that the uptake of [{sup 11}C]PK11195 is higher in inflamed atherosclerotic plaques containing a large number of inflammatory cells than in the non-inflamed plaques. However, the tracer uptake to other structures of the artery wall was also prominent and may limit the use of [{sup 11}C]PK11195 in clinical imaging of atherosclerotic plaques. (orig.)

International Conference: Paraoxonases - Basic and Clinical Directions of Current Research (1st) Held in Ann Arbor, Michigan on April 22-24, 2004

National Research Council Canada - National Science Library

Weber, Wendell W

2005-01-01

.... PON 1 hydrolyzed cholesteryl linoleate hydroperoxides (CL-OOH) in oxidized LDL, HDL and macrophages and in human and mice atherosclerotic coronary or carotid lesions, yielding in the formation of linoleic acid hydroperoxides (L-OOH...

An assessment on the incremental value of high-resolution magnetic resonance imaging to identify culprit plaques in atherosclerotic disease of the middle cerebral artery

International Nuclear Information System (INIS)

Teng, Zhongzhao; Graves, Martin J.; Gillard, Jonathan H.; Peng, Wenjia; Zhan, Qian; Zhang, Xuefeng; Liu, Qi; Chen, Shiyue; Tian, Xia; Chen, Luguang; Lu, Jianping; Brown, Adam J.

2016-01-01

Although certain morphological features depicted by high resolution, multi-contrast magnetic resonance imaging (hrMRI) have been shown to be different between culprit and non-culprit middle cerebral artery (MCA) atherosclerotic lesions, the incremental value of hrMRI to define culprit lesions over stenosis has not been assessed. Patients suspected with MCA stenosis underwent hrMRI. Lumen and outer wall were segmented to calculate stenosis, plaque burden (PB), volume (PV), length (PL) and minimum luminal area (MLA). Data from 165 lesions (112 culprit and 53 non-culprit) in 139 individuals were included. Culprit lesions were larger and longer with a narrower lumen and increased PB compared with non-culprit lesions. More culprit lesions showed contrast enhancement. Both PB and MLA were better indicators than stenosis in differentiating lesion types (AUC were 0.649, 0.732 and 0.737 for stenosis, PB and MLA, respectively). Combinations of PB, MLA and stenosis could improve positive predictive value (PPV) and specificity significantly. An optimal combination of stenosis ≥ 50 %, PB ≥ 77 % and MLA ≤ 2.0 mm 2 produced a PPV = 85.7 %, negative predictive value = 54.1 %, sensitivity = 69.6 %, specificity = 75.5 %, and accuracy = 71.5 %. hrMRI plaque imaging provides incremental information to luminal stenosis in identifying culprit lesions. (orig.)

HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation.

Science.gov (United States)

Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Cholez, Guy; Ackermann, Rose; Sy, Gavin; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

2015-01-01

CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse "flow cessation model," in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively. These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that high doses of HDL and CER-001 induce a rapid and

Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs.

Science.gov (United States)

Jacobsen, Kevin; Lund, Marie Bek; Shim, Jeong; Gunnersen, Stine; Füchtbauer, Ernst-Martin; Kjolby, Mads; Carramolino, Laura; Bentzon, Jacob Fog

2017-10-05

Fibrous cap smooth muscle cells (SMCs) protect atherosclerotic lesions from rupturing and causing thrombosis, while other plaque SMCs may have detrimental roles in plaque development. To gain insight into recruitment of different plaque SMCs, we mapped their clonal architecture in aggregation chimeras of eGFP+Apoe-/- and Apoe-/- mouse embryos and in mice with a mosaic expression of fluorescent proteins in medial SMCs that were rendered atherosclerotic by PCSK9-induced hypercholesterolemia. Fibrous caps in aggregation chimeras were found constructed from large, endothelial-aligned layers of either eGFP+ or nonfluorescent SMCs, indicating substantial clonal expansion of a few cells. Similarly, plaques in mice with SMC-restricted Confetti expression showed oligoclonal SMC populations with little intermixing between the progeny of different medial SMCs. Phenotypes comprised both ACTA2+ SMCs in the cap and heterogeneous ACTA2- SMCs in the plaque interior, including chondrocyte-like cells and cells with intracellular lipid and crystalline material. Fibrous cap SMCs were invariably arranged in endothelium-aligned clonal sheets, confirming results in the aggregation chimeras. Analysis of the clonal structure showed that a low number of local medial SMCs partake in atherosclerosis and that single medial SMCs can produce several different SMC phenotypes in plaque. The combined results show that few medial SMCs proliferate to form the entire phenotypically heterogeneous plaque SMC population in murine atherosclerosis.

Treatment of intracranial atherosclerotic stenoses with balloon dilatation and self-expanding stent deployment (WingSpan)

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Henkes, H. [Robert Janker Klinik, Bonn (Germany); Alfried Krupp Krankenhaus, Klinik fuer Radiologie und Neuroradiologie, Essen (Germany); Miloslavski, E.; Lowens, S.; Reinartz, J. [Robert Janker Klinik, Bonn (Germany); Liebig, T.; Kuehne, D. [Alfried Krupp Krankenhaus, Klinik fuer Radiologie und Neuroradiologie, Essen (Germany)

2005-03-01

The endovascular treatment of atherosclerotic intracranial arterial stenoses has previously been based on balloon dilatation or the deployment of a balloon expandable stent. Both methods have advantages (balloon: flexibility; balloon expandable stent: high radial force) and drawbacks (balloon: risk of elastic recoil and dissection; balloon expandable stent: limited flexibility, risk of injury to the vessel due to excessive straightening, overexpansion at ends of stent). A new combination of balloon dilatation, followed by the deployment of a self-expanding microstent has been applied in 15 patients with atherosclerotic arterial stenoses, symptomatic despite medical treatment. An anatomically and clinically adequate result was achieved in all patients. The initial degree of stenosis was 72% (mean). Balloon dilatation resulted in an average residual stenosis of 54% (mean), reduced further to a mean of 38% after stent deployment. Arterial dissection, occlusion of the target artery or symptomatic distal emboli was not encountered. In one patient, a side branch occlusion occurred after dilatation of a M1 stenosis, with complete neurological recovery. All patients were either stable or improved 4 weeks after the treatment. Recurrent TIA did not occur in any patient. Balloon dilatation and subsequent deployment of a self-expandable stent for the treatment of symptomatic intracranial arterial stenoses combines the advantages of both techniques and allows a rapid, clinically effective and technically safe treatment of these frequently challenging lesions. (orig.)

Treatment of intracranial atherosclerotic stenoses with balloon dilatation and self-expanding stent deployment (WingSpan)

International Nuclear Information System (INIS)

Henkes, H.; Miloslavski, E.; Lowens, S.; Reinartz, J.; Liebig, T.; Kuehne, D.

2005-01-01

The endovascular treatment of atherosclerotic intracranial arterial stenoses has previously been based on balloon dilatation or the deployment of a balloon expandable stent. Both methods have advantages (balloon: flexibility; balloon expandable stent: high radial force) and drawbacks (balloon: risk of elastic recoil and dissection; balloon expandable stent: limited flexibility, risk of injury to the vessel due to excessive straightening, overexpansion at ends of stent). A new combination of balloon dilatation, followed by the deployment of a self-expanding microstent has been applied in 15 patients with atherosclerotic arterial stenoses, symptomatic despite medical treatment. An anatomically and clinically adequate result was achieved in all patients. The initial degree of stenosis was 72% (mean). Balloon dilatation resulted in an average residual stenosis of 54% (mean), reduced further to a mean of 38% after stent deployment. Arterial dissection, occlusion of the target artery or symptomatic distal emboli was not encountered. In one patient, a side branch occlusion occurred after dilatation of a M1 stenosis, with complete neurological recovery. All patients were either stable or improved 4 weeks after the treatment. Recurrent TIA did not occur in any patient. Balloon dilatation and subsequent deployment of a self-expandable stent for the treatment of symptomatic intracranial arterial stenoses combines the advantages of both techniques and allows a rapid, clinically effective and technically safe treatment of these frequently challenging lesions. (orig.)

Bilirubin and atherosclerotic diseases.

Science.gov (United States)

Vítek, L

2017-04-05

Bilirubin is the final product of heme catabolism in the systemic circulation. For decades, increased serum/plasma bilirubin levels were considered an ominous sign of an underlying liver disease. However, data from recent years convincingly suggest that mildly elevated bilirubin concentrations are associated with protection against various oxidative stress-mediated diseases, atherosclerotic conditions being the most clinically relevant. Although scarce data on beneficial effects of bilirubin had been published also in the past, it took until 1994 when the first clinical study demonstrated an increased risk of coronary heart disease in subjects with low serum bilirubin levels, and bilirubin was found to be a risk factor for atherosclerotic diseases independent of standard risk factors. Consistent with these results, we proved in our own studies, that subjects with mild elevation of serum levels of unconjugated bilirubin (benign hyperbilirubinemia, Gilbert syndrome) have much lower prevalence/incidence of coronary heart as well as peripheral vascular disease. We have also demonstrated that this association is even more general, with serum bilirubin being a biomarker of numerous other diseases, often associated with increased risk of atherosclerosis. In addition, very recent data have demonstrated biological pathways modulated by bilirubin, which are responsible for observed strong clinical associations.

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease

DEFF Research Database (Denmark)

Hansen, Peter Riis

2018-01-01

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory...... pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future...... prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations...

Theoretical approach of complex DNA lesions: from formation to repair

International Nuclear Information System (INIS)

Bignon, Emmanuelle

2017-01-01

This thesis work is focused on the theoretical modelling of DNA damages, from formation to repair. Several projects have been led in this framework, which can be sorted into three different parts. One on hand, we studied complex DNA reactivity. It included a study about 8-oxo-7,8-dihydro-guanine (8oxoG) mechanisms of formation, a project concerning the UV-induced pyrimidine 6-4 pyrimidone (6-4PP) endogenous photo-sensitizer features, and another one about DNA photo-sensitization by nonsteroidal anti-inflammatory drugs (i.e. ketoprofen and ibuprofen). On the other hand, we investigated mechanical properties of damaged DNA. The structural signature of a DNA lesion is of major importance for their repair, unfortunately only few NMR and X-ray structures of such systems are available. In order to gain insights into their dynamical structure, we investigated a series of complex damages: clustered abasic sites, interstrand cross-links, and the 6-4PP photo-lesion. Likewise, we studied the interaction modes DNA with several polyamines, which are well known to interact with the double helix, but also with the perspective to model DNA-protein cross-linking. The third part concerned the study of DNA interactions with repair enzymes. In line with the structural study about clustered abasic sites, we investigated the dynamics of the same system, but this time interacting with the APE1 endonuclease. We also studied interactions between the Fpg glycosylase with an oligonucleotides containing tandem 8-oxoG on one hand and 8-oxoG - abasic site as multiply damaged sites. Thus, we shed new lights on damaged DNA reactivity, structure and repair, which provides perspectives for biomedicine and life's mechanisms understanding as we begin to describe nucleosomal DNA. (author)

Extra-Virgin Olive Oil with Natural Phenolic Content Exerts an Anti-Inflammatory Effect in Adipose Tissue and Attenuates the Severity of Atherosclerotic Lesions in Ldlr-/-.Leiden Mice.

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Luque-Sierra, Amparo; Alvarez-Amor, Leticia; Kleemann, Robert; Martín, Franz; Varela, Lourdes M

2018-05-15

The present study investigates the effect of olive oils with different phenolic content in high-fat diets (HFDs) on hypertrophy and inflammation in adipose tissue and associated atherosclerosis, in the context of obesity. Ldlr-/-.Leiden mice were fed three different HFDs for 32 weeks and were compared with mice fed the standard low-fat diet (LFD). The different fats provided in the HFDs were lard (HFD-L), extra-virgin olive oil (EVOO; 79 mg kg -1 of phenolic compounds, HFD-EVOO), or EVOO rich in phenolic compounds (OL, 444 mg kg -1 of phenolic compounds, HFD-OL). All HFD-fed mice became obese, but only HFD-L-induced adipocyte hypertrophy. HFD-EVOO mice exhibited the greatest levels of Adiponectin in adipose tissue and presented atherosclerotic lesions similar to the LFD group, with a very low count of monocyte/macrophage compared with HFD-L and HFD-OL mice. Enrichment of the phenolic content of olive oil reduced the secretion of nitrites/nitrates in the aorta, but atherosclerosis was not attenuated in HFD-OL mice compared to other HFD mice. Consumption of olive oil with a natural content of phenolic compounds attenuates adipose tissue hypertrophy and inflammation and exerts antiatherosclerotic effects in mice. A higher phenolic content of olive oil did not provide further benefits in the prevention of atherosclerosis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-atherosclerotic plants which modulate the phenotype of vascular smooth muscle cells.

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Saleh Al-Shehabi, Tuqa; Iratni, Rabah; Eid, Ali H

2016-10-15

Cardiovascular disease (CVD) remains the leading cause of global death, with atherosclerosis being a major contributor to this mortality. Several mechanisms are implicated in the pathogenesis of this disease. A key element in the development and progression of atherosclerotic lesions is the phenotype of vascular smooth muscle cells. Under pathophysiologic conditions such as injury, these cells switch from a contractile to a synthetic phenotype that often possesses high proliferative and migratory capacities. Despite major advances made in the management and treatment of atherosclerosis, mortality associated with this disease remains high. This mandates that other approaches be sought. Herbal medicine, especially for the treatment of CVD, has been gaining more attention in recent years. This is in no small part due to the evidence-based values associated with the consumption of many plants as well as the relatively cheaper prices, easier access and conventional folk medicine "inherited" over generations. Sections: In this review, we provide a brief introduction about the pathogenesis of atherosclerosis then we highlight the role of vascular smooth muscle cells in this disease, especially when a phenotypic switch of these cells arises. We then thoroughly discuss the various plants that show potentially beneficial effects as anti-atherosclerotic, with prime attention given to herbs and plants that inhibit the phenotypic switch of vascular smooth muscle cells. Accumulating evidence provides the justification for the use of botanicals in the treatment or prevention of atherosclerosis. However, further studies, especially clinical ones, are warranted to better define several pharmacological parameters of these herbs, such as toxicity, tolerability, and efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association between abdominal fat distribution and atherosclerotic changes in the carotid artery.

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Oike, Miki; Yokokawa, Hirohide; Fukuda, Hiroshi; Haniu, Tomomi; Oka, Fukuko; Hisaoka, Teruhiko; Isonuma, Hiroshi

2014-01-01

We aimed to evaluate the association between abdominal fat distribution (e.g., abdominal visceral fat area [VFA], subcutaneous fat area [SFA], and total fat area [TFA]), waist circumference (WC), or body mass index (BMI) and atherosclerotic changes in the carotid artery after adjusting for common risk factors. The present study is a hospital-based, cross-sectional study. Study participants included 223 Japanese individuals who underwent a medical health checkup at Juntendo University Hospital, Tokyo, between December 2005 and August 2011. Multivariate logistic regression analysis was used to examine the association between abdominal VFA, SFA, TFA, the VFA/SFA ratio, WC, or BMI and intima-media thickness [IMT] (mean IMT≥1.1mm or maximum IMT≥1.2mm) as atherosclerotic changes in the carotid artery. Multivariate logistic regression analysis showed that VFA (OR for ≥150cm(2) versus <100cm(2), 3.88; 95% CI, 1.39-10.85), BMI (OR for ≥27.6kg/m(2) versus <25kg/m(2), 5.22; 95% CI, 1.69-16.16), and TFA (OR for 200-285cm(2) versus <200cm(2), 4.15; 95% CI, 1.34-12.86: OR for ≥285cm(2) versus <200cm(2), 5.53; 95% CI, 1.76-17.35) were significantly associated with atherosclerotic changes in men. After adjustment for BMI, only TFA (OR for ≥285cm(2) versus <200cm(2), 3.76; 95%CI, 1.03-13.79) in men was significantly associated with atherosclerotic changes in the carotid artery. Our results indicate that VFA, TFA, and BMI are independently associated with atherosclerotic changes in Japanese men. TFA may be considered as a valuable measure of atherosclerotic changes. Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

The association of lesion eccentricity with plaque morphology and components in the superficial femoral artery: a high-spatial-resolution, multi-contrast weighted CMR study

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Zhao Xihai

2010-07-01

Full Text Available Abstract Background Atherosclerotic plaque morphology and components are predictors of subsequent cardiovascular events. However, associations of plaque eccentricity with plaque morphology and plaque composition are unclear. This study investigated associations of plaque eccentricity with plaque components and morphology in the proximal superficial femoral artery using cardiovascular magnetic resonance (CMR. Methods Twenty-eight subjects with an ankle-brachial index less than 1.00 were examined with 1.5T high-spatial-resolution, multi-contrast weighted CMR. One hundred and eighty diseased locations of the proximal superficial femoral artery (about 40 mm were analyzed. The eccentric lesion was defined as [(Maximum wall thickness- Minimum wall thickness/Maximum wall thickness] ≥ 0.5. The arterial morphology and plaque components were measured using semi-automatic image analysis software. Results One hundred and fifteen locations were identified as eccentric lesions and sixty-five as concentric lesions. The eccentric lesions had larger wall but similar lumen areas, larger mean and maximum wall thicknesses, and more calcification and lipid rich necrotic core, compared to concentric lesions. For lesions with the same lumen area, the degree of eccentricity was associated with an increased wall area. Eccentricity (dichotomous as eccentric or concentric was independently correlated with the prevalence of calcification (odds ratio 3.78, 95% CI 1.47-9.70 after adjustment for atherosclerotic risk factors and wall area. Conclusions Plaque eccentricity is associated with preserved lumen size and advanced plaque features such as larger plaque burden, more lipid content, and increased calcification in the superficial femoral artery.

Increased synthesis of heparin affin regulatory peptide in the perforant path lesioned mouse hippocampal formation

DEFF Research Database (Denmark)

Poulsen, F R; Lagord, C; Courty, J

2000-01-01

differentiation in vivo. Here we have investigated the expression of HARP mRNA and protein in the perforant path lesioned C57B1/6 mouse hippocampal formation from 1 to 35 days after surgery. This type of lesion induces a dense anterograde and terminal axonal degeneration, activation of glial cells, and reactive...... axonal sprouting within the perforant path zones of the fascia dentata and hippocampus as well as axotomy-induced retrograde neuronal degeneration in the entorhinal cortex. Analysis of sham- and unoperated control mice showed that HARP mRNA is expressed in neurons and white and gray matter glial cells...... as well as vascular and pial cells throughout the normal, adult brain. Lesioning induced high levels of HARP mRNA in astroglial-like cells in the denervated zones of fascia dentata and hippocampus as soon as day 2 postlesion. This expression reached maximum at day 4, and declined toward normal at day 7...

Exclusion of Atherosclerotic Plaque from the Circulation Using Stent-Grafts: Alternative to Carotid Stenting with a Protection Device?

International Nuclear Information System (INIS)

Peynircioglu, Bora; Geyik, Serdar; Yavuz, Kivilcim; Cil, Barbaros E.; Saatci, Isil; Cekirge, Saruhan

2007-01-01

Purpose. To retrospectively assess the feasibility, safety, and clinical mid-term outcome of patients undergoing carotid artery stenting with stent-grafts. Methods. Over a 4 year period stent-grafts were used in the endovascular treatment of symptomatic internal carotid artery stenosis in 12 patients (2 women, 10 men, aged 47-83 (mean 64) years). Protection devices were not used. Possible microembolic complications were evaluated by magnetic resonance imaging (MRI) examinations of the brain before and the day after the procedure in all patients. Mean follow-up was 22 months (range 1-42 months), by Doppler ultrasonography and conventional angiography as well as clinical examination .Results. The technical success rate was 100%. A total of 13 coronary stent-grafts were used. The mean stenosis rate (in terms of diameter) was 85% and the mean length of stent-grafts used was 20.9 mm. The mean diameter to which the stent-grafts were dilated was 4.66 mm. In-hospital complications occurred in 1 patient who suffered a minor femoral access hematoma that did not require transfusion or surgical decompression. Post-stenting diffusion-weighted MRI revealed several ipsilateral silent microemboli in only 1 case, which was completely asymptomatic. Two patients had a major stroke after 2 years of follow-up. Restenosis was found in 2 patients who underwent successful balloon dilatation followed by placement of a self-expandable bare stent within the stent-grafts. Conclusions. Stent-grafts may prevent microembolic complications during stenting of atherosclerotic carotid lesions in selected cases, offering immediate exclusion of the atherosclerotic lesion from the circulation by pressing the plaque against the vessel wall. Comparative, randomized studies in larger series of patients are needed with carotid-dedicated stent-graft designs

Association between pregnancy losses in women and risk of atherosclerotic disease in their relatives

DEFF Research Database (Denmark)

Ranthe, Mattis Flyvholm; Diaz, Lars Jorge; Behrens, Ida

2016-01-01

) and the atherosclerotic endpoint (brothers). Parents whose daughters had stillbirths had 1.14 (95% CI 1.05-1.24) and 1.07 (95% CI 0.96-1.18) times the rates of MI and CVI, respectively, as parents whose daughters had no stillbirths. CONCLUSION: Certain pregnancy losses and atherosclerotic diseases in both heart and brain......AIMS: A common underlying mechanism with a genetic component could link pregnancy losses with vascular disease. We examined whether pregnancy losses (miscarriages and stillbirths) and atherosclerotic outcomes co-aggregated in families. METHODS AND RESULTS: Using Danish registers, we identified...... women with pregnancies in 1977-2008, and their parents (>1 million) and brothers (>435 000). We followed parents for incident ischaemic heart disease (IHD), myocardial infarction (MI), and cerebrovascular infarction (CVI), and brothers for a broader combined atherosclerotic endpoint. Using Cox...

Energy deposition and the formation of biologically significant lesions by accelerated ions

International Nuclear Information System (INIS)

Kiefer, J.

1985-01-01

The assumption that the number of biologically significant lesions depends only on the amount of of energy absorbed in a critical cellular site is not able to explain the increase of RBE with LET and leads to large discrepancies between predicted and measured inactivation cross sections in the LET range between 20 and 200 keV.μm -1 . It has, therefore, to be concluded that not only the amount of energy absorbed but also the spatial pattern of this deposition plays a decisive role. In the model presented it is postulated that two or more energy deposition events in nanometre sites are required for the formation of biologically significant lesions. This cooperative action has to take place in very short times so that only interactions within a single particle track contribute. The mathematical treatment will be outlined and qualitatively shown that the model is able to predict RBE-LET relationships. The calculations use a track structure model based on classical collision mechanics. It is compared with existing experimental results showing good agreement at least for higher particle energies. (author)

Circumferential lesion formation around the pulmonary veins in the left atrium with focused ultrasound using a 2D-array endoesophageal device: a numerical study

Energy Technology Data Exchange (ETDEWEB)

Pichardo, Samuel; Hynynen, Kullervo [Imaging Research-Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room C713, Toronto, ON M4N 3M5 (Canada)

2007-08-21

Atrial fibrillation (AF) is the most frequently sustained cardiac arrhythmia affecting humans. The electrical isolation by ablation of the pulmonary veins (PVs) in the left atrium (LA) of the heart has been proven as an effective cure of AF. The ablation consists mainly in the formation of a localized circumferential thermal coagulation of the cardiac tissue surrounding the PVs. In the present numerical study, the feasibility of producing the required circumferential lesion with an endoesophageal ultrasound probe is investigated. The probe operates at 1 MHz and consists of a 2D array with enough elements (114 x 20) to steer the acoustic field electronically in a volume comparable to the LA. Realistic anatomical conditions of the thorax were considered from the segmentation of histological images of the thorax. The cardiac muscle and the blood-filled cavities in the heart were identified and considered in the sound propagation and thermal models. The influence of different conditions of the thermal sinking in the LA chamber was also studied. The circumferential ablation of the PVs was achieved by the sum of individual lesions induced with the proposed device. Different scenarios of lesion formation were considered where ultrasound exposures (1, 2, 5 and 10 s) were combined with maximal peak temperatures (60, 70 and 80 {sup 0}C). The results of this numerical study allowed identifying the limits and best conditions for controlled lesion formation in the LA using the proposed device. A controlled situation for the lesion formation surrounding the PVs was obtained when the targets were located within a distance from the device in the range of 26 {+-} 7 mm. When combined with a maximal temperature of 70 {sup 0}C and an exposure time between 5 and 10 s, this distance ensured preservation of the esophageal structures, controlled lesion formation and delivery of an acoustic intensity at the transducer surface that is compatible with existing materials. With a peak

68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

International Nuclear Information System (INIS)

Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani; Iveson, Peter; Wilson, Ian; Karlsen, Hege; Cuthbertson, Alan; Laine, Jukka; Leppaenen, Pia; Ylae-Herttula, Seppo; Roivainen, Anne

2009-01-01

Increased expression of αvβ3/αvβ5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel 68 Ga-DOTA-RGD peptide binds with high affinity to αvβ3/αvβ5 integrin. The aim of this study was to investigate the uptake of the 68 Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered 68 Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR -/- ApoB 100/100 atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced 68 Ga. The tracer had reasonably good specific radioactivity (8.7 ± 1.1 GBq/μmol) and was quite stable in vivo. According to ex vivo biodistribution results, 68 Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of 68 Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio ± SD 1.4 ± 0.1, p = 0.0004). We observed that 68 Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

Mathematical modeling of atherosclerotic plaque destabilization: Role of neovascularization and intraplaque hemorrhage.

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Guo, Muyi; Cai, Yan; Yao, Xinke; Li, Zhiyong

2018-08-07

Observational studies have identified angiogenesis from the adventitial vasa vasorum and intraplaque hemorrhage (IPH) as critical factors in atherosclerotic plaque progression and destabilization. Here we propose a mathematical model incorporating intraplaque neovascularization and hemodynamic calculation with plaque destabilization for the quantitative evaluation of the role of neoangiogenesis and IPH in the vulnerable atherosclerotic plaque formation. An angiogenic microvasculature is generated by two-dimensional nine-point discretization of endothelial cell proliferation and migration from the vasa vasorum. Three key cells (endothelial cells, smooth muscle cells and macrophages) and three key chemicals (vascular endothelial growth factors, extracellular matrix and matrix metalloproteinase) are involved in the plaque progression model, and described by the reaction-diffusion partial differential equations. The hemodynamic calculation of the microcirculation on the generated microvessel network is carried out by coupling the intravascular, interstitial and transvascular flow. The plasma concentration in the interstitial domain is defined as the description of IPH area according to the diffusion and convection with the interstitial fluid flow, as well as the extravascular movement across the leaky vessel wall. The simulation results demonstrate a series of pathophysiological phenomena during the vulnerable progression of an atherosclerotic plaque, including the expanding necrotic core, the exacerbated inflammation, the high microvessel density (MVD) region at the shoulder areas, the transvascular flow through the capillary wall and the IPH. The important role of IPH in the plaque destabilization is evidenced by simulations with varied model parameters. It is found that the IPH can significantly speed up the plaque vulnerability by increasing necrotic core and thinning fibrous cap. In addition, the decreased MVD and vessel permeability may slow down the process of

Cigarette smoking and cardio-renal events in patients with atherosclerotic renal artery stenosis.

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Christopher A Drummond

Full Text Available Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731 clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931 were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001. In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD. Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001. Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01 whereas creatinine and estimated glomerular filtration rate (eGFR were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.

Application of the Enterprise Stent in Atherosclerotic Intracranial Arterial Stenosis: A Series of 60 Cases.

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Wang, Xiaofei; Wang, Zhigang; Wang, Chengwei; Ji, Yong; Ding, Xuan; Zang, Yizheng

2016-01-01

We assessed the safety and effectiveness of the Enterprise stent in treating atherosclerotic intracranial arterial stenosis (AIAS). This was a retrospective study conducted with 60 consecutive patients with 62 AIAS lesions who received the Enterprise stent at the Department of Neurosurgery, Second Hospital of Shandong University between June 2012 and January 2014. All patients were assessed using the modified Rankin scoring system at discharge. Clinical follow-ups and digital subtraction angiography (DSA) were performed at 1, 3, 6 and 12 months postoperatively. There were 42 men and 18 women with a mean age of 56.8 ± 8.0 years. Fourteen lesions (22.6%) were at the anterior and 48 (77.4 %) were at the posterior circulation. The mean stenosis rate was 76.3 ± 12.7%. The mean stenotic vessel length was 7.7 ± 2.0 mm. The technical success rate was 100%. The mean post-stent residual stenosis rate was 22.8 ± 4.8%. Five patients (8.3%) had perioperative complications, but no disability or mortality occurred within 30 days. The mean follow-up duration was 6.2 months. DSA was used to evaluate 45 lesions (72.6%) six months postoperatively: 6 (13.3%) had postoperative restenoses, 2 at the anterior circulation, and 4 at the posterior circulation. Of these 6, 4 (66.7%) were immediate residual stenoses after stenting. The residual stenosis rate was identified as a risk factor for restenosis. Five (8.3%) ischemic events, consistent with the vascular lesions, occurred. Application of the Enterprise stent was safe and efficacious. The technical success rate was high while the perioperative complication rate was low.

Amputation of extremity in patients with atherosclerotic gangrene

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Tsareva Yu.O.

2011-12-01

Full Text Available Aim of investigation — to analyze the results of treatment of patients with atherosclerotic gangrene of a limb, to identify the causes of adverse outcomes amputation. Materials and methods: We analyzed the results of examination and treatment of 218 patients with atherosclerotic gangrene of the limb. Good outcome of amputation was considered the primary surgical wound healing of the stump. Suppuration, secondary healing, re-amputation and death we attributed to the adverse results of amputation. Results: The adverse outcomes of amputation due to technical errors in surgery, properly chosen level, inadequate drainage of the wound stump, an unsuccessful operation on the arteries of a limb, inadequate empirical antibiotic therapy, patient's age, functional capabilities of myocardium, the duration of critical ischemia, as well as the lack of psychological adaptation of patients before amputation. Conclusion: To decide the need for amputation in patients with atherosclerotic gangrene follows the assessment of possible vascular reconstructive surgery. In determining the level of amputation is necessary to objectively assess the degree of disruption of regional blood flow using multilevel manometry and laser Dopplerflowmetry. In preparation for amputation should be paid special attention to the correction of rheological and coagulation properties of blood, normalization of the functional state of the myocardium, as well as specialized psychotherapeutic training for timely and adequate psychological adaptation of the patient

Correlation between local hemodynamics and lesion distribution in a novel aortic regurgitation murine model of atherosclerosis.

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Hoi, Yiemeng; Zhou, Yu-Qing; Zhang, Xiaoli; Henkelman, R Mark; Steinman, David A

2011-05-01

Following surgical induction of aortic valve regurgitation (AR), extensive atherosclerotic plaque development along the descending thoracic and abdominal aorta of Ldlr⁻/⁻ mice has been reported, with distinct spatial distributions suggestive of a strong local hemodynamic influence. The objective of this study was to test, using image-based computational fluid dynamics (CFD), whether this is indeed the case. The lumen geometry was reconstructed from micro-CT scanning of a control Ldlr⁻/⁻ mouse, and CFD simulations were carried out for both AR and control flow conditions derived from Doppler ultrasound measurements and literature data. Maps of time-averaged wall shear stress magnitude (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT) were compared against the spatial distributions of plaque stained with oil red O, previously acquired in a group of AR and control mice. Maps of OSI and RRT were found to be consistent with plaque distributions in the AR mice and the absence of plaque in the control mice. TAWSS was uniformly lower under control vs. AR flow conditions, suggesting that levels (> 100 dyn/cm²) exceeded those required to alone induce a pro-atherogenic response. Simulations of a straightened CFD model confirmed the importance of anatomical curvature for explaining the spatial distribution of lesions in the AR mice. In summary, oscillatory and retrograde flow induced in the AR mice, without concomitant low shear, may exacerbate or accelerate lesion formation, but the distinct anatomical curvature of the mouse aorta is responsible for the spatial distribution of lesions.

Peripheral ARtery Atherosclerotic DIsease and SlEep disordered breathing (PARADISE) trial - protocol for an observational cohort study.

Science.gov (United States)

Szymański, Filip M; Gałązka, Zbigniew; Płatek, Anna E; Górko, Dariusz; Ostrowski, Tomasz; Adamkiewicz, Karolina; Łęgosz, Paweł; Ryś, Anna; Semczuk-Kaczmarek, Karolina; Celejewski, Krzysztof; Filipiak, Krzysztof J

2017-01-01

increased oxidative stress and vascular endothelial injury associated with OSA, patients afflicted with this condition will not only have more advanced atherosclerotic lesions, but also in their histopathological examination their atherosclerotic plaque will exhibit evidence of greater instability and adverse morphology. We also expect to show that in patients with OSA, achieving cor¬rect control of cardiovascular risk factors will be more difficult. The study may improve PAD control through assuring better multispecialty care in PAD patients.

The contemporary management of intracranial atherosclerotic disease.

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Leng, Xinyi; Wong, Ka Sing; Leung, Thomas W

2016-06-01

Intracranial atherosclerotic disease is the most common cause of cerebral vasculopathy and an important stroke etiology worldwide, with a higher prevalence in Asian, Hispanic and African ethnicities. Symptomatic intracranial atherosclerotic disease portends a recurrent stroke risk as high as 18% at one year. The key to secondary prevention is an understanding of the underlying stroke mechanism and aggressive control of conventional cardiovascular risks. Contemporary treatment includes antiplatelet therapy, optimal glycemic and blood pressure control, statin therapy and lifestyle modifications. For patients with high-grade (70-99%) symptomatic steno-occlusion, short-term dual antiplatelet therapy with aspirin and clopidogrel followed by life-long single antiplatelet therapy may reduce the recurrent risk. Current evidence does not advocate percutaneous transluminal angioplasty and stenting as an initial treatment. External counterpulsation, encephaloduroarteriosynangiosis and remote limb ischemic preconditioning are treatments under investigation. Future studies should aim at predicting patients prone to recurrence despite of medical therapies and testing the efficacy of emerging therapies.

Evaluation by multislice computed tomography of atherosclerotic coronary artery plaques in non-culprit, remote coronary arteries of patients with acute coronary syndrome

International Nuclear Information System (INIS)

Kunimasa, Taeko; Sugi, Kaoru; Moroi, Masao; Sato, Yuichi

2005-01-01

Patients with acute coronary syndrome (ACS) frequently have vulnerable plaques in the remote coronary arteries, suggesting that ACS is part of the pan-coronary process. In the present study the computed tomography (CT) plaque density in non-culprit atherosclerotic coronary artery lesions was evaluated by multi-slice computed tomography (MSCT) in patients with ACS and non-ACS. MSCT was performed in 21 patients with ACS and 53 patients with non-ACS: 16 of the 21 ACS patients (76%) and 30 of the non-ACS 53 patients (57%) had non-calcified plaques in the non-culprit coronary arteries (p=0.18). CT-low-density plaques (CT density <68 Hounsfield units (HU)) were more frequent in the ACS group (13/16 patients, 81%) than in the non-ACS group (13/30 patients, 43%, p=0.03). In addition, the CT density of the non-culprit lesion was significantly lower in patients with ACS than in those with non-ACS (44.1±22.9 and 77.3±33.7 HU, respectively). Patients with ACS more frequently had CT-low-density plaques in the non-culprit, remote arteries than those with non-ACS, which suggests that ACS treatment should focus not only on stabilizing the culprit lesion but also on systemic stabilization of non-culprit lesions. (author)

Parietal Epithelial Cells Participate in the Formation of Sclerotic Lesions in Focal Segmental Glomerulosclerosis

Science.gov (United States)

Smeets, Bart; Kuppe, Christoph; Sicking, Eva-Maria; Fuss, Astrid; Jirak, Peggy; van Kuppevelt, Toin H.; Endlich, Karlhans; Wetzels, Jack F.M.; Gröne, Hermann-Josef; Floege, Jürgen

2011-01-01

The pathogenesis of the development of sclerotic lesions in focal segmental glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes or parietal epithelial cells (PECs) to determine whether PECs contribute to sclerosis. In three distinct models of FSGS (5/6-nephrectomy + DOCA-salt; the murine transgenic chronic Thy1.1 model; or the MWF rat) and in human biopsies, the primary injury to induce FSGS associated with focal activation of PECs and the formation of cellular adhesions to the capillary tuft. From this entry site, activated PECs invaded the affected segment of the glomerular tuft and deposited extracellular matrix. Within the affected segment, podocytes were lost and mesangial sclerosis developed within the endocapillary compartment. In conclusion, these results demonstrate that PECs contribute to the development and progression of the sclerotic lesions that define FSGS, but this pathogenesis may be relevant to all etiologies of glomerulosclerosis. PMID:21719782

Tyrosine phosphorylation of platelet derived growth factor β receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris

Science.gov (United States)

Abe, J; Deguchi, J; Takuwa, Y; Hara, K; Ikari, Y; Tamura, T; Ohno, M; Kurokawa, K

1998-01-01

Background—Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase activation and subsequent cellular migration, proliferation, and vascular contraction.
Aims—To investigate whether the concentration of PDGF β receptor tyrosine phosphorylation obtained from directional coronary atherectomy (DCA) samples correlate with atherosclerotic plaque burden, the ability of diseased vessels to remodel, coronary risk factors, and clinical events.
Methods—DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF β receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF β receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables.
Results—PDGF β receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non-atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control standard, p atherectomy;  restenosis PMID:9616351

{sup 68}Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

Energy Technology Data Exchange (ETDEWEB)

Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Iveson, Peter; Wilson, Ian [Medical Diagnostics, GE Healthcare Biosciences, London (United Kingdom); Karlsen, Hege; Cuthbertson, Alan [GE Healthcare MDx Research, Oslo (Norway); Laine, Jukka [Turku University Hospital, Department of Pathology, Turku (Finland); Leppaenen, Pia; Ylae-Herttula, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland); Roivainen, Anne [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Turku Centre for Disease Modelling, Turku (Finland)

2009-12-15

Increased expression of {alpha}v{beta}3/{alpha}v{beta}5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel {sup 68}Ga-DOTA-RGD peptide binds with high affinity to {alpha}v{beta}3/{alpha}v{beta}5 integrin. The aim of this study was to investigate the uptake of the {sup 68}Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered {sup 68}Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR{sup -/-}ApoB{sup 100/100} atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced {sup 68}Ga. The tracer had reasonably good specific radioactivity (8.7 {+-} 1.1 GBq/{mu}mol) and was quite stable in vivo. According to ex vivo biodistribution results, {sup 68}Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of {sup 68}Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio {+-} SD 1.4 {+-} 0.1, p = 0.0004). We observed that {sup 68}Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

Lipid lowering and anti-atherosclerotic properties of Tinospora ...

African Journals Online (AJOL)

atherosclerotic properties of Tinospora crispa aqueous extract (TCAE) on rabbits for 10 weeks. The hyperlipidemic rabbits were induced and the rabbit were given different concentration of TCAE (200, 450 and 600 mg/kg). Results from lipid analysis show ...

Estimating risk of atherosclerotic cardiovascular diseases in non-atherosclerotic Pakistani patients: Study conducted at National Institute of Cardiovascular Diseases, Karachi, Pakistan

International Nuclear Information System (INIS)

Ashraf, T.; Achakzai, A.S.; Farooq, F.; Memon, M.A.

2017-01-01

This cross-sectional study was carried out at the National Institute of Cardiovascular Disease, Karachi, from July 2014 to March 2015, and comprised male and female subjects with multi-ethnic background, aged 20-79 years and having non-atherosclerotic disease. SPSS 22 was used for data analysis. Results: Of the 437 participants, 174(39.8%) were men and 263(60.2%) were women. The overall mean age was 42.65+-11.45 years. The mean age of men was 43.3+-12.1 years and that of women was 42.2+-10.8 years. Moreover, ten-year and lifetime risk assessment rates were higher in men (50[28.2%] and 86[49.4%] respectively) compared to women (28[10.6%] and 84[31.9%], respectively). Conclusion: Urdu-speaking Pakistanis were found to be at higher risk from atherosclerotic cardiovascular disease.

Mechanical characterization of atherosclerotic arteries using finite-element modeling: feasibility study on mock arteries.

Science.gov (United States)

Pazos, Valérie; Mongrain, Rosaire; Tardif, Jean-Claude

2010-06-01

Clinical studies on lipid-lowering therapy have shown that changing the composition of lipid pools reduced significantly the risk of cardiac events associated with plaque rupture. It has been shown also that changing the composition of the lipid pool affects its mechanical properties. However, knowledge about the mechanical properties of human atherosclerotic lesions remains limited due to the difficulty of the experiments. This paper aims to assess the feasibility of characterizing a lipid pool embedded in the wall of a pressurized vessel using finite-element simulations and an optimization algorithm. Finite-element simulations of inflation experiments were used together with nonlinear least squares algorithm to estimate the material model parameters of the wall and of the inclusion. An optimal fit of the simulated experiment and the real experiment was sought with the parameter estimation algorithm. The method was first tested on a single-layer polyvinyl alcohol (PVA) cryogel stenotic vessel, and then, applied on a double-layered PVA cryogel stenotic vessel with a lipid inclusion.

Increased synthesis of heparin affin regulatory peptide in the perforant path lesioned mouse hippocampal formation

DEFF Research Database (Denmark)

Poulsen, F R; Lagord, C; Courty, J

2000-01-01

Heparin affin regulatory peptide (HARP), also known as pleiotrophin or heparin-binding growth-associated molecule, is a developmentally regulated extracellular matrix protein that induces cell proliferation and promotes neurite outgrowth in vitro as well as pre- and postsynaptic developmental...... differentiation in vivo. Here we have investigated the expression of HARP mRNA and protein in the perforant path lesioned C57B1/6 mouse hippocampal formation from 1 to 35 days after surgery. This type of lesion induces a dense anterograde and terminal axonal degeneration, activation of glial cells, and reactive...... axonal sprouting within the perforant path zones of the fascia dentata and hippocampus as well as axotomy-induced retrograde neuronal degeneration in the entorhinal cortex. Analysis of sham- and unoperated control mice showed that HARP mRNA is expressed in neurons and white and gray matter glial cells...

Contrast enhancement by lipid-based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study

NARCIS (Netherlands)

den Adel, Brigit; van der Graaf, Linda M.; Que, Ivo; Strijkers, Gustav J.; Löwik, Clemens W.; Poelmann, Robert E.; van der Weerd, Louise

2013-01-01

The use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of two differently sized gadolinium-based contrast agents to enhance atherosclerotic plaques in ApoE(-/-) mice was evaluated with MRI. We

Initial stress in biomechanical models of atherosclerotic plaques

NARCIS (Netherlands)

Speelman, L.; Akyildiz, A.C.; Adel, den B.; Wentzel, J.J.; Steen, van der A.F.W.; Virmani, R.; Weerd, van der L.; Jukema, J.W.; Poelmann, R.E.; Brummelen, van E.H.; Gijsen, F.J.H.

2011-01-01

Rupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the strength of the material locally. Biomechanical stress analyses are commonly based on pressurized

A framework for the co-registration of hemodynamic forces and atherosclerotic plaque components

OpenAIRE

Canton, Gador; Chiu, Bernard; Chen, Huijun; Chen, Yimin; Hatsukami, Thomas S.; Kerwin, William S.; Yuan, Chun

2013-01-01

Local hemodynamic forces, such as wall shear stress, are thought to trigger cellular and molecular mechanisms that determine atherosclerotic plaque vulnerability to rupture. Magnetic resonance imaging (MRI) has emerged as a powerful tool to characterize human carotid atherosclerotic plaque composition and morphology, and to identify plaque features shown to be key determinants of plaque vulnerability. Image-based computational fluid dynamics (CFD) has allowed researchers to obtain time-resolv...

Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation.

Science.gov (United States)

Rappl, Gunter; Pabst, Stefan; Riemann, Dagmar; Schmidt, Annette; Wickenhauser, Claudia; Schütte, Wolfgang; Hombach, Andreas A; Seliger, Barbara; Grohé, Christian; Abken, Hinrich

2011-07-01

Sarcoidosis can evolve into a chronic disease with persistent granulomas accompanied by progressive fibrosis. While an unlimited inflammatory response suggests an impaired immune control in sarcoid lesions, it stands in contrast to the massive infiltration with CD4(+)CD25(high)FoxP3(+) regulatory T cells. We here revealed that those Treg cells in affected lung lesions were mainly derived from activated natural Treg cells with GARP (LRRC32)-positive phenotype but exhibited reduced repressor capacities despite high IL-10 and TGF-beta 1 levels. The repressive capacity of blood Treg cells, in contrast, was not impaired compared to age-matched healthy donors. Treg derived cells in granuloma lesions have undergone extensive rounds of amplifications indicated by shortened telomeres compared to blood Treg cells of the same patient. Lesional Treg derived cells moreover secreted pro-inflammatory cytokines including IL-4 which sustains granuloma formation through fibroblast amplification and the activation of mast cells, the latter indicated by the expression of membrane-bound oncostatin M. Copyright © 2011 Elsevier Inc. All rights reserved.

Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques.

Directory of Open Access Journals (Sweden)

Bert Rutten

Full Text Available Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs and macrophages in human atherosclerotic carotid plaques.Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP, in two independent cohorts: the Circulating Cells cohort (n = 244 and the Athero-Express cohort (n = 91. Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort. Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort.We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range: 4153 (1585-11267 area under the curve (AUC vs. 9633 (3580-21565 AUC, P<0.001. Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean ± SD; 8969 ± 3485 AUC vs. 7020 ± 3442 AUC, P = 0.02. All associations remained significant after adjustment for age, sex and use of drugs against platelet activation.Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.

Intervention with rotational atherectomy, sharp balloon and implant of conventional Stent in ostium lesion of right coronary artery, calcified

International Nuclear Information System (INIS)

Hurtado, Edgar; Echeverria, Rene; Calderon, Luis I

2004-01-01

Atherosclerotic lesions from the right coronary artery ostium have a low incidence in the manifestation of coronary disease. The high content of smooth muscle cells in the coronary ostium is related to a low success probability of a percutaneous intervention. We present a clinical complex case of a 61 years old female with right coronary artery ostium disease to whom we performed an angioplasty with cutting balloon and rotational arterectomy with successful results

Anti-Atherosclerotic Action of Agmatine in ApoE-Knockout Mice.

Science.gov (United States)

Wiśniewska, Anna; Olszanecki, Rafał; Totoń-Żurańska, Justyna; Kuś, Katarzyna; Stachowicz, Aneta; Suski, Maciej; Gębska, Anna; Gajda, Mariusz; Jawień, Jacek; Korbut, Ryszard

2017-08-04

Atherosclerosis is an inflammatory disease in which dysfunction of mitochondria play an important role, and disorders of lipid management intensify this process. Agmatine, an endogenous polyamine formed by decarboxylation of arginine, exerts a protective effect on mitochondria and modulates fatty acid metabolism. We investigated the effect of exogenous agmatine on the development of atherosclerosis and changes in lipid profile in apolipoprotein E knockout (apoE-/-) mice. Agmatine caused an approximate 40% decrease of atherosclerotic lesions, as estimated by en face and cross-section methods with an influence on macrophage but not on smooth muscle content in the plaques. Agmatine treatment did not changed gelatinase activity within the plaque area. What is more, the action of agmatine was associated with an increase in the number of high density lipoproteins (HDL) in blood. Real-Time PCR analysis showed that agmatine modulates liver mRNA levels of many factors involved in oxidation of fatty acid and cholesterol biosynthesis. Two-dimensional electrophoresis coupled with mass spectrometry identified 27 differentially expressed mitochondrial proteins upon agmatine treatment in the liver of apoE-/- mice, mostly proteins related to metabolism and apoptosis. In conclusion, prolonged administration of agmatine inhibits atherosclerosis in apoE-/- mice; however, the exact mechanisms linking observed changes and elevations of HDL plasma require further investigation.

Prediction of radiofrequency ablation lesion formation using a novel temperature sensing technology incorporated in a force sensing catheter.

Science.gov (United States)

Rozen, Guy; Ptaszek, Leon; Zilberman, Israel; Cordaro, Kevin; Heist, E Kevin; Beeckler, Christopher; Altmann, Andres; Ying, Zhang; Liu, Zhenjiang; Ruskin, Jeremy N; Govari, Assaf; Mansour, Moussa

2017-02-01

Real-time radiofrequency (RF) ablation lesion assessment is a major unmet need in cardiac electrophysiology. The purpose of this study was to assess whether improved temperature measurement using a novel thermocoupling (TC) technology combined with information derived from impedance change, contact force (CF) sensing, and catheter orientation allows accurate real-time prediction of ablation lesion formation. RF ablation lesions were delivered in the ventricles of 15 swine using a novel externally irrigated-tip catheter containing 6 miniature TC sensors in addition to force sensing technology. Ablation duration, power, irrigation rate, impedance drop, CF, and temperature from each sensor were recorded. The catheter "orientation factor" was calculated using measurements from the different TC sensors. Information derived from all the sources was included in a mathematical model developed to predict lesion depth and validated against histologic measurements. A total of 143 ablation lesions were delivered to the left ventricle (n = 74) and right ventricle (n = 69). Mean CF applied during the ablations was 14.34 ± 3.55g, and mean impedance drop achieved during the ablations was 17.5 ± 6.41 Ω. Mean difference between predicted and measured ablation lesion depth was 0.72 ± 0.56 mm. In the majority of lesions (91.6%), the difference between estimated and measured depth was ≤1.5 mm. Accurate real-time prediction of RF lesion depth is feasible using a novel ablation catheter-based system in conjunction with a mathematical prediction model, combining elaborate temperature measurements with information derived from catheter orientation, CF sensing, impedance change, and additional ablation parameters. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Decreased expression of vitamin D receptors in neointimal lesions following coronary artery angioplasty in atherosclerotic swine.

Directory of Open Access Journals (Sweden)

Gaurav K Gupta

Full Text Available Inflammatory cytokines, such as TNF-α, play a key role in the pathogenesis of occlusive vascular diseases. Activation of vitamin D receptors (VDR elicits both growth-inhibitory and anti-inflammatory effects. Here, we investigated the expression of TNF-α and VDR in post-angioplasty coronary artery neointimal lesions of hypercholesterolemic swine and examined the effect of vitamin D deficiency on the development of coronary restenosis. We also examined the effect of calcitriol on cell proliferation and effect of TNF-α on VDR activity and expression in porcine coronary artery smooth muscle cells (PCASMCs in-vitro.Expression of VDR and TNF-α and the effect of vitamin D deficiency in post-angioplasty coronary arteries were analyzed by immunohistochemistry and histomorphometry. Cell proliferation was examined by thymidine and BrdU incorporation assays in cultured PCASMCs. Effect of TNF-α-stimulation on the activity and expression of VDR was analyzed by luciferase assay, immunoblotting and immunocytochemistry. In-vivo, morphometric analysis of the tissues revealed typical lesions with significant neointimal proliferation. Histological evaluation showed expression of smooth muscle α-actin and significantly increased expression of TNF-α in neointimal lesions. Interestingly, there was significantly decreased expression of VDR in PCASMCs of neointimal region compared to normal media. Indeed, post-balloon angioplasty restenosis was significantly higher in vitamin D-deficient hypercholesterolemic swine compared to vitamin D-sufficient group. In-vitro, calcitriol inhibited both serum- and PDGF-BB-induced proliferation in PCASMCs and TNF-α-stimulation significantly decreased the expression and activity of VDR in PCASMCs.These data suggest that significant downregulation of VDR in proliferating smooth muscle cells in neointimal lesions could be due to atherogenic cytokines, including TNF-α. Vitamin D deficiency potentiates the development of coronary

Size and spatial orientation of uterine tissue transplants on the peritoneum crucially determine the growth and cyst formation of endometriosis-like lesions in mice.

Science.gov (United States)

Körbel, Christina; Menger, Michael D; Laschke, Matthias W

2010-10-01

In many studies in rodents, intraperitoneal endometriosis-like lesions are surgically induced by syngeneic or autologous transplantation of uterine tissue samples, which are sutured to the abdominal wall. However, until now the surgical techniques have not been standardized, and we address this issue here. Uterine tissue samples were transplanted to the peritoneum of C57BL/6 mice (four study groups, n = 7 each). Using non-invasive high-resolution ultrasound imaging over a period of 4 weeks, we analyzed growth characteristics and cyst formation of the endometriosis-like lesions which developed, in relation to mode of transplantation (syngeneic versus autologous), type of tissue fixed adjacent to the peritoneum (endometrium versus perimetrium), and size of tissue transplanted (2 versus 3 mm). Immunohistochemical analysis was also performed. When the perimetrium, with underlying myometrium, was sutured next to the host peritoneum the endometriosis-like lesions which developed exhibited a higher growth rate (Pendometriosis-like lesions. Our study demonstrates that size and spatial orientation of peritoneally fixed uterine tissue samples crucially determine growth and cyst formation of endometriotic lesions in mice. These findings should improve the standardization and reliability of future studies, performed in the frequently used mouse model of surgically induced endometriosis.

Atherosclerosis and the vulnerable plaque - imaging. Part II

International Nuclear Information System (INIS)

Worthley, S.G.; Helft, G.; Zaman, A.G.; Fuster, V.; Badimon, J.J.

2000-01-01

Atherosclerotic disease and its thrombotic complications remain the leading causes of mortality and morbidity in Western society. In Australia, cardiovascular disease (CVD) is responsible for one in every 2.4 (41%) deaths and is the leading single cause of mortality. The crucial final common process for the conversion of a non-occlusive, often clinically silent, atherosclerotic lesion to a potentially fatal condition is plaque disruption. The mortality associated with atherosclerotic disease relates to the acute coronary syndromes, including acute myocardial infarction (MI), unstable angina pectoris and sudden cardiac death. There is substantial clinical, experimental and post-mortem evidence demonstrating the role played by acute thrombosis upon a disrupted atherosclerotic plaque in the onset of acute coronary syndromes. Atherosclerotic plaque composition, rather than the stenotic severity, appears to be central in determining risk of both plaque rupture and subsequent thrombogenicity. In particular, a large lipid core and a thin fibrous cap render an atherosclerotic lesion susceptible or vulnerable to these complications. We are currently limited in our ability to identify accurately patients at risk for an acute coronary event. The armamentarium of diagnostic investigations, both non-invasive and invasive, currently clinically available is only able to provide us with data related to the stenotic severity of a coronary artery. The non-invasive testing includes stress-induced (exercise or pharmacologic) ischaemic changes in electrical repolarisation, wall motion or myocardial radioactive-tracer uptake. The invasive test of coronary angiography, although the current gold standard for the detection of coronary atherosclerotic disease, provides us with no data about the composition of the atherosclerotic lesion. However, the vast majority of acute coronary events involve a non-critically stenosed atherosclerotic lesion, and thus with currently available means of

Dynamic contrast-enhanced MRI examination of atherosclerotic plaques: an animal study using rabbit model

International Nuclear Information System (INIS)

Li Mingli; Sun Jie; Chang Xiaoyan; Jin Zhengyu

2011-01-01

Objective: The enhanced patterns of atherosclerotic plaque on dynamic contrast- enhanced MRI have not been well studied. The aim of this study was to explore the patterns of plaque enhancement and their underlying mechanism by using dynamic contrast-enhanced MRI (DCE-MRI). Methods: Atherosclerotic plaques were induced in the aorta of 12 New Zealand White rabbits by a combination of endothelial denudation and high-cholesterol diet. Ten to sixteen weeks after surgery, DCE- MRI was performed with a fast spin echo T 1 weighted sequence. Thirty-five phases of images were obtained at 71-second intervals. Gd-DTPA was injected coincident with the third scan via marginal ear vein. Specimens were harvested within 12 hours after imaging for HE staining and CD31 immunohistochemical staining which was used to highlight neo-vessels. Plaque enhancement patterns were studied and compared with histological findings. Signal intensity of each plaque section was normalized to pre-contrast signal intensity of psoas muscle, after which signal intensity versus time curve was drawn. Pearson correlation coefficient was used to reveal association between histological neo-vessel count and descriptive parameters derived from signal intensity versus time curve. Results: Plaques were significantly enhanced by Gd-DTPA. Enhancement patterns could be described as 'fast-in and slow-out'. Differences in patterns of enhancement were observed between tissues, with fibrous tissue enhanced more than lipid aggregation and leukocyte foci. Peak enhancement (1.05±0.30), initial slope (0.82±0.28) and area under the curve at early phase (4.97± 1.67) derived from signal intensity-time curve had significant correlations with neo-vessel count (117.7± 93.3) (r=0.553, 0.468, 0.554 respectively, P<0.05). Conclusions: The enhanced patterns of atherosclerotic plaque by Gd-DTPA were 'fast- in and slow-out'. Neovascularization, increased endothelial permeability and extracellular matrix may be the reasons for

Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase: A Potential-Related Gene of Atherosclerosis.

Science.gov (United States)

Zhou, Mingxue; Ma, Chao; Liu, Weihong; Liu, Hongxu; Wang, Ning; Kang, Qunfu; Li, Ping

2015-09-01

Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a special AT1 antagonist, can dilate blood vessels and reduce blood pressure, but it remained unclear whether valsartan can promote the stability of atherosclerotic plaque by affecting renalase. This study examined the tissue distribution of renalase in ApoE(-/-) mice fed with a high-fat diet and the effect of valsartan on expression of renalase. ApoE(-/-) mice were fed with a high-fat diet for 13 or 26 weeks. As a control, 10 C57BL mice were fed with a standard chow diet. After 13 weeks on the high-fat diet, the ApoE(-/-) mice were randomized (10 mice/group) and treated with valsartan, simvastatin, or distilled water (control group) for an additional 13 weeks accompanied by a high-fat diet. Knockout of ApoE caused a dramatic increase in expression of renalase in mice adipose tissue. With the disturbance of lipid metabolism induced by a high-fat diet, renalase expression decreased in the liver. Renalase can be expressed in smooth muscle cells and M2 macrophages in atherosclerotic plaque, and its expression gradually decreases in the fibrous cap during the transition from stable to vulnerable atherosclerotic plaque. Valsartan, an AT1 receptor antagonist, promotes the stabilization of atherosclerotic plaque by increasing the levels of renalase in serum and the expression of renalase in the fibrous cap of atherosclerotic plaque. It also reduces triglyceride levels in serum and increases the expression of renalase in the liver. Renalase may be a potential-related gene of lipid metabolism and As, and it may be the possible molecular target of valsartan to help stabilize atherosclerotic plaque. © The Author(s) 2015.

16S rRNA-based detection of oral pathogens in coronary atherosclerotic plaque

Directory of Open Access Journals (Sweden)

Mahendra Jaideep

2010-01-01

Full Text Available Background: Atherosclerosis develops as a response of the vessel wall to injury. Chronic bacterial infections have been associated with an increased risk for atherosclerosis and coronary artery disease. The ability of oral pathogens to colonize in coronary atheromatous plaque is well known. Aim: The aim of this study was to detect the presence of Treponema denticola, Porphyromonas gingivalis and Campylobacter rectus in the subgingival and atherosclerotic plaques of patients with coronary artery disease. Materials and Methods: Fifty-one patients in the age group of 40-80 years with coronary artery disease were selected for the study. DNA was extracted from the plaque samples. The specific primers for T. denticola, C. rectus and P. gingivalis were used to amplify a part of the 16S rRNA gene by polymerase chain reaction. Statistical Analysis Used: Chi-square analysis, correlation coefficient and prevalence percentage of the microorganisms were carried out for the analysis. Results: Of the 51 patients, T. denticola, C. rectus and P. gingivalis were detected in 49.01%, 21.51% and 45.10% of the atherosclerotic plaque samples. Conclusions: Our study revealed the presence of bacterial DNA of the oral pathogenic microorganisms in coronary atherosclerotic plaques. The presence of the bacterial DNA in the coronary atherosclerotic plaques in significant proportion may suggest the possible relationship between periodontal bacterial infection and genesis of coronary atherosclerosis.

Control of atherosclerotic plaque vulnerability: insights from transgenic mice

NARCIS (Netherlands)

Heeneman, Sylvia; Lutgens, Esther; Schapira, Kitty B.; Daemen, Mat J. A. P.; Biessen, Erik A. L.

2008-01-01

Atherosclerosis is a complex, progressive disease of the large systemic arteries. This multi-factorial disease is characterized by accumulation of lipids, cells and extracellular matrix in the vessel wall. The quest to unravel the molecular mechanisms leading to progression of human atherosclerotic

Decreased Regulatory T Cells in Vulnerable Atherosclerotic Lesions: Imbalance between Pro- and Anti-Inflammatory Cells in Atherosclerosis

Directory of Open Access Journals (Sweden)

Ilonka Rohm

2015-01-01

Full Text Available Atherosclerosis is a chronic inflammatory disease of the arterial wall in which presentation of autoantigens by dendritic cells (DCs leads to the activation of T cells. Anti-inflammatory cells like Tregs counterbalance inflammation in atherogenesis. In our study, human carotid plaque specimens were classified as stable (14 and unstable (15 according to established morphological criteria. Vessel specimens (n=12 without any signs of atherosclerosis were used as controls. Immunohistochemical staining was performed to detect different types of DCs (S100, fascin, CD83, CD209, CD304, and CD123, proinflammatory T cells (CD3, CD4, CD8, and CD161, and anti-inflammatory Tregs (FoxP3. The following results were observed: in unstable lesions, significantly higher numbers of proinflammatory cells like DCs, T helper cells, cytotoxic T cells, and natural killer cells were detected compared to stable plaques. Additionally, there was a significantly higher expression of HLA-DR and more T cell activation (CD25, CD69 in unstable lesions. On the contrary, unstable lesions contained significantly lower numbers of Tregs. Furthermore, a significant inverse correlation between myeloid DCs and Tregs was shown. These data suggest an increased inflammatory state in vulnerable plaques resulting from an imbalance of the frequency of local pro- and anti-inflammatory immune cells.

Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression.

Directory of Open Access Journals (Sweden)

Kevin J Woollard

Full Text Available Soluble P-selectin (sP-selectin, a biomarker of inflammatory related pathologies including cardiovascular and peripheral vascular diseases, also has pro-atherosclerotic effects including the ability to increase leukocyte recruitment and modulate thrombotic responses in vivo. The current study explores its role in progressing atherosclerotic plaque disease. Apoe-/- mice placed on a high fat diet (HFD were given daily injections of recombinant dimeric murine P-selectin (22.5 µg/kg/day for 8 or 16 weeks. Saline or sE-selectin injections were used as negative controls. In order to assess the role of sP-selectin on atherothrombosis an experimental plaque remodelling murine model, with sm22α-hDTR Apoe-/- mice on a HFD in conjunction with delivery of diphtheria toxin to induce targeted vascular smooth muscle apoptosis, was used. These mice were similarly given daily injections of sP-selectin for 8 or 16 weeks. While plaque mass and aortic lipid content did not change with sP-selectin treatment in Apoe-/- or SM22α-hDTR Apoe-/- mice on HFD, increased plasma MCP-1 and a higher plaque CD45 content in Apoe-/- HFD mice was observed. As well, a significant shift towards a more unstable plaque phenotype in the SM22α-hDTR Apoe-/- HFD mice, with increased macrophage accumulation and lower collagen content, leading to a lower plaque stability index, was observed. These results demonstrate that chronically raised sP-selectin favours progression of an unstable atherosclerotic plaque phenotype.

F-18 fluoride positron emission tomography-computed tomography for detecting atherosclerotic plaques

International Nuclear Information System (INIS)

Kang, Won Jun

2015-01-01

A large number of major cardiovascular events occur in patients due to minimal or some lumen narrowing of the coronary artery. Recent biological studies have shown that the biological composition or vulnerability of the plaque is more critical for plaque rupture compared to the degree of stenosis. To overcome the limitations of anatomical images, molecular imaging techniques have been suggested as promising imaging tools in various fields. F-18 fluorodeoxyglucose (FDG), which is widely used in the field of oncology, is an example of molecular probes used in atherosclerotic plaque evaluation. FDG is a marker of plaque macrophage glucose utilization and inflammation, which is a prominent characteristic of vulnerable plaque. Recently, F-18 fluoride has been used to visualize vulnerable plaque in clinical studies. F-18 fluoride accumulates in regions of active microcalcification, which is normally observed during the early stages of plaque formation. More studies are warranted on the accumulation of F-18 fluoride and plaque formation/vulnerability; however, due to high specific accumulation, low background activity, and easy accessibility, F-18 fluoride is emerging as a promising non-invasive imaging probe to detect vulnerable plaque

F-18 fluoride positron emission tomography-computed tomography for detecting atherosclerotic plaques

Energy Technology Data Exchange (ETDEWEB)

Kang, Won Jun [Dept. of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2015-12-15

A large number of major cardiovascular events occur in patients due to minimal or some lumen narrowing of the coronary artery. Recent biological studies have shown that the biological composition or vulnerability of the plaque is more critical for plaque rupture compared to the degree of stenosis. To overcome the limitations of anatomical images, molecular imaging techniques have been suggested as promising imaging tools in various fields. F-18 fluorodeoxyglucose (FDG), which is widely used in the field of oncology, is an example of molecular probes used in atherosclerotic plaque evaluation. FDG is a marker of plaque macrophage glucose utilization and inflammation, which is a prominent characteristic of vulnerable plaque. Recently, F-18 fluoride has been used to visualize vulnerable plaque in clinical studies. F-18 fluoride accumulates in regions of active microcalcification, which is normally observed during the early stages of plaque formation. More studies are warranted on the accumulation of F-18 fluoride and plaque formation/vulnerability; however, due to high specific accumulation, low background activity, and easy accessibility, F-18 fluoride is emerging as a promising non-invasive imaging probe to detect vulnerable plaque.

Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile.

Science.gov (United States)

Merghani, Ahmed; Maestrini, Viviana; Rosmini, Stefania; Cox, Andrew T; Dhutia, Harshil; Bastiaenan, Rachel; David, Sarojini; Yeo, Tee Joo; Narain, Rajay; Malhotra, Aneil; Papadakis, Michael; Wilson, Mathew G; Tome, Maite; AlFakih, Khaled; Moon, James C; Sharma, Sanjay

2017-07-11

Studies in middle-age and older (masters) athletes with atherosclerotic risk factors for coronary artery disease report higher coronary artery calcium (CAC) scores compared with sedentary individuals. Few studies have assessed the prevalence of coronary artery disease in masters athletes with a low atherosclerotic risk profile. We assessed 152 masters athletes 54.4±8.5 years of age (70% male) and 92 controls of similar age, sex, and low Framingham 10-year coronary artery disease risk scores with an echocardiogram, exercise stress test, computerized tomographic coronary angiogram, and cardiovascular magnetic resonance imaging with late gadolinium enhancement and a 24-hour Holter. Athletes had participated in endurance exercise for an average of 31±12.6 years. The majority (77%) were runners, with a median of 13 marathon runs per athlete. Most athletes (60%) and controls (63%) had a normal CAC score. Male athletes had a higher prevalence of atherosclerotic plaques of any luminal irregularity (44.3% versus 22.2%; P =0.009) compared with sedentary males, and only male athletes showed a CAC ≥300 Agatston units (11.3%) and a luminal stenosis ≥50% (7.5%). Male athletes demonstrated predominantly calcific plaques (72.7%), whereas sedentary males showed predominantly mixed morphology plaques (61.5%). The number of years of training was the only independent variable associated with increased risk of CAC >70th percentile for age or luminal stenosis ≥50% in male athletes (odds ratio, 1.08; 95% confidence interval, 1.01-1.15; P =0.016); 15 (14%) male athletes but none of the controls revealed late gadolinium enhancement on cardiovascular magnetic resonance imaging. Of these athletes, 7 had a pattern consistent with previous myocardial infarction, including 3(42%) with a luminal stenosis ≥50% in the corresponding artery. Most lifelong masters endurance athletes with a low atherosclerotic risk profile have normal CAC scores. Male athletes are more likely to have a CAC

Moderate overweight is beneficial and severe obesity detrimental for patients with documented atherosclerotic heart disease

DEFF Research Database (Denmark)

Azimi, Aziza; Charlot, Mette Gitz; Torp-Pedersen, Christian

2013-01-01

Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease.......Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease....

Histological Characteristics of Intracranial Atherosclerosis in a Chinese Population: A Postmortem Study

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Wen Jie Yang

2017-09-01

Full Text Available BackgroundAnterior and posterior circulation atherosclerosis differ in vascular risk factors and stroke mechanisms. However, few studies have compared the pathological features between these lesions. Using a series of intracranial artery specimens, we characterized the intracranial atherosclerotic lesions and compared pathological features among different arteries of the intracranial vasculature.MethodsIntracranial large arteries of 32 consecutively recruited autopsy cases of Chinese adults aged 45 years or older were examined pathologically using routine histology and immunostaining, to characterize the pathological features of the atherosclerotic lesions. We analyzed middle cerebral arteries (MCAs (both left and right, vertebral arteries (VAs (side more affected, and basilar arteries (BAs.ResultsProgressive atherosclerotic lesions were present in 91(71% of the 128 arteries examined. Features of complicated plaques were infrequently detected: plaque hemorrhage was encountered in 12%, neovasculature in 12%, lumen thrombi in 13%, macrophage infiltration in 20%, and calcification in 25% of arteries. Luminal narrowing of MCA was the most severe, followed by VA; the BA least stenotic (37 ± 25 vs. 30 ± 24 vs. 20 ± 20%, all p < 0.05. MCA had more eccentric (vs. concentric plaques than VA (69 vs. 25%, p = 0.003 and BA (69 vs. 38%; p = 0.03. Lumen thrombi were more frequent in BA, and calcification most commonly occurred in VA atherosclerotic lesions.ConclusionIntracranial atherosclerotic plaques were commonly present in this sample, but the lesions generally lacked features of complicated plaques. MCA lesions had demonstrable differences compared with VA and BA lesions. Further studies are needed to determine whether these characteristics indicate a distinctive atherosclerotic phenotype for the intracranial vasculature.

High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

Science.gov (United States)

Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

2016-02-01

Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

Molecular dynamics of formation of TD lesioned DNA complexed with repair enzyme - onset of the enzymatic repair process

Energy Technology Data Exchange (ETDEWEB)

Pinak, Miroslav [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

1999-12-01

To describe the first step of the enzymatic repair process (formation of complex enzyme-DNA), in which the thymine dimer (TD) part is removed from DNA, the 500 picosecond (ps) molecular dynamics (MD) simulation of TD lesioned DNA and part of repair enzyme cell (inclusive of catalytic center - Arg-22, Glu-23, Arg-26 and Thr-2) was performed. TD is UV originated lesion in DNA and T4 Endonuclease V is TD specific repair enzyme. Both molecules were located in the same simulation cell and their relative movement was examined. During the simulation the research was focused on the role of electrostatic energy in formation of complex enzyme-DNA. It is found, that during the first 100 ps of MD, the part of enzyme approaches the DNA surface at the TD lesion, interacts extensively by electrostatic and van der Walls interactions with TD part of DNA and forms complex that lasts stabile for 500 ps of MD. In the beginning of MD, the positive electrostatic interaction energy between part of enzyme and TD ({approx} +10 kcal/mol) drives enzyme towards the DNA molecule. Water-mediated hydrogen bonds between enzyme and DNA help to keep complex stabile. As a reference, the MD simulation of the identical system with native DNA molecule (two native thymines (TT) instead of TD) was performed. In this system the negative electrostatic interaction energy between part of enzyme and TT ({approx} -11 kcal/mol), in contrary to the positive one in the system with TD, doesn't drive enzyme towards DNA and complex is not formed. (author)

Molecular dynamics of formation of TD lesioned DNA complexed with repair enzyme - onset of the enzymatic repair process

International Nuclear Information System (INIS)

Pinak, Miroslav

1999-12-01

To describe the first step of the enzymatic repair process (formation of complex enzyme-DNA), in which the thymine dimer (TD) part is removed from DNA, the 500 picosecond (ps) molecular dynamics (MD) simulation of TD lesioned DNA and part of repair enzyme cell (inclusive of catalytic center - Arg-22, Glu-23, Arg-26 and Thr-2) was performed. TD is UV originated lesion in DNA and T4 Endonuclease V is TD specific repair enzyme. Both molecules were located in the same simulation cell and their relative movement was examined. During the simulation the research was focused on the role of electrostatic energy in formation of complex enzyme-DNA. It is found, that during the first 100 ps of MD, the part of enzyme approaches the DNA surface at the TD lesion, interacts extensively by electrostatic and van der Walls interactions with TD part of DNA and forms complex that lasts stabile for 500 ps of MD. In the beginning of MD, the positive electrostatic interaction energy between part of enzyme and TD (∼ +10 kcal/mol) drives enzyme towards the DNA molecule. Water-mediated hydrogen bonds between enzyme and DNA help to keep complex stabile. As a reference, the MD simulation of the identical system with native DNA molecule (two native thymines (TT) instead of TD) was performed. In this system the negative electrostatic interaction energy between part of enzyme and TT (∼ -11 kcal/mol), in contrary to the positive one in the system with TD, doesn't drive enzyme towards DNA and complex is not formed. (author)

Role of Rab5 in the formation of macrophage-derived foam cell.

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Chan, Lokwern; Hong, Jin; Pan, Junjie; Li, Jian; Wen, Zhichao; Shi, Haiming; Ding, Jianping; Luo, Xinping

2017-09-12

Foam cells play a key role in the occurrence and pathogenesis of atherosclerosis. Its formation starts with the ingestion of oxidized low-density lipoprotein (oxLDL). The process is associated with Ras related protein in brain 5 (Rab5) which plays a critical role in regulating endocytosis and early endosomal trafficking. Base on this, we presumed that Rab5 might participate in the maturation of foam cell. The aim of this study is to investigate the effect of Rab5 on macrophage cholesterol during the evolvement of macrophage when induced by oxLDL to the formation of foam cell. Immunohistochemistry was performed to analyze the distribution of macrophages and Rab5 in atherosclerotic plaque. RNA inteference study and transfection of inactive mutant (GFP-Rab5-S34N) and active mutant (GFP-Rab5-Q79L) in U937-derived macrophage were utilized to investigate the impact of Rab5 on the process of macrophage cholesterol, which could be detected by oil red O staining, determination of intracellular lipid content, filipin staining, nile red staining and the costaining of early endosome antigen-1 (EEA-1) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylin dicarbocyanine (Dil)-labelled oxLDL (Dil-oxLDL). Rab5 was found abundantly localized in macrophage rich areas of human atherosclerotic lesions. On the foam cell study, the expression of Rab5 was increased after the incubation of oxLDL. The inteference study indicated the depletion of Rab5 led to the decreases of oil red O staining areas, total cholesterol and cholesterol esters in U937-derived marophages. Moreover, the fluorescence intensity of filipin and nile red staining were lower in GFP-Rab5-S34N as compared with GFP-Rab5-Q79L. The confocal study demonstrated less Dil-oxLDL was internalized in GFP-Rab5-S34N as compared with GFP-Rab5-Q79L; the result showed also the decrease in colocalization of internalized Dil-oxLDL and EEA-1 for GFP-Rab5-S34N as compared with GFP-Rab5-Q79L. Rab5 plays an important role in modulating the

Imaging of hypoxia in mouse atherosclerotic plaques with 64Cu-ATSM

International Nuclear Information System (INIS)

Nie, Xingyu; Randolph, Gwendalyn J.; Elvington, Andrew; Bandara, Nilantha; Zheleznyak, Alexander; Gropler, Robert J.; Woodard, Pamela K.; Lapi, Suzanne E.

2016-01-01

Introduction: Cardiovascular disease is the leading cause of death in the United States. The identification of vulnerable plaque at risk of rupture has been a major focus of research. Hypoxia has been identified as a potential factor in the formation of vulnerable plaque, and it is clear that decreased oxygen plays a role in the development of plaque angiogenesis leading to plaque destabilization. The purpose of this study is to demonstrate the feasibility of copper-64 labeled diacetyl-bis (N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), a positron-emitting radiopharmaceutical taken up in low-oxygen-tension cells, for the identification of hypoxic and potentially unstable atherosclerotic plaque in a mouse model. Methods: 64 Cu-ATSM PET was performed in 21 atherosclerotic apolipoprotein E knockout (ApoE −/− ) mice, 6 of which were fed high-fat diet (HFD) while the others received standard-chow diet (SCD), and 13 control wild type mice fed SCD. 4 SCD ApoE −/− mice and 4 SCD wild type mice also underwent 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) imaging one day prior to 64 Cu-ATSM PET. Results: 64 Cu-ATSM uptake was increased in the aortic arch in SCD ApoE −/− mice (average aortic arch/muscle (A/M) standardized uptake value ratio 7.5–30 min post injection: (5.66 ± 0.23) compared to control mice (A/M SUV ratio 7.5–30 min post injection (3.87 ± 0.22), p < 0.0001). HFD ApoE −/− mice also showed similarly increased aortic arch uptake on PET imaging in comparison to control mice. Immunohistochemistry in both HFD and SCD ApoE −/− mice revealed noticeable hypoxia by pimonidazole stain in atherosclerosis which was co-localized to macrophage by CD68 staining. Autoradiography assessment demonstrated the presence of hypoxia by 64 Cu-ATSM uptake correlated with pimonidazole uptake within the ex vivo atherosclerotic aortic arch specimens. A significant increase in 18 F-FDG uptake in the SCD ApoE −/− mice in comparison to

Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice.

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Li, Melissa W; Mian, Muhammad Oneeb Rehman; Barhoumi, Tlili; Rehman, Asia; Mann, Koren; Paradis, Pierre; Schiffrin, Ernesto L

2013-10-01

Endothelin (ET)-1 plays a role in vascular reactive oxygen species production and inflammation. ET-1 has been implicated in human atherosclerosis and abdominal aortic aneurysm (AAA) development. ET-1 overexpression exacerbates high-fat diet-induced atherosclerosis in apolipoprotein E(-/-) (Apoe(-/-)) mice. ET-1-induced reactive oxygen species and inflammation may contribute to atherosclerosis progression and AAA development. Eight-week-old male wild-type mice, transgenic mice overexpressing ET-1 selectively in endothelium (eET-1), Apoe(-/-) mice, and eET-1/Apoe(-/-) mice were fed high-fat diet for 8 weeks. eET-1/Apoe(-/-) had a 45% reduction in plasma high-density lipoprotein (P<0.05) and presented ≥ 2-fold more aortic atherosclerotic lesions compared with Apoe(-/-) (P<0.01). AAAs were detected only in eET-1/Apoe(-/-) (8/21; P<0.05). Reactive oxygen species production was increased ≥ 2-fold in perivascular fat, media, or atherosclerotic lesions in the ascending aorta and AAAs of eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). Monocyte/macrophage infiltration was enhanced ≥ 2.5-fold in perivascular fat of ascending aorta and AAAs in eET-1/Apoe(-/-) compared with Apoe(-/-) (P<0.05). CD4(+) T cells were detected almost exclusively in perivascular fat (3/6) and atherosclerotic lesions (5/6) in ascending aorta of eET-1/Apoe(-/-) (P<0.05). The percentage of spleen proinflammatory Ly-6C(hi) monocytes was enhanced 26% by ET-1 overexpression in Apoe(-/-) (P<0.05), and matrix metalloproteinase-2 was increased 2-fold in plaques of eET-1/Apoe(-/-) (P<0.05) compared with Apoe(-/-). ET-1 plays a role in progression of atherosclerosis and AAA formation by decreasing high-density lipoprotein, and increasing oxidative stress, inflammatory cell infiltration, and matrix metalloproteinase-2 in perivascular fat, vascular wall, and atherosclerotic lesions.

Monitoring the lesion formation during histotripsy treatment using shear wave imaging

Science.gov (United States)

Arnal, Bastien; Lee, Wei-Ning; Pernot, Mathieu; Fink, Mathias; Tanter, Mickael

2012-11-01

Monitoring the lesion formation induced by histotripsy has mainly relied on the quantitative change in backscatter intensity using ultrasound B-mode imaging. However, how the mechanical properties of the histotripsy-treated tissue region alter during the procedure is yet to be fully investigated. We thus proposed here to monitor such a therapeutic process based on shear modulus estimated by shear wave imaging (SWI). In the therapeutic procedure, a single-element piezo-composite focused transducer (Imasonic, Besançon, France) with a center frequency of 660 kHz, a focal length of 45 mm, and an fnumber of 1 was driven by a function generator (AFG 3101, Tektronix, Beaverton, OR) and a gated RF power amplifier (GA-2500A, RITEC Inc., USA) to generate ultrasound histotripsy pulses. Histotripsy pulses were delivered for 20 seconds and then followed by a 30-second pause and a rapid monitoring step. Such a treatment and monitoring scheme was repeated for 10 mins. Both the reference measurement and monitoring were realized by SWI, where plane shear waves were generated by an 8 MHz linear array probe connected to a prototype ultrasound scanner, and acquired at a frame rate of 10000 Hz. Shear modulus was estimated and mapped in 2D through a time-of-flight algorithm. Gelatin (8%)-agar (2%) phantoms and ex-vivo porcine liver samples were tested. Regions of interests (ROI's) of 2 mm-by-2 mm in both untreated and treated regions were selected to compute the contrast-to-noise ratio (CNR). In all three scenarios where different PD's and PRF's were implemented, during the first 100 seconds of the treatment, 50% decrease in the shear modulus within the histotripsy-targeted zone was already observed, and the CNR of the shear modulus increased by 18 dB. In contrast, the backscatter intensity began to reduce and the corresponding CNR was found to increase by 6 dB only after 120 seconds of treatment. The results demonstrated that SWI can map quantitatively the change of mechanical

Lysophosphatidic acid directly induces macrophage-derived foam cell formation by blocking the expression of SRBI.

Science.gov (United States)

Chen, Linmu; Zhang, Jun; Deng, Xiao; Liu, Yan; Yang, Xi; Wu, Qiong; Yu, Chao

2017-09-23

The leading cause of morbidity and mortality is the result of cardiovascular disease, mainly atherosclerosis. The formation of macrophage foam cells by ingesting ox-LDL and focal retention in the subendothelial space are the hallmarks of the early atherosclerotic lesion. Lysophosphatidic acid (LPA), which is a low-molecular weight lysophospholipid enriched in oxidized LDL, exerts a range of effects on the cardiovascular system. Previous reports show that LPA increases the uptake of ox-LDL to promote the formation of foam cells. However, as the most active component of ox-LDL, there is no report showing whether LPA directly affects foam cell formation. The aim of this study was to investigate the effects of LPA on foam cell formation, as well as to elucidate the underlying mechanism. Oil red O staining and a Cholesterol/cholesteryl ester quantitation assay were used to evaluate foam cell formation in Raw264.7 macrophage cells. We utilized a Western blot and RT-PCR to investigate the relationship between LPA receptors and lipid transport related proteins. We found that LPA promoted foam cell formation, using 200 μM for 24 h. Meanwhile, the expression of the Scavenger receptor BI (SRBI), which promotes the efflux of free cholesterol, was decreased. Furthermore, the LPA 1/3 receptor antagonist Ki16425 significantly abolished the LPA effects, indicating that LPA 1/3 was involved in the foam cell formation and SRBI expression induced by LPA. Additionally, the LPA-induced foam cell formation was blocked with an AKT inhibitor. Our results suggest that LPA-enhanced foam cell formation is mediated by LPA 1/3 -AKT activation and subsequent SRBI expression. Copyright © 2017. Published by Elsevier Inc.

Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques

International Nuclear Information System (INIS)

Kuge, Yuji; Takai, Nozomi; Ogawa, Yuki; Temma, Takashi; Nishigori, Kantaro; Ishino, Seigo; Kamihashi, Junko; Saji, Hideo; Zhao, Yan; Kiyono, Yasushi; Shiomi, Masashi

2010-01-01

Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of 99m Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG 3 and negative control IgG 3 were radiolabelled with 99m Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield 99m Tc-MT1-MMP mAb and 99m Tc-IgG 3 , respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed. 99m Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional 99m Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p 99m Tc-IgG 3 accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest 99m Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 ± 1.9, %ID x BW/mm 2 x 10 2 ), followed in decreasing order by fibroatheromatous (1.8 ± 1.3), collagen-rich (1.6 ± 1.0) and neointimal lesions (1.5 ± 1.5). In contrast, 99m Tc-IgG 3 accumulation was almost independent of the histological grade of lesions. Higher 99m Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with 99m Tc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required. (orig.)

Evaluation of texture parameters for the quantitative description of multimodal nonlinear optical images from atherosclerotic rabbit arteries

Energy Technology Data Exchange (ETDEWEB)

Mostaco-Guidolin, Leila B; Ko, Alex C-T; Popescu, Dan P; Smith, Michael S D; Kohlenberg, Elicia K; Sowa, Michael G [Institute for Biodiagnostics, National Research Council Canada, Winnipeg, R3B 1Y6 (Canada); Shiomi, Masashi [Institute of Experimental Animals, School of Medicine, Kobe University, Kobe 650-0017 (Japan); Major, Arkady [Department Electrical and Computer Engineering, University of Manitoba, E3-559 Engineering Building, Winnipeg, R3T 5V6 (Canada)

2011-08-21

The composition and structure of atherosclerotic lesions can be directly related to the risk they pose to the patient. Multimodal nonlinear optical (NLO) microscopy provides a powerful means to visualize the major extracellular components of the plaque that critically determine its structure. Textural features extracted from NLO images were investigated for their utility in providing quantitative descriptors of structural and compositional changes associated with plaque development. Ten texture parameters derived from the image histogram and gray level co-occurrence matrix were examined that highlight specific structural and compositional motifs that distinguish early and late stage plaques. Tonal-texture parameters could be linked to key histological features that characterize vulnerable plaque: the thickness and density of the fibrous cap, size of the atheroma, and the level of inflammation indicated through lipid deposition. Tonal and texture parameters from NLO images provide objective metrics that correspond to structural and biochemical changes that occur within the vessel wall in early and late stage atherosclerosis.

Distribution and natural course of intracranial vessel wall lesions in patients with ischemic stroke or TIA at 7.0 tesla MRI

Energy Technology Data Exchange (ETDEWEB)

Kolk, Anja G. van der; Luijten, Peter R.; Hendrikse, Jeroen [University Medical Center Utrecht, Department of Radiology, Postbox 85500, Utrecht (Netherlands); Zwanenburg, Jaco J.M. [University Medical Center Utrecht, Department of Radiology, Postbox 85500, Utrecht (Netherlands); University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Brundel, Manon; Biessels, Geert Jan [University Medical Center Utrecht, Department of Neurology, Utrecht (Netherlands); Visser, Fredy [University Medical Center Utrecht, Department of Radiology, Postbox 85500, Utrecht (Netherlands); Philips Healthcare, Best (Netherlands)

2015-06-01

Previous studies using intracranial vessel wall MRI techniques showed that over 50 % of patients with ischemic stroke or TIA had one or more intracranial vessel wall lesions. In the current study, we assessed the preferential location of these lesions within the intracranial arterial tree and their potential changes over time in these patient groups. Forty-nine patients with ischemic stroke (n = 25) or TIA (n = 24) of the anterior cerebral circulation underwent 7.0 T MRI, including a T{sub 1}-weighted magnetization-preparation inversion recovery turbo-spin-echo (MPIR-TSE) sequence within one week and approximately one month after symptom onset. Intracranial vessel wall lesions were scored for multiple locations within the arterial tree and differences between one-week and one-month images. At baseline, 132 intracranial vessel wall lesions were found in 41 patients (84 %), located primarily in the anterior cerebral circulation (74 %), with a preferential location in the distal internal carotid artery and M1 and M2 segments of the middle cerebral artery. During follow-up, presence or enhancement patterns changed in 14 lesions (17 %). A large burden of intracranial vessel wall lesions was found in both the anterior and posterior cerebral circulation. Most lesions were found to be relatively stable, possibly indicating a more generalized atherosclerotic process. (orig.)

Feasibility of simultaneous PET/MR in diet-induced atherosclerotic minipig

DEFF Research Database (Denmark)

Pedersen, Sune F; Ludvigsen, Trine P; Johannesen, Helle H

2014-01-01

Novel hybrid 18-fluoro-deoxy-D-glucose ((18)F-FDG) based positron emission tomography (PET) and magnetic resonance imaging (MRI) has shown promise for characterization of atherosclerotic plaques clinically. The purpose of this study was to evaluate the method in a pre-clinical model of diet......-induced atherosclerosis, based on the Göttingen minipig. Using (18)F-FDG PET/MRI the goal was to develop and create a new imaging method in an in vivo animal model for translational studies of atherosclerosis. We used a strategy of multisequence MRI for optimal anatomical imaging of the abdominal aortas of the pigs (n=4...... glycolysis as given by standardized uptake values (SUV). Ex vivo en face evaluation of aortas from an atherosclerotic animal illustrated plaque distribution macroscopically, compared to a lean control animal. Although T2-TSE weighted imaging was most consistent, no one MRI sequence was preferable...

A computational evaluation of sedentary lifestyle effects on carotid hemodynamics and atherosclerotic events incidence.

Science.gov (United States)

Caruso, Maria Vittoria; Serra, Raffaele; Perri, Paolo; Buffone, Gianluca; Caliò, Francesco Giuseppe; DE Franciscis, Stefano; Fragomeni, Fragomeni

2017-01-01

Hemodynamics has a key role in atheropathogenesis. Indeed, atherosclerotic phenomena occur in vessels characterized by complex geometry and flow pattern, like the carotid bifurcation. Moreover, lifestyle is a significant risk factor. The aim of this study is to evaluate the hemodynamic effects due to two sedentary lifestyles - sitting and standing positions - in the carotid bifurcation in order to identify the worst condition and to investigate the atherosclerosis incidence. The computational fluid dynamics (CFD) was chosen to carry out the analysis, in which in vivo non-invasive measurements were used as boundary conditions. Furthermore, to compare the two conditions, one patient-specific 3D model of a carotid bifurcation was reconstructed starting from computer tomography. Different mechanical indicators, correlated with atherosclerosis incidence, were calculated in addition to flow pattern and pressure distribution: the time average wall shear stress (TAWSS), the oscillatory shear index (OSI) and the relative residence time (RRT). The results showed that the bulb and the external carotid artery emergence are the most probable regions in which atherosclerotic events could happen. Indeed, low velocity and WSS values, high OSI and, as a consequence, areas with chaotic-swirling flow, with stasis (high RRT), occur. Moreover, the sitting position is the worst condition: considering a cardiac cycle, TAWSS is less than 17.2% and OSI and RRT are greater than 17.5% and 21.2%, respectively. This study suggests that if a person spends much time in the sitting position, a high risk of plaque formation and, consequently, of stenosis could happen.

Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels: implication in the pathogenesis of Alzheimer's disease.

Science.gov (United States)

Aliev, Gjumrakch; Gasimov, Eldar; Obrenovich, Mark E; Fischbach, Kathryn; Shenk, Justin C; Smith, Mark A; Perry, George

2008-01-01

The pathogenesis that is primarily responsible for Alzheimer's disease (AD) and cerebrovascular accidents (CVA) appears to involve chronic hypoperfusion. We studied the ultrastructural features of vascular lesions and mitochondria in brain vascular wall cells from human AD biopsy samples and two transgenic mouse models of AD, yeast artificial chromosome (YAC) and C57B6/SJL Tg (+), which overexpress human amyloid beta precursor protein (AbetaPP). In situ hybridization using probes for normal and 5 kb deleted human and mouse mitochondrial DNA (mtDNA) was performed along with immunocytochemistry using antibodies against the Abeta peptide processed from AbetaPP, 8-hydroxy-2'-guanosine (8OHG), and cytochrome c oxidase (COX). More amyloid deposition, oxidative stress markers as well as mitochondrial DNA deletions and structural abnormalities were present in the vascular walls of the human AD samples and the AbetaPP-YAC and C57B6/SJL Tg (+) transgenic mice compared to age-matched controls. Ultrastructural damage in perivascular cells highly correlated with endothelial lesions in all samples. Therefore, pharmacological interventions, directed at correcting the chronic hypoperfusion state, may change the natural course of the development of dementing neurodegeneration.

Experimental study of multi-slice CT for the evaluation of atherosclerotic plaques

International Nuclear Information System (INIS)

Tang Xiang; Lv Bin; Wu Wenhui; Lu Jinguo; Dai Ruping; Bai Hua; Tang Yue; Lv Fengying; Jiang Shiliang

2009-01-01

Objective: To evaluate the diagnostic values of MSCT for detecting atherosclerotic plaques on New Zealand rabbits models in comparison with pathologic results. Methods: Fifteen New Zealand rabbits were enrolled in this study, including 5 with balloon injury and high-fat diet (group A), 5 with high-fat diet only (group B) and 5 with regular feed (group C). 16th week late, contrast-enhanced MSCT scan was performed in all rabbits with 16 slice MSCT (16-MSCT) in group A and 64 slice MSCT (64-MSCT) in group B and C. The CT and pathological findings were compared in a double-blind manner. The sensitivities and specificities of 16-MSCT and 64-MSCT for detecting atherosclerotic plaques were evaluated by using Fisher test and χ 2 test. Results: Sixty and seventy-five images on 16-MSCT and 64-MSCT had corresponding pathological slices. The sensitivities for the detection of plaques on 16-MSCT and 64-MSCT were 41.5% (22/53) and 64.9% (24/37), and specificities of 85.7% (6/7) and 89.5% (34/38), respectively. Conclusions: 64-MSCT has a higher sensitivity in the detection of atherosclerotic plaques than 16-MSCT. Both scanners can be used to preclude the diagnosis of atherosclerosis. (authors)

Mechanical properties of human atherosclerotic intima tissue.

Science.gov (United States)

Akyildiz, Ali C; Speelman, Lambert; Gijsen, Frank J H

2014-03-03

Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease

DEFF Research Database (Denmark)

Nordestgaard, Børge G

2016-01-01

Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need.......1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate...

The complex fate in plasma of gadolinium incorporated into high-density lipoproteins used for magnetic imaging of atherosclerotic plaques

NARCIS (Netherlands)

Barazza, Alessandra; Blachford, Courtney; Even-Or, Orli; Joaquin, Victor A.; Briley-Saebo, Karen C.; Chen, Wei; Jiang, Xian-Cheng; Mulder, Willem J. M.; Cormode, David P.; Fayad, Zahi A.; Fisher, Edward A.

2013-01-01

We have previously reported enhancing the imaging of atherosclerotic plaques in mice using reconstituted high density lipoproteins (HDL) as nanocarriers for the MRI contrast agent gadolinium (Gd). This study focuses on the underlying mechanisms of Gd delivery to atherosclerotic plaques. HDL, LDL,

Association between diabetes and different components of coronary atherosclerotic plaque burden as measured by coronary multidetector computed tomography.

Science.gov (United States)

Yun, Chun-Ho; Schlett, Christopher L; Rogers, Ian S; Truong, Quynh A; Toepker, Michael; Donnelly, Patrick; Brady, Thomas J; Hoffmann, Udo; Bamberg, Fabian

2009-08-01

The aim of the study was to assess differences in the presence, extent, and composition of coronary atherosclerotic plaque burden as detected by coronary multidetector computed tomography (MDCT) between patients with and without diabetes mellitus. We compared coronary atherosclerotic plaques (any plaque, calcified [CAP], non-calcified [NCAP, and mixed plaque [MCAP

Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export

DEFF Research Database (Denmark)

Kjølby, Mads Fuglsang; Andersen, Olav Michael; Breiderhoff, Tilman

2010-01-01

of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic...... lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3. Udgivelsesdato: september 8...

Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

DEFF Research Database (Denmark)

Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard

2012-01-01

Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and ...

The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine

Directory of Open Access Journals (Sweden)

Saskia J. H. Brinkmann

2015-05-01

Full Text Available Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS and thereby nitric oxide (NO, respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9, standard rabbit chow plus atorvastatin (group S, n = 8, standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8 or standard rabbit chow (group C, n = 9 as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.

Comparison between MDCT and Grayscale IVUS in a Quantitative Analysis of Coronary Lumen in Segments with or without Atherosclerotic Plaques

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Falcão, João L. A. A.; Falcão, Breno A. A. [Heart Institute (InCor), University of São Paulo Medical School (USP), São Paulo, SP (Brazil); Gurudevan, Swaminatha V. [Cedars-Sinai Heart Institute, Los Angeles, California, USA (United States); Campos, Carlos M.; Silva, Expedito R.; Kalil-Filho, Roberto; Rochitte, Carlos E.; Shiozaki, Afonso A.; Coelho-Filho, Otavio R.; Lemos, Pedro A. [Heart Institute (InCor), University of São Paulo Medical School (USP), São Paulo, SP (Brazil)

2015-04-15

The diagnostic accuracy of 64-slice MDCT in comparison with IVUS has been poorly described and is mainly restricted to reports analyzing segments with documented atherosclerotic plaques. We compared 64-slice multidetector computed tomography (MDCT) with gray scale intravascular ultrasound (IVUS) for the evaluation of coronary lumen dimensions in the context of a comprehensive analysis, including segments with absent or mild disease. The 64-slice MDCT was performed within 72 h before the IVUS imaging, which was obtained for at least one coronary, regardless of the presence of luminal stenosis at angiography. A total of 21 patients were included, with 70 imaged vessels (total length 114.6 ± 38.3 mm per patient). A coronary plaque was diagnosed in segments with plaque burden > 40%. At patient, vessel, and segment levels, average lumen area, minimal lumen area, and minimal lumen diameter were highly correlated between IVUS and 64-slice MDCT (p < 0.01). However, 64-slice MDCT tended to underestimate the lumen size with a relatively wide dispersion of the differences. The comparison between 64-slice MDCT and IVUS lumen measurements was not substantially affected by the presence or absence of an underlying plaque. In addition, 64-slice MDCT showed good global accuracy for the detection of IVUS parameters associated with flow-limiting lesions. In a comprehensive, multi-territory, and whole-artery analysis, the assessment of coronary lumen by 64-slice MDCT compared with coronary IVUS showed a good overall diagnostic ability, regardless of the presence or absence of underlying atherosclerotic plaques.

Characterization of atherosclerotic disease in thoracic aorta: A 3D, multicontrast vessel wall imaging study

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Zhou, Changwu [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China); Department of Radiology, The Second Clinical Medical College, Yangzhou University, Yangzhou (China); Qiao, Huiyu; He, Le [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China); Yuan, Chun [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China); Department of Radiology, University of Washington, Seattle, WA (United States); Chen, Huijun; Zhang, Qiang; Li, Rui [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China); Wang, Wei; Du, Fang [Department of Radiology, The Second Clinical Medical College, Yangzhou University, Yangzhou (China); Li, Cheng, E-mail: cjr.licheng@vip.163.com [Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing (China); Zhao, Xihai, E-mail: xihaizhao@tsinghua.edu.cn [Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University School of Medicine, Beijing (China)

2016-11-15

Purpose: To investigate the characteristics of plaque in the thoracic aorta using three dimensional multicontrast magnetic resonance imaging. Materials and methods: Elderly subjects (≥60 years) were recruited in this study. Thoracic aorta was imaged on a 3.0T MR scanner by acquiring multicontrast sequences. The plaque burden was evaluated by measuring lumen area, wall area, wall thickness, and normalized wall index. The presence or absence of plaque and intraplaque hemorrhage (IPH)/mural thrombus (MT) were identified. The characteristics of atherosclerosis among different thoracic aorta segments (AAO: ascending aorta; AOA: aortic arch, and DOA: descending aorta) were determined. Results: Of 66 recruited subjects (mean age 72.3 ± 6.2 years, 30 males), 55 (83.3%) had plaques in the thoracic aorta. The prevalence of plaque in AAO, AOA, and DAO was 5.4%, 72.7%, and 71.2%, respectively. In addition, 21.2% of subjects were found to have lesions with IPH/MT in the thoracic aorta. The prevalence of IPH/MT in segment of AAO, AOA and DAO was 0%, 13.6%, and 12.1%, respectively. The aortic wall showed the highest NWI in DAO (34.1% ± 4.8%), followed by AOA (31.2% ± 5%), and AAO (26.8% ± 3.3%) (p < 0.001). Conclusion: Three dimensional multicontrast MR imaging is capable of characterizing atherosclerotic plaques in the thoracic aorta. The findings of high prevalence of plaques and the presence of high risk plaques in the thoracic aorta suggest early screening for aortic vulnerable lesions in the elderly.

Characterization of atherosclerotic disease in thoracic aorta: A 3D, multicontrast vessel wall imaging study

International Nuclear Information System (INIS)

Zhou, Changwu; Qiao, Huiyu; He, Le; Yuan, Chun; Chen, Huijun; Zhang, Qiang; Li, Rui; Wang, Wei; Du, Fang; Li, Cheng; Zhao, Xihai

2016-01-01

Purpose: To investigate the characteristics of plaque in the thoracic aorta using three dimensional multicontrast magnetic resonance imaging. Materials and methods: Elderly subjects (≥60 years) were recruited in this study. Thoracic aorta was imaged on a 3.0T MR scanner by acquiring multicontrast sequences. The plaque burden was evaluated by measuring lumen area, wall area, wall thickness, and normalized wall index. The presence or absence of plaque and intraplaque hemorrhage (IPH)/mural thrombus (MT) were identified. The characteristics of atherosclerosis among different thoracic aorta segments (AAO: ascending aorta; AOA: aortic arch, and DOA: descending aorta) were determined. Results: Of 66 recruited subjects (mean age 72.3 ± 6.2 years, 30 males), 55 (83.3%) had plaques in the thoracic aorta. The prevalence of plaque in AAO, AOA, and DAO was 5.4%, 72.7%, and 71.2%, respectively. In addition, 21.2% of subjects were found to have lesions with IPH/MT in the thoracic aorta. The prevalence of IPH/MT in segment of AAO, AOA and DAO was 0%, 13.6%, and 12.1%, respectively. The aortic wall showed the highest NWI in DAO (34.1% ± 4.8%), followed by AOA (31.2% ± 5%), and AAO (26.8% ± 3.3%) (p < 0.001). Conclusion: Three dimensional multicontrast MR imaging is capable of characterizing atherosclerotic plaques in the thoracic aorta. The findings of high prevalence of plaques and the presence of high risk plaques in the thoracic aorta suggest early screening for aortic vulnerable lesions in the elderly.

Atherosclerotic plaque composition: analysis with multicolor CT and targeted gold nanoparticles

NARCIS (Netherlands)

Cormode, David P.; Roessl, Ewald; Thran, Axel; Skajaa, Torjus; Gordon, Ronald E.; Schlomka, Jens-Peter; Fuster, Valentin; Fisher, Edward A.; Mulder, Willem J. M.; Proksa, Roland; Fayad, Zahi A.

2010-01-01

To investigate the potential of spectral computed tomography (CT) (popularly referred to as multicolor CT), used in combination with a gold high-density lipoprotein nanoparticle contrast agent (Au-HDL), for characterization of macrophage burden, calcification, and stenosis of atherosclerotic

Enterprise stent for the treatment of symptomatic intracranial atherosclerotic stenosis: an initial experience of 44 patients.

Science.gov (United States)

Feng, Zhengzhe; Duan, Guoli; Zhang, Ping; Chen, Lei; Xu, Yi; Hong, Bo; Zhao, Wenyuan; Liu, Jianmin; Huang, Qinghai

2015-10-08

Wingspan stenting for the treatment of complex intracranial atherosclerotic stenosis (ICAS), i.e., that involving tortuous vascular pathways, long (>15 mm) lesions or arterial bifurcations, has a relatively high risk of complications. This retrospective study assessed the safety and efficacy of undersized balloon angioplasty followed by deployment of the more flexible Enterprise stent for the treatment of complex symptomatic ICAS. Forty-four patients on combined antiplatelet therapy and intensive risk factor management and a symptomatic 70-99% stenosis of a major intracranial artery in complex settings that was treated with balloon angioplasty and Enterprise stent deployment between July 2009 and August 2013 were enrolled. Primary outcome was occurrence of ischemic or hemorrhagic stroke or death within 30 days after intervention. Secondary outcomes included procedural success (defined as achievement of 50% in-stent restenosis after mean 22 months follow-up. In this retrospective, single-center experience, undersized balloon angioplasty followed by Enterprise stent deployment appears technically feasible with a relatively low rate of complications for the treatment of complex symptomatic ICAS. Prospective, multicenter, randomized controlled trials against optimal medical management are warranted.

Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery

NARCIS (Netherlands)

Pasterkamp, G.; Schoneveld, A. H.; Hijnen, D. J.; de Kleijn, D. P.; Teepen, H.; van der Wal, A. C.; Borst, C.

2000-01-01

Atherosclerotic luminal narrowing is determined by plaque mass and the mode of geometrical remodeling. Recently, we reported that the type of atherosclerotic remodeling is associated with the presence of histological markers for plaque vulnerability. Inflammation and matrix degrading proteases

Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques

NARCIS (Netherlands)

Queiroz, Karla C. S.; Bijlsma, Maarten F.; Tio, René A.; Zeebregts, Clark J.; Dunaeva, Marina; Ferreira, Carmen V.; Fuhler, Gwenny M.; Kuipers, Ernst J.; Alves, Maria M.; Rezaee, Farhad; Spek, C. Arnold; Peppelenbosch, Maikel P.

2012-01-01

The major cause for plaque instability in atherosclerotic disease is neoangiogenic revascularization, but the factors controlling this process remain only partly understood. Hedgehog (HH) is a morphogen with important functions in revascularization, but its function in human healthy vessel biology

Cohort study of predictive value of urinary albumin excretion for atherosclerotic vascular disease in patients with insulin dependent diabetes

DEFF Research Database (Denmark)

Deckert, T; Yokoyama, H; Mathiesen, E

1996-01-01

atherosclerotic vascular disease during follow up of 2457 person year. Elevated urinary albumin excretion was significantly predictive of atherosclerotic vascular disease (hazard ratio 1.06 (95% confidence interval 1.02 to 1.18) per 5 mg increase in 24 hour urinary albumin excretion, P = 0.002). Predictive effect...

Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding.

Science.gov (United States)

Maaninka, Katariina; Nguyen, Su Duy; Mäyränpää, Mikko I; Plihtari, Riia; Rajamäki, Kristiina; Lindsberg, Perttu J; Kovanen, Petri T; Öörni, Katariina

2018-04-13

Subendothelial interaction of LDL with extracellular matrix drives atherogenesis. This interaction can be strengthened by proteolytic modification of LDL. Mast cells (MCs) are present in atherosclerotic lesions, and upon activation, they degranulate and release a variety of neutral proteases. Here we studied the ability of MC proteases to cleave apoB-100 of LDL and affect the binding of LDL to proteoglycans. Mature human MCs were differentiated from human peripheral blood-derived CD34 + progenitors in vitro and activated with calcium ionophore to generate MC-conditioned medium. LDL was incubated in the MC-conditioned medium or with individual MC proteases, and the binding of native and modified LDL to isolated human aortic proteoglycans or to human atherosclerotic plaques ex vivo was determined. MC proteases in atherosclerotic human coronary artery lesions were detected by immunofluorescence and qPCR. Activated human MCs released the neutral proteases tryptase, chymase, carboxypeptidase A3, cathepsin G, and granzyme B. Of these, cathepsin G degraded most efficiently apoB-100, induced LDL fusion, and enhanced binding of LDL to isolated human aortic proteoglycans and human atherosclerotic lesions ex vivo. Double immunofluoresence staining of human atherosclerotic coronary arteries for tryptase and cathepsin G indicated that lesional MCs contain cathepsin G. In the lesions, expression of cathepsin G correlated with the expression of tryptase and chymase, but not with that of neutrophil proteinase 3. The present study suggests that cathepsin G in human atherosclerotic lesions is largely derived from MCs and that activated MCs may contribute to atherogenesis by enhancing LDL retention. Copyright © 2018 Elsevier B.V. All rights reserved.

An Algorithm for the Use of Embolic Protection During Atherectomy for Femoral Popliteal Lesions.

Science.gov (United States)

Krishnan, Prakash; Tarricone, Arthur; Purushothaman, K Raman; Purushothaman, Meerarani; Vasquez, Miguel; Kovacic, Jason; Baber, Usman; Kapur, Vishal; Gujja, Karthik; Kini, Annapoorna; Sharma, Samin

2017-02-27

This study sought to identify an algorithm for the use of distal embolic protection on the basis of angiographic lesion morphology and vascular anatomy for patients undergoing atherectomy for femoropopliteal lesions. Atherectomy has been shown to create more embolic debris than angioplasty alone. Distal embolic protection has been shown to be efficacious in capturing macroemboli; however, no consensus exists for the appropriate lesions to use distal embolic protection during atherectomy. Patients with symptomatic lower extremity peripheral artery disease treated with atherectomy and distal embolic protection were evaluated to identify potential predictors of DE. Plaque collected from the SilverHawk nose cone subset was sent to pathology for analysis to evaluate the accuracy of angiography in assessing plaque morphology. Significant differences were found in lesion length (142.1 ± 62.98 vs. 56.91 ± 41.04; p = 0.0001), low-density lipoprotein (82.3 ± 40.3 vs. 70.9 ± 23.2; p = 0.0006), vessel runoff (1.18 ± 0.9 vs. 1.8 ± 0.9; p = 0.0001), chronic total occlusion (131 vs. 10; p = 0.001), in-stent restenosis (33 vs. 6; p = 0.0081), and calcified lesions (136 vs. 65; p 40 mm, and atherosclerotic lesions >140 mm identified by peripheral angiography necessitate concomitant filter use during atherectomy to prevent embolic complications. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chlamydia in canine or feline coronary arteriosclerotic lesions

Directory of Open Access Journals (Sweden)

Grabarevic Zeljko

2011-09-01

Full Text Available Abstract Background There are numerous reports linking Chlamydia infection to human coronary atherosclerosis. However, there is a lack of data regarding this correlation in dogs and cats, and there are no reports investigating coronary arteriosclerosis and Chlamydia in these species. The aim of the present study was to examine whether there is a correlation between canine and feline spontaneous atherosclerosis or arteriosclerosis and the presence of Chlamydia. Archived histopathological samples of dogs (n = 16 and cats (n = 13 with findings of atherosclerosis or arteriosclerosis in heart tissue were examined for the presence of Chlamydiaceae using real-time PCR, ArrayTube Microarray and immunohistochemistry. Additionally, arteriosclerotic lesions of all cases were histologically classified and graded. Results Both canine atherosclerotic cases, and all 14 canine arteriosclerotic cases were negative for Chlamydia. Only one of the 13 arteriosclerotic feline cases was positive for Chlamydia by real-time PCR, revealing C. abortus by ArrayTube Microarray. To our knowledge, this is the first description of C. abortus in a cat. Overall, the type and grade of canine and feline arteriosclerotic lesions revealed similarities, and were predominantly moderate and hyperplastic. Conclusions These findings suggest that there is no obvious correlation between canine and feline coronary arteriosclerosis and the presence of Chlamydia. In order to draw final conclusions about the correlation between Chlamydia and canine atherosclerosis, examination of more samples is required.

Chlamydia in canine or feline coronary arteriosclerotic lesions.

Science.gov (United States)

Sostaric-Zuckermann, Ivan C; Borel, Nicole; Kaiser, Carmen; Grabarevic, Zeljko; Pospischil, Andreas

2011-09-09

There are numerous reports linking Chlamydia infection to human coronary atherosclerosis. However, there is a lack of data regarding this correlation in dogs and cats, and there are no reports investigating coronary arteriosclerosis and Chlamydia in these species. The aim of the present study was to examine whether there is a correlation between canine and feline spontaneous atherosclerosis or arteriosclerosis and the presence of Chlamydia. Archived histopathological samples of dogs (n = 16) and cats (n = 13) with findings of atherosclerosis or arteriosclerosis in heart tissue were examined for the presence of Chlamydiaceae using real-time PCR, ArrayTube Microarray and immunohistochemistry. Additionally, arteriosclerotic lesions of all cases were histologically classified and graded. Both canine atherosclerotic cases, and all 14 canine arteriosclerotic cases were negative for Chlamydia. Only one of the 13 arteriosclerotic feline cases was positive for Chlamydia by real-time PCR, revealing C. abortus by ArrayTube Microarray. To our knowledge, this is the first description of C. abortus in a cat. Overall, the type and grade of canine and feline arteriosclerotic lesions revealed similarities, and were predominantly moderate and hyperplastic. These findings suggest that there is no obvious correlation between canine and feline coronary arteriosclerosis and the presence of Chlamydia. In order to draw final conclusions about the correlation between Chlamydia and canine atherosclerosis, examination of more samples is required.

Interventional therapy of atherosclerotic renal artery occlusion

International Nuclear Information System (INIS)

Li Jian; Xu Ke; Xiao Liang

2009-01-01

Objective: To investigate the effectiveness of interventional therapy for the atherosclerotic renal artery occlusion (ARAO). Methods: During the period of June 2001-Dec. 2007, 16 patients with ARAO (total of 16 occluded arteries) underwent interventional managements, including percutaneous endovascular renal artery revascularization, balloon dilatation angioplasty and stent placement. Follow-up survey was made at regular intervals. The patent condition of the renal artery was evaluated with ultrasonography and digital subtraction angiography. The blood pressure and the renal function were determined and the data were statistically analyzed in order to assess the intermediate and long-term effect of the interventional therapy. Results: Of 16 patients, technical success was achieved in 15 (93.8%) and failure occurred in one. During a follow-up period of 9 - 24 months, 3 patients died. According to the data obtained at each patient's last follow-up survey, the hypertension fell to normal in 3 (25.0%), was improved in 7 (58.3%) and showed no marked change in 2 patients (16.7%), with a clinical efficacy of 83.3% (10 / 12). The renal function was improved in 2 (16.7%), stabilized in 6 (50%) and deteriorated in 4 patients (33.3%), with an effective rate of 66.7% (8 / 12). Conclusion: For the treatment of atherosclerotic renal artery occlusion, the interventional therapy carries high successful rate and can effectively lower the blood pressure level, in addition, it can also protect the renal function in a certain degree. (authors)

Cytomegalovirus localization in atherosclerotic plaques is associated with acute coronary syndromes: report of 105 patients.

Science.gov (United States)

Izadi, Morteza; Fazel, Mozhgan; Saadat, Seyed Hassan; Nasseri, Mohammad Hassan; Ghasemi, Mojtaba; Dabiri, Hossein; Aryan, Reza Safi; Esfahani, Ali Akbar; Ahmadi, Ali; Kazemi-Saleh, Davood; Kalantar-Motamed, Mohammad Hassan; Taheri, Saeed

2012-01-01

It has been shown that cytomegalovirus (CMV) is present in coronary atherosclerotic plaques, but the clinical relevance of this presence remains to be elucidated. In this study we sought to examine CMV infection in atherosclerosis patients defined by different methods and to identify the clinical significance of CMV replication in the atherosclerotic plaques. The study included 105 consecutive patients who were admitted to our department and underwent coronary artery bypass grafting (CABG) surgical interventions. Coronary atherosclerotic specimens as well as 53 specimens from the mamillary artery of these same patients were analyzed. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods were used for evaluations. The CMV PCR test result was positive for 28 (26.7%) of patients with coronary artery atherosclerosis. After adjusting for other risk factors, coronary artery disease patients with a history of acute coronary syndrome were more likely to be positive for CMV PCR test (P=0.027; odds ratio: 4.2; 95% CI: 1.18-15.0). They were also more likely to have a positive family history for cardiovascular diseases (CVD). This study confirms previous evidence about the replication of CMV virus in the atherosclerotic plaques of coronary arteries and brings clinical significance to this observation by showing a higher prevalence of acute coronary syndromes in those patients with CMV-infected plaques. Our study also suggests a familial vulnerability to CMV replication in the coronary artery walls.

A case of atherosclerotic inferior mesenteric artery aneurysm secondary to high flow state.

Science.gov (United States)

Troisi, Nicola; Esposito, Giovanni; Cefalì, Pietro; Setti, Marco

2011-07-01

Inferior mesenteric artery aneurysms are very rare and they are among the rarest of visceral artery aneurysms. Sometimes, the distribution of the blood flow due to chronic atherosclerotic occlusion of some arteries can establish an increased flow into a particular supplying district (high flow state). A high flow state in a stenotic inferior mesenteric artery in compensation for a mesenteric occlusive disease can produce a rare form of aneurysm. We report the case of an atherosclerotic inferior mesenteric aneurysm secondary to high flow state (association with occlusion of the celiac trunk and severe stenosis of the superior mesenteric artery), treated by open surgical approach. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Low-density lipoproteins cause atherosclerotic cardiovascular disease

DEFF Research Database (Denmark)

Ference, Brian A.; Ginsberg, Henry N.; Graham, Ian

2017-01-01

Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from...... proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects. Conclusion Consistent evidence from...

Akt2/LDLr double knockout mice display impaired glucose tolerance and develop more complex atherosclerotic plaques than LDLr knockout mice

NARCIS (Netherlands)

Rensing, Katrijn L.; de Jager, Saskia C. A.; Stroes, Erik S.; Vos, Mariska; Twickler, Marcel Th B.; Dallinga-Thie, Geesje M.; de Vries, Carlie J. M.; Kuiper, Johan; Bot, Ilze; von der Thüsen, Jan H.

2014-01-01

To characterize the phenotype of Akt2/low-density-lipoprotein receptor double knockout (dKO) (Akt2/LDLr dKO) mice with respect to insulin resistance and features of atherosclerotic plaque progression. Metabolic profile and atherosclerotic plaque progression were compared between LDLr KO mice and

Evaluation of atherosclerotic change of the aorta by enhanced computed tomography

International Nuclear Information System (INIS)

Takasu, Junichiro

1990-01-01

Intimal atherosclerotic changes of the aorta were quantified by enhanced computed tomography (enhanced CT) and were examined in terms of their relation to other atherosclerotic characteristics, including calcification and aortic pulse wave velocity, diameter of the aorta, and arteriosclerotic risk factors. A total of 413 subjects were studied, consisting of normal volunteers and patients with cardiovascular diseases. Enhanced CT revealed the atheromatous intima as a projecting and thickened wall. Thus, the ratio of the intimal atherosclerotic change to the whole round was determined in various aortic sites. The diameter of the aorta decreased in accordance with the location from the ascending aorta to aortic ending. The diameter of the infrarenal abdominal aorta was 1.5 times larger than that of the ascending aorta, irrespective of age. The diameter of each region of the aorta increased with advancing age; in the age group of 70 years or older, it was 1.5 times larger that that in the age group of 40 years or younger. The intimal change was noted in the middle descending thoracic aorta and infrarenal abdominal aorta. It was proportional to an increase in the aortic pulse wave velocity, the diameter of the aorta, and the intimal calcification. Intimal changes of the aorta were increased in cerebrovascular disease, ischemic heart disease, arteriosclerosis obliterans, hypertension and diabetes mellitus. In particular, hypertension accompanied by diabetes mellitus or high cholesterolemia tended to accelerate the intimal change. In conclusion, aortic intimal changes, as detected on enhanced CT, is useful for the noninvasive diagnosis of arteriosclerosis. (N.K.)

A specific 15-lipoxygenase inhibitor limits the progression and monocyte-macrophage enrichment of hypercholesterolemia-induced atherosclerosis in the rabbit.

Science.gov (United States)

Bocan, T M; Rosebury, W S; Mueller, S B; Kuchera, S; Welch, K; Daugherty, A; Cornicelli, J A

1998-02-01

Oxidant signalling and lipoprotein oxidation may play important roles in atherosclerotic lesion development. Given coincident localization of 15-lipoxygenase (15-LO), stereospecific products of 15-LO and epitopes of modified LDL in atherosclerotic lesions, we hypothesized that inhibition of 15-LO by PD146176, an inhibitor of 15-LO with an IC50 in cells or isolated enzyme of 0.5-0.8 microM, may limit atherosclerotic lesion development through regulation of monocyte-macrophage enrichment. Rabbits exposed to chronic endothelial denudation of the iliac-femoral artery were meal-fed a 0.25% cholesterol (C), 3% peanut oil (PNO), 3% coconut oil (CNO) diet twice daily with and without 175 mg/kg PD146176 for 12 weeks. In a second study, atherosclerotic lesions were pre-established in rabbits through chronic endothelial denudation and meal-fed a 0.5% C, 3% PNO, 3% CNO diet for 9 weeks and a 0% C/fat diet for 6 weeks prior to an 8 week administration of PD146176 at 175 mg/kg, q.d. Plasma total and lipoprotein cholesterol exposure were similar in control and PD146176-treated animals in both studies but PD146176 increased plasma triglyceride exposure 2- to 4-fold. Plasma PD146176 concentrations ranged from 99 to 214 ng/ml at 2 h post-dose. In the progression study, the iliac-femoral monocyte-macrophage area was reduced 71%, cross-sectional lesion area was unchanged and cholesteryl ester (CE) content was reduced 63%. In the regression study, size and macrophage content of iliac-femoral, fibrous plaque-like lesions were decreased 34%, CE content was reduced 19% and gross extent of thoracic aortic lesions were reduced 41%. We conclude that PD146176 can limit monocyte macrophage enrichment of atherosclerotic lesions and can attenuate development of fibrofoamy and fibrous plaque lesions in the absence of changes in plasma total or lipoprotein cholesterol concentrations.

Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques

Energy Technology Data Exchange (ETDEWEB)

Kuge, Yuji [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Takai, Nozomi; Ogawa, Yuki; Temma, Takashi; Nishigori, Kantaro; Ishino, Seigo; Kamihashi, Junko; Saji, Hideo [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Zhao, Yan [Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Kiyono, Yasushi [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); University of Fukui, Biomedical Imaging Research Center, Fukui (Japan); Shiomi, Masashi [Kobe University Graduate School of Medicine, Institute for Experimental Animals, Kobe (Japan)

2010-11-15

Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of {sup 99m}Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG{sub 3} and negative control IgG{sub 3} were radiolabelled with {sup 99m}Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield {sup 99m}Tc-MT1-MMP mAb and {sup 99m}Tc-IgG{sub 3}, respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed. {sup 99m}Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional {sup 99m}Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p < 0.0001), while {sup 99m}Tc-IgG{sub 3} accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest {sup 99m}Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 {+-} 1.9, %ID x BW/mm{sup 2} x 10{sup 2}), followed in decreasing order by fibroatheromatous (1.8 {+-} 1.3), collagen-rich (1.6 {+-} 1.0) and neointimal lesions (1.5 {+-} 1.5). In contrast, {sup 99m}Tc-IgG{sub 3} accumulation was almost independent of the histological grade of lesions. Higher {sup 99m}Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with {sup 99m}Tc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required. (orig.)

Intermittent hypoxia and hypercapnia induce pulmonary artery atherosclerosis and ventricular dysfunction in low density lipoprotein receptor deficient mice.

Science.gov (United States)

Douglas, Robert M; Bowden, Karen; Pattison, Jennifer; Peterson, Alexander B; Juliano, Joseph; Dalton, Nancy D; Gu, Yusu; Alvarez, Erika; Imamura, Toshihiro; Peterson, Kirk L; Witztum, Joseph L; Haddad, Gabriel G; Li, Andrew C

2013-12-01

Patients with obstructive sleep apnea, who experience episodic hypoxia and hypercapnia during sleep, often demonstrate increased inflammation, oxidative stress, and dyslipidemia. We hypothesized that sleep apnea patients would be predisposed to the development of atherosclerosis. To dissect the mechanisms involved, we developed an animal model in mice whereby we expose mice to intermittent hypoxia/hypercapnia (IHH) in normobaric environments. Two- to three-month-old low-density lipoprotein receptor deficient (Ldlr(-/-)) mice were fed a high-fat diet for 8 or 16 wk while being exposed to IHH for either 10 h/day or 24 h/day. Plasma lipid levels, pulmonary artery and aortic atherosclerotic lesions, and cardiac function were then assayed. Surprisingly, atherosclerosis in the aorta of IHH mice was similar compared with controls. However, in IHH mice, atherosclerosis was markedly increased in the trunk and proximal branches of the pulmonary artery of exposed mice; even though plasma cholesterol and triglycerides were lower than in controls. Hemodynamic analysis revealed that right ventricular maximum pressure and isovolumic relaxation constant were significantly increased in IHH exposed mice and left ventricular % fractional shortening was reduced. In conclusion, 1) Intermittent hypoxia/hypercapnia remarkably accelerated atherosclerotic lesions in the pulmonary artery of Ldlr(-/-) mice and 2) increased lesion formation in the pulmonary artery was associated with right and left ventricular dysfunction. These findings raise the possibility that patients with obstructive sleep apnea may be susceptible to atherosclerotic disease in the pulmonary vasculature, an observation that has not been previously recognized.

Comparison of Knoop and Vickers surface microhardness and transverse microradiography for the study of early caries lesion formation in human and bovine enamel.

Science.gov (United States)

Lippert, F; Lynch, R J M

2014-07-01

The aims of the present laboratory study were twofold: a) to investigate the suitability of Knoop and Vickers surface microhardness (SMH) in comparison to transverse microradiography (TMR) to investigate early enamel caries lesion formation; b) to compare the kinetics of caries lesion initiation and progression between human and bovine enamel. Specimens (90×bovine and 90×human enamel) were divided into six groups (demineralization times of 8/16/24/32/40/48h) of 15 per enamel type and demineralized using a partially saturated lactic acid solution. SMH was measured before and after demineralization and changes in indentation length (ΔIL) calculated. Lesions were characterized using TMR. Data were analyzed (two-way ANOVA) and Pearson correlation coefficients calculated. ΔIL increased with increasing demineralization times but plateaued after 40h, whereas lesion depth (L) and integrated mineral loss (ΔZ) increased almost linearly throughout. No differences between Knoop and Vickers SMH in their ability to measure enamel demineralization were observed as both correlated strongly. Overall, ΔIL correlated strongly with ΔZ and L but only moderately with the degree of surface zone mineralization, whereas ΔZ and L correlated strongly. Bovine demineralized faster than human enamel (all techniques). Lesions in bovine formed faster than in human enamel, although the resulting lesions were almost indistinguishable in their mineral distribution characteristics. Early caries lesion demineralization can be sufficiently studied by SMH, but its limitations on the assessment of the mineral status of more demineralized lesions must be considered. Ideally, complementary techniques to assess changes in both physical and chemical lesion characteristics would be employed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral vascular disease.

LENUS (Irish Health Repository)

Saeed, A

2012-01-31

Atherosclerotic peripheral vascular disease is a common presenting cause for digital ischaemia in life long smokers. Acute severe Type II Cryoglobulinaemic vasculitis is a rare yet important cause, which may present with similar clinical features and which if undiagnosed may be rapidly fatal. Following the instigation of therapy with intravenous methylprednisolone and cyclophosphamide this patient made an excellent recovery.

Anatomical and Physiological Changes after Paclitaxel-Coated Balloon for Atherosclerotic De Novo Coronary Lesions: Serial IVUS-VH and FFR Study.

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Soe Hee Ann

Full Text Available To assess the serial changes of de novo coronary lesions treated with paclitaxel-coated balloon (PCB using intravascular ultrasound virtual histology (IVUS-VH and fractional flow reserve (FFR.This prospective observational study enrolled 27 patients with coronary artery disease treated with PCB who underwent coronary angiography, IVUS-VH and FFR before, immediately after intervention and at 9 months. 28 de novo lesions were successfully treated with PCB. Angiographic late luminal loss was 0.02 ± 0.27 mm. Mean vessel and lumen areas showed increase at 9 months (12.0 ± 3.5 mm(2 to 13.2 ± 3.9 mm(2, p <0.001; and 5.4 ± 1.2 mm(2 to 6.5 ± 1.8 mm(2, p <0.001, respectively. Although mean plaque area was unchanged (6.6 ± 2.6 mm2 to 6.6 ± 2.4 mm(2, p = 0.269, percent atheroma volume decreased significantly (53.4 ± 7.9% to 49.5 ± 6.4%, p = 0.002. The proportion of plaque compositions including fibrous, fibrofatty, dense calcium and necrotic core by IVUS-VH was unchanged at 9 months. The FFR of the treated lesion was 0.71 ± 0.13 pre-procedure, 0.87 ± 0.06 post-procedure and 0.84 ± 0.06 at follow-up.De novo coronary lesions treated with PCB showed persistent anatomical and physiological patency with plaque redistribution and vessel remodeling without chronic elastic recoil or plaque compositional change during follow-up.

Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

DEFF Research Database (Denmark)

Barascuk, Natasha; Skjøt-Arkil, Helene; Register, Thomas C

2010-01-01

BACKGROUND: Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular...... matrix (ECM) of atherosclerotic plaques by cathepsin K mediated processes. METHODS: We 1) cultured human macrophages on ECM and measured cathepsin K generated fragments of type I collagen (C-terminal fragments of Type I collagen (CTX-I) 2) investigated the presence of CTX-I in human coronary arteries......-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women...

Rupture of the atherosclerotic plaque: does a good animal model exist?

NARCIS (Netherlands)

Cullen, Paul; Baetta, Roberta; Bellosta, Stefano; Bernini, Franco; Chinetti, Giulia; Cignarella, Andrea; von Eckardstein, Arnold; Exley, Andrew; Goddard, Martin; Hofker, Marten; Hurt-Camejo, Eva; Kanters, Edwin; Kovanen, Petri; Lorkowski, Stefan; McPheat, William; Pentikäinen, Markku; Rauterberg, Jürgen; Ritchie, Andrew; Staels, Bart; Weitkamp, Benedikt; de Winther, Menno

2003-01-01

By its very nature, rupture of the atherosclerotic plaque is difficult to study directly in humans. A good animal model would help us not only to understand how rupture occurs but also to design and test treatments to prevent it from happening. However, several difficulties surround existing models

Oxidative Stress in Cardiovascular Diseases: Involvement of Nrf2 Antioxidant Redox Signaling in Macrophage Foam Cells Formation

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Bee Kee Ooi

2017-11-01

Full Text Available Oxidative stress is an important risk factor contributing to the pathogenesis of cardiovascular diseases. Oxidative stress that results from excessive reactive oxygen species (ROS production accounts for impaired endothelial function, a process which promotes atherosclerotic lesion or fatty streaks formation (foam cells. Nuclear factor erythroid 2-related factor 2 (Nrf2 is a transcription factor involved in cellular redox homeostasis. Upon exposure to oxidative stress, Nrf2 is dissociated from its inhibitor Keap-1 and translocated into the nucleus, where it results in the transcriptional activation of cell defense genes. Nrf2 has been demonstrated to be involved in the protection against foam cells formation by regulating the expression of antioxidant proteins (HO-1, Prxs, and GPx1, ATP-binding cassette (ABC efflux transporters (ABCA1 and ABCG1 and scavenger receptors (scavenger receptor class B (CD36, scavenger receptor class A (SR-A and lectin-type oxidized LDL receptor (LOX-1. However, Nrf2 has also been reported to exhibit pro-atherogenic effects. A better understanding on the mechanism of Nrf2 in oxidative stress-induced cardiac injury, as well as the regulation of cholesterol uptake and efflux, are required before it can serve as a novel therapeutic target for cardiovascular diseases prevention and treatment.

In vivo inhibition of nuclear factor of activated T-cells leads to atherosclerotic plaque regression in IGF-II/LDLR-/-ApoB100/100 mice.

Science.gov (United States)

Blanco, Fabiana; Heinonen, Suvi E; Gurzeler, Erika; Berglund, Lisa M; Dutius Andersson, Anna-Maria; Kotova, Olga; Jönsson-Rylander, Ann-Cathrine; Ylä-Herttuala, Seppo; Gomez, Maria F

2018-03-01

Despite vast clinical experience linking diabetes and atherosclerosis, the molecular mechanisms leading to accelerated vascular damage are still unclear. Here, we investigated the effects of nuclear factor of activated T-cells inhibition on plaque burden in a novel mouse model of type 2 diabetes that better replicates human disease. IGF-II/LDLR -/- ApoB 100/100 mice were generated by crossbreeding low-density lipoprotein receptor-deficient mice that synthesize only apolipoprotein B100 (LDLR -/- ApoB 100/100 ) with transgenic mice overexpressing insulin-like growth factor-II in pancreatic β cells. Mice have mild hyperglycaemia and hyperinsulinaemia and develop complex atherosclerotic lesions. In vivo treatment with the nuclear factor of activated T-cells blocker A-285222 for 4 weeks reduced atherosclerotic plaque area and degree of stenosis in the brachiocephalic artery of IGF-II/LDLR -/- ApoB 100/100 mice, as assessed non-invasively using ultrasound biomicroscopy prior and after treatment, and histologically after termination. Treatment had no impact on plaque composition (i.e. muscle, collagen, macrophages). The reduced plaque area could not be explained by effects of A-285222 on plasma glucose, insulin or lipids. Inhibition of nuclear factor of activated T-cells was associated with increased expression of atheroprotective NOX4 and of the anti-oxidant enzyme catalase in aortic vascular smooth muscle cells. Targeting the nuclear factor of activated T-cells signalling pathway may be an attractive approach for the treatment of diabetic macrovascular complications.

Phase-based vascular input function: Improved quantitative DCE-MRI of atherosclerotic plaques

NARCIS (Netherlands)

van Hoof, R. H. M.; Hermeling, E.; Truijman, M. T. B.; van Oostenbrugge, R. J.; Daemen, J. W. H.; van der Geest, R. J.; van Orshoven, N. P.; Schreuder, A. H.; Backes, W. H.; Daemen, M. J. A. P.; Wildberger, J. E.; Kooi, M. E.

2015-01-01

Purpose: Quantitative pharmacokinetic modeling of dynamic contrast-enhanced (DCE)-MRI can be used to assess atherosclerotic plaque microvasculature, which is an important marker of plaque vulnerability. Purpose of the present study was (1) to compare magnitude-versus phase-based vascular input

Spectral CT of carotid atherosclerotic plaque: comparison with histology

Energy Technology Data Exchange (ETDEWEB)

Zainon, R.; Doesburg, R.M. [University of Canterbury, Department of Physics and Astronomy, Christchurch (New Zealand); Ronaldson, J.P.; Gieseg, S.P. [University of Otago, Centre for Bioengineering, Christchurch (New Zealand); Janmale, T. [University of Canterbury, Free Radical Biochemistry Laboratory, School of Biological Sciences, Christchurch (New Zealand); Scott, N.J. [University of Otago, Department of Medicine, Christchurch (New Zealand); Buckenham, T.M. [University of Otago, Department of Academic Radiology, Christchurch (New Zealand); Butler, A.P.H. [University of Otago, Centre for Bioengineering, Christchurch (New Zealand); University of Otago, Department of Academic Radiology, Christchurch (New Zealand); University of Canterbury, Department of Electrical and Computer Engineering, Christchurch (New Zealand); European Organisation for Nuclear Research (CERN), Geneva (Switzerland); Butler, P.H. [University of Canterbury, Department of Physics and Astronomy, Christchurch (New Zealand); European Organisation for Nuclear Research (CERN), Geneva (Switzerland); Roake, J.A. [Christchurch Hospital, Department of Vascular, Endovascular and Transplant Surgery, Christchurch (New Zealand); Anderson, N.G. [University of Otago, Centre for Bioengineering, Christchurch (New Zealand); University of Otago, Department of Academic Radiology, Christchurch (New Zealand); University of Otago, Christchurch, Department of Radiology, PO Box 4345, Christchurch (New Zealand)

2012-12-15

To distinguish components of vulnerable atherosclerotic plaque by imaging their energy response using spectral CT and comparing images with histology. After spectroscopic calibration using phantoms of plaque surrogates, excised human carotid atherosclerotic plaques were imaged using MARS CT using a photon-processing detector with a silicon sensor layer and microfocus X-ray tube (50 kVp, 0.5 mA) at 38-{mu}m voxel size. The plaques were imaged, sectioned and re-imaged using four threshold energies: 10, 16, 22 and 28 keV; then sequentially stained with modified Von Kossa, Perl's Prussian blue and Oil-Red O, and photographed. Relative Hounsfield units across the energies were entered into a linear algebraic material decomposition model to identify the unknown plaque components. Lipid, calcium, iron and water-like components of plaque have distinguishable energy responses to X-ray, visible on spectral CT images. CT images of the plaque surface correlated very well with histological photographs. Calcium deposits (>1,000 {mu}m) in plaque are larger than iron deposits (<100 {mu}m), but could not be distinguished from each other within the same voxel using the energy range available. Spectral CT displays energy information in image form at high spatial resolution, enhancing the intrinsic contrast of lipid, calcium and iron within atheroma. (orig.)

A rabbit model of atherosclerosis at carotid artery: MRI visualization and histopathological characterization

International Nuclear Information System (INIS)

Ma, Zhan-Long; Teng, Gao-Jun; Chen, Jun; Zhang, Hong-Ying; Cao, Ai-Hong; Ni, Yicheng

2008-01-01

To induce a rabbit model of atherosclerosis at carotid artery, to visualize the lesion evolution with magnetic resonance imaging (MRI), and to characterize the lesion types by histopathology. Atherosclerosis at the right common carotid artery (RCCA) was induced in 23 rabbits by high-lipid diet following balloon catheter injury to the endothelium. The rabbits were examined in vivo with a 1.5-T MRI and randomly divided into three groups of 6 weeks (n=6), 12 weeks (n=8) and 15 weeks (n=9) for postmortem histopathology. The lesions on both MRI and histology were categorized according to the American Heart Association (AHA) classifications of atherosclerosis. Type I and type II of atherosclerotic changes were detected at week 6, i.e., nearly normal signal intensity (SI) of the injured RCCA wall without stenosis on MRI, but with subendothelial inflammatory infiltration and proliferation of smooth muscle cells on histopathology. At week 12, 75.0% and 62.5% of type III changes were encountered on MRI and histopathology respectively with thicker injured RCCA wall of increased SI on T 1 -weighted and proton density (PD)-weighted MRI and microscopically a higher degree of plaque formation. At week 15, carotid atherosclerosis became more advanced, i.e., type IV and type V in 55.6% and 22.2% of the lesions with MRI and 55.6% and 33.3% of the lesions with histopathology, respectively. Statistical analysis revealed a significant agreement (p<0.05) between the MRI and histological findings for lesion classification (r=0.96). A rabbit model of carotid artery atherosclerosis has been successfully induced and noninvasively visualized. The atherosclerotic plaque formation evolved from type I to type V with time, which could be monitored with 1.5-T MRI and confirmed with histomorphology. This experimental setting can be applied in preclinical research on atherosclerosis. (orig.)

Review of osteoimmunology and the host response in endodontic and periodontal lesions

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Dana T. Graves

2011-01-01

Full Text Available Both lesions of endodontic origin and periodontal diseases involve the host response to bacteria and the formation of osteolytic lesions. Important for both is the upregulation of inflammatory cytokines that initiate and sustain the inflammatory response. Also important are chemokines that induce recruitment of leukocyte subsets and bone-resorptive factors that are largely produced by recruited inflammatory cells. However, there are differences also. Lesions of endodontic origin pose a particular challenge since that bacteria persist in a protected reservoir that is not readily accessible to the immune defenses. Thus, experiments in which the host response is inhibited in endodontic lesions tend to aggravate the formation of osteolytic lesions. In contrast, bacteria that invade the periodontium appear to be less problematic so that blocking arms of the host response tend to reduce the disease process. Interestingly, both lesions of endodontic origin and periodontitis exhibit inflammation that appears to inhibit bone formation. In periodontitis, the spatial location of the inflammation is likely to be important so that a host response that is restricted to a subepithelial space is associated with gingivitis, while a host response closer to bone is linked to bone resorption and periodontitis. However, the persistence of inflammation is also thought to be important in periodontitis since inflammation present during coupled bone formation may limit the capacity to repair the resorbed bone.

Phenotypic modulation of smooth muscle cells during formation of neointimal thickenings following vascular injury.

Science.gov (United States)

Thyberg, J

1998-07-01

Smooth muscle cells build up the media of mammalian arteries and constitute one of the principal cell types in atherosclerotic and restenotic lesions. Accordingly, they show a high degree of plasticity and are able to shift from a differentiated, contractile phenotype to a less differentiated, synthetic phenotype, and then back again. This modulation occurs as a response to vascular injury and includes a prominent structural reorganization with loss of myofilaments and formation of an extensive endoplasmic reticulum and a large Golgi complex. At the same time, the expression of cytoskeletal proteins and other gene products is altered. As a result, the cells lose their contractility and become able to migrate from the media to the intima, proliferate, and secrete extracellular matrix components, thereby contributing to the formation of intimal thickenings. The mechanisms behind this change in morphology and function of the smooth muscle cells are still incompletely understood. A crucial role has been ascribed to basement membrane proteins such as laminin and collagen type IV and adhesive proteins such as fibronectin. A significant role is also played by mitogenic proteins such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF). An improved knowledge of the regulation of smooth muscle differentiated properties represents an important part in the search for new methods of prevention and treatment of vascular disease.

Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques

DEFF Research Database (Denmark)

Fumagalli, Stefano; Perego, Carlo; Zangari, Rosalia

2017-01-01

Inflammatory mechanisms may be involved in atherosclerotic plaque rupture. By using a novel histology-based method to quantify plaque instability here, we assess whether lectin pathway (LP) of complement activation, a major inflammation arm, could represent an index of plaque instability. Plaques...

Cognitive functioning and quality of life of atherosclerotic patients following carotid endarterectomy.

NARCIS (Netherlands)

Bossema, E.R.; Brand, A.N.; Moll, F.L.; Ackerstaff, R.G.A.; Doornen, L.J.P. van

2002-01-01

Background: Carotid endarterectomy (CEA) is a surgical procedure to remove atherosclerotic plaque from one of the carotid arteries in patients with severe stenosis. The purpose is to prevent future cerebral ischemic attacks. Whether patients, in addition, improve in cognitive functions and quality

A water-soluble extract of chicken reduced plasma triacylglycerols, but showed no anti-atherosclerotic activity in apoE−/− mice

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Rita Vik

2015-08-01

Conclusion: Chicken protein displayed a slight potential to increase mitochondrial fatty acid oxidation and reduce plasma TAG. However, CP did not affect plasma cholesterol levels, inflammation status or atherosclerotic development in apoE−/− mice. Based on these results, dietary intervention with CP does not have sufficient capacity to influence atherosclerotic development in apoE−/− mice.

Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

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Long Wang

2018-01-01

Full Text Available Objective: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. Methods: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP. At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. Results: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05. Conclusion: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. Keywords: blood fat, blood glucose, blood pressure, coronary sclerosis, heart disease

IGF-1, oxidative stress, and atheroprotection

Science.gov (United States)

Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung; Delafontaine, Patrice

2009-01-01

Atherosclerosis is a chronic inflammatory disease in which early endothelial dysfunction and subintimal modified lipoprotein deposition progress to complex, advanced lesions that are predisposed to erosion, rupture and thrombosis. Oxidative stress plays a critical role not only in initial lesion formation but also in lesion progression and destabilization. While growth factors are thought to promote vascular smooth muscle cell proliferation and migration, thereby increasing neointima, recent animal studies indicate that IGF-1 exerts pleiotropic anti-oxidant effects along with anti-inflammatory effects that together reduce atherosclerotic burden. This review discusses the effects of IGF-1 in vascular injury and atherosclerosis models, emphasizing the relationship between oxidative stress and potential atheroprotective actions of IGF-1. PMID:20071192

Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

International Nuclear Information System (INIS)

Liu, Chun; Ge, Beihai; He, Chao; Zhang, Yi; Liu, Xiaowen; Liu, Kejian; Qian, Cuiping; Zhang, Yu; Peng, Wenzhong; Guo, Xiaomei

2014-01-01

Highlights: • Mfn2 decreases cellular lipid accumulation by activating cholesterol transporters. • PPARγ is involved in the Mfn2-mediated increase of cholesterol transporter expressions. • Inactivation of ERK1/2 and p38 is involved in Mfn2-induced PPARγ expression. - Abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease

Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

Energy Technology Data Exchange (ETDEWEB)

Liu, Chun; Ge, Beihai [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); He, Chao [Department of Cardiology, China Three Gorges University, Yichang 433000 (China); Zhang, Yi; Liu, Xiaowen [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); Liu, Kejian [Department of Cardiology, The First Affiliated Hospital of Medical College, Shihezi University (China); Qian, Cuiping; Zhang, Yu; Peng, Wenzhong [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); Guo, Xiaomei, E-mail: xmguo@tjh.tjmu.edu.cn [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China)

2014-07-18

Highlights: • Mfn2 decreases cellular lipid accumulation by activating cholesterol transporters. • PPARγ is involved in the Mfn2-mediated increase of cholesterol transporter expressions. • Inactivation of ERK1/2 and p38 is involved in Mfn2-induced PPARγ expression. - Abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease.

DNA adducts and human atherosclerotic lesions

Czech Academy of Sciences Publication Activity Database

Binková, Blanka; Strejc, P.; Boubelík, O.; Stávková, Zdena; Chvátalová, Irena; Šrám, Radim

2001-01-01

Roč. 204, - (2001), s. 49-54 ISSN 1438-4639 R&D Projects: GA MŽP SI/340/00 Institutional research plan: CEZ:AV0Z5039906 Keywords : atherosclerosis * autopsy thoracic aortas Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 0.480, year: 2001

Nuclear medicine and coronary artery disease: evaluation of tracers of myocardial perfusion and vulnerable atherosclerotic plaque

International Nuclear Information System (INIS)

Broisat, A.

2005-04-01

Coronary artery disease is one of the primary cause of mortality worldwide. Nuclear medicine is the major imaging technique for diagnosis and following of this disease. perfusion: nowadays, major radioactive agents used in clinical practice are myocardial perfusion tracers. The reference tracer is thallium-201. However, 201 Tl presents some drawbacks. 99m Tcn-noet has been proposed for its replacement. This study shows that in contrast with previous studies realized in vitro on cardio myocytes, verapamil, an l-type calcium channel inhibitor, does not inhibit myocardial fixation of 99m Tcn-noet in vivo in dog. This data is in agreement with the hypothesis of a non specific endothelial fixation of this tracer. Moreover, this study shows that as a pure tracer of myocardial perfusion, 99m Tcn-noet can also be used to assess myocardial viability on a model of myocardial chronic infarction in rat. atherosclerosis: disruption of vulnerable atherosclerotic plaques is the main event leading to coronary accidents. The second part of this study concerns the evaluation of new potential tracers of the vulnerable atherosclerotic plaque in an experimental model of rabbit with an inheritable hypercholesterolemia. The four tracers evaluated (b2702(r), b2702-I, b2702-Tc and Tc-raft-b2702) are synthetic peptides comprising the residues 75-84 of hla-b2702, a molecule known to link vcam-1, an adhesion molecule expressed in vulnerable atherosclerotic plaque. The autoradiography studies show that all tracers accumulate within atherosclerotic plaque expressing vcam- and that. i-b2702 shows the best plaque/control fixation ratio. (author)

Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay Formation is Essential for Functional Regeneration

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Anne Tscherter

2016-09-01

Full Text Available Presently there exists no cure for spinal cord injury. However, transplantation of embryonic tissue into spinal cord lesions resulted in axon outgrowth across the lesion site and some functional recovery, fostering hope for future stem cell therapies. Although in vivo evidence for functional recovery is given, the exact cellular mechanism of the graft support remains elusive: either the grafted cells provide a permissive environment for the host tissue to regenerate itself or the grafts actually integrate functionally into the host neuronal network reconnecting the separated spinal cord circuits. We tested the two hypotheses in an in vitro spinal cord lesion model that is based on propagation of activity between two rat organotypic spinal cord slices in culture. Transplantation of dissociated cells from E14 rat spinal cord or forebrain re-established the relay of activity over the lesion site and, thus, provoked functional regeneration. Combining patch-clamp recordings from transplanted cells with network activity measurements from the host tissue on multi-electrode arrays we here show that neurons differentiate from the grafted cells and integrate into the host circuits. Optogenetic silencing of neurons developed from transplanted embryonic mouse forebrain cells provides clear evidence that they replace the lost neuronal connections to relay and synchronize activity between the separated spinal cord circuits. In contrast, transplantation of neurospheres induced neither the differentiation of mature neurons from the grafts nor an improvement of functional regeneration. Together these findings suggest, that the formation of neuronal relays from grafted embryonic cells is essential to re-connect segregated spinal cord circuits.

Evaluation of early atherosclerotic findings in women with polycystic ovary syndrome

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Mohammadi Afshin

2011-10-01

Full Text Available Background Polycystic ovary syndrome (PCOS is the most common endocrinopathy in women of childbearing age, and it seems better to consider it as an ovarian manifestation of metabolic syndrome. The aim of the current study was to evaluate early atherosclerotic findings in patients with PCOS. Methods We enrolled 46 women with PCOS and 45 normal control subjects who were referred to our hospital's endocrinology outpatient clinic. Carotid intima media thickness (CIMT and flow-mediated dilatation (FMD were performed in both cases and matched controls. Results Patients with PCOS showed an increased mean CIMT (0.63 ± 0.16 mm when compared with the control subjects (0.33 ± 0.06 mm. This difference was statistically significant (p = 0.001. The mean FMD in young patients with PCOS was 10.07 ± 1.2%, while it was 6.5 ± 2.06% in normal subjects. This difference was also statistically significant (p = 0.001. Conclusion Our findings suggest that PCOS is related with early atherosclerotic findings.

Distribution of ultraviolet-induced lesions in Simian Virus 40 DNA

International Nuclear Information System (INIS)

Bourre, F.; Renault, G.; Sarasin, A.; Seawell, P.C.

1985-01-01

In order to analyze the molecular mechanisms of mutagenesis in mammalian cells, we devised an analytical assay using Simian Virus 40 as biological probe. To study the possible correlations between the distribution of the lesions on the treated DNA and the distribution of mutations, we have located and quantified the lesions induced by ultraviolet light (254 nm) on a SV40 DNA fragment. At a fluence of 2,000J/m 2 , our results show that the formation frequency of thymine-thymine dimers (TT) is three to four times higher than the formation frequency of the other types of dimers (TC, CT, CC). On the other hand, the formation frequency of a dimer is influenced by the adjacent sequence. In particular, a pyrimidine in the 5' position of a thymine-thymine dimer enhances its formation frequency. At the dose used the formation frequency of the pyrimidine (6-4) pyrimidone photoproducts is twenty times less than the formation frequency of pyrimidine dimers. This paper shows the distribution of the major lesions induced by UV-light on a defined fragment of SV40 genome after UV irradiation. This work is necessary to get an insight in the molecular mechanisms of UV-mutagenesis

Penetrating atherosclerotic ulcer of the aorta: A continuing debate

International Nuclear Information System (INIS)

Patatas, K.; Shrivastava, V.; Ettles, D.F.

2013-01-01

Aortic penetrating atherosclerotic ulcer (PAU) is a relatively common incidental finding on thoracic computed tomography (CT) examinations. This is likely to relate to the steady increase in the number of CT examinations performed and also due, in part, to the increasing age of the general population. There is as yet no consensus on the management of incidental PAUs in asymptomatic patients. This article aims to review the literature and discuss the natural history, prognosis, and management of incidental PAU

4-Hydroxynonenal Contributes to Angiogenesis through a Redox-Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives

Directory of Open Access Journals (Sweden)

Caroline Camaré

2017-01-01

Full Text Available The neovascularization of atherosclerotic lesions is involved in plaque development and may contribute to intraplaque hemorrhage and plaque fragilization and rupture. Among the various proangiogenic agents involved in the neovascularization process, proatherogenic oxidized LDLs (oxLDLs contribute to the formation of tubes via the generation of sphingosine 1-phosphate (S1P, a major mitogenic and proangiogenic sphingolipid mediator. In this study, we investigated whether 4-hydroxynonenal (4-HNE, an aldehydic lipid oxidation product abundantly present in oxLDLs, contributes to their proangiogenic properties. Immunofluorescence analysis of human atherosclerotic lesions from carotid endarterectomy showed the colocalization of HNE-adducts with CD31, a marker of endothelial cells, suggesting a close relationship between 4-HNE and neovessel formation. In vitro, low 4-HNE concentration (0.5–1 µM elicited the formation of tubes by human microvascular endothelial cells (HMEC-1, whereas higher concentrations were not angiogenic. The formation of tubes by 4-HNE involved the generation of reactive oxygen species and the activation of the sphingolipid pathway, namely, the neutral type 2 sphingomyelinase and sphingosine kinase-1 (nSMase2/SK-1 pathway, indicating a role for S1P in the angiogenic signaling of 4-HNE. Carbonyl scavengers hydralazine and bisvanillyl-hydralazone inhibited the nSMase2/SK1 pathway activation and the formation of tubes on Matrigel® evoked by 4-HNE. Altogether, these results emphasize the role of 4-HNE in the angiogenic effect of oxLDLs and point out the potential interest of pharmacological carbonyl scavengers to prevent the neovascularization process.

Chronic atherosclerotic mesenteric ischemia that started to develop symptoms just after anaphylaxis.

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Goto, M; Matsuzaki, M; Fuchinoue, A; Urabe, N; Kawagoe, N; Takemoto, I; Tanaka, H; Watanabe, T; Miyazaki, T; Takeuchi, M; Honda, Y; Nakanishi, K; Urita, Y; Shimada, N; Nakajima, H; Sugimoto, M; Goto, T

2012-05-01

An 83-year-old woman was referred to our emergency department with acute urticaria and sudden shortness of breath approximately 30 min after taking rectal diclofenac potassium for lumbago. After treatment with adrenaline and corticosteroids, the patient became hemodynamically stable and left the hospital on the next day. She attended our hospital 1 week after the onset of anaphylaxis because of repeated postprandial epigastric pain. No abnormal lesions were found in endoscopy. Radiographic selective catheter angiography revealed chronic mesenteric ischemia caused by atherosclerosis and abundant collateral arteries between the celiac trunk, the superior mesenteric artery and the inferior mesenteric artery. Patients with chronic mesenteric ischemia usually present with a clinical syndrome characterized by painful abdominal cramps and colic occurring typically during the postprandial phase. Fear of eating resulted in malnutrition. She was prescribed proton pump inhibitor, digestants, anticholinergic agents, serine protease inhibitors, prokinetics, antiplatelet agents and transdermal nitroglycerin intermittently, but these had no beneficial effects. It was most probable that this patient with chronic atherosclerotic mesenteric ischemia was suffering from functional abdominal pain syndrome induced by anaphylaxis. Since psychiatric disorders were associated with alterations in the processing of visceral sensation, we facilitated the patient's understanding of functional abdominal pain syndrome with the psychologist. Postprandial abdominal pain gradually faded after administration of these drugs and the patient left the hospital. Developing a satisfactory patient-physician relationship was considered more effective for the management of persistent abdominal pain caused by complicated mechanisms.

Chronic Atherosclerotic Mesenteric Ischemia That Started to Develop Symptoms Just after Anaphylaxis

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M. Goto

2012-05-01

Full Text Available An 83-year-old woman was referred to our emergency department with acute urticaria and sudden shortness of breath approximately 30 min after taking rectal diclofenac potassium for lumbago. After treatment with adrenaline and corticosteroids, the patient became hemodynamically stable and left the hospital on the next day. She attended our hospital 1 week after the onset of anaphylaxis because of repeated postprandial epigastric pain. No abnormal lesions were found in endoscopy. Radiographic selective catheter angiography revealed chronic mesenteric ischemia caused by atherosclerosis and abundant collateral arteries between the celiac trunk, the superior mesenteric artery and the inferior mesenteric artery. Patients with chronic mesenteric ischemia usually present with a clinical syndrome characterized by painful abdominal cramps and colic occurring typically during the postprandial phase. Fear of eating resulted in malnutrition. She was prescribed proton pump inhibitor, digestants, anticholinergic agents, serine protease inhibitors, prokinetics, antiplatelet agents and transdermal nitroglycerin intermittently, but these had no beneficial effects. It was most probable that this patient with chronic atherosclerotic mesenteric ischemia was suffering from functional abdominal pain syndrome induced by anaphylaxis. Since psychiatric disorders were associated with alterations in the processing of visceral sensation, we facilitated the patient’s understanding of functional abdominal pain syndrome with the psychologist. Postprandial abdominal pain gradually faded after administration of these drugs and the patient left the hospital. Developing a satisfactory patient-physician relationship was considered more effective for the management of persistent abdominal pain caused by complicated mechanisms.

Nanomedicine for the prevention, treatment and imaging of atherosclerosis.

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Psarros, Costas; Lee, Regent; Margaritis, Marios; Antoniades, Charalambos

2012-09-01

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in developed countries, with an increasing prevalence due to an aging population. The pathology underpinning CVD is atherosclerosis, a chronic inflammatory state involving the arterial wall. Accumulation of low density lipoprotein (LDL) laden macrophages in the arterial wall and their subsequent transformation into foam cells lead to atherosclerotic plaque formation. Progression of atherosclerotic lesions may gradually lead to plaque related complications and clinically manifest as acute vascular syndromes including acute myocardial or cerebral ischemia. Nanotechnology offers emerging therapeutic strategies, which may have advantage overclassical treatments for atherosclerosis. In this review, we present the potential applications of nanotechnology toward prevention, identification and treatment of atherosclerosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

NARCIS (Netherlands)

Bot, M.; , van, Berkel T.J.C.

2013-01-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by

Renal function during pregnancy may predict risk of future hospitalization due to atherosclerotic-related morbidity.

Science.gov (United States)

Wolak, Talya; Shoham-Vardi, Ilana; Sergienko, Ruslan; Sheiner, Eyal

2016-02-01

This study aims to examine whether renal function during pregnancy can serve as a surrogate marker for the risk of developing atherosclerotic-related morbidity. A case-control study, including women who gave birth at a tertiary referral medical centre during 2000-2012. This population was divided into cases of women who were subsequently hospitalized for atherosclerotic morbidity during the study period and age-matched controls. From the study population, we retrieved two groups: the creatinine (Cr) group: women who had at least one Cr measurement (4945 women) and the urea group: women who had at least one urea measurement (4932 women) during their pregnancies. In the Cr and urea group, there were 572 and 571 cases and 4373 and 4361 controls, respectively. The mean follow-up period in the Cr and urea group was 61.7 ± 37.0 and 57.3 ± 36.0 months, respectively. Cox proportional hazards models (controlling for confounders: gestational hypertension, gestational diabetes, obesity, maternal age, creatinine level (for urea), and gestational week) were used to estimate the adjusted hazard ratios (HR) for hospitalizations. A significant association was documented between renal function during pregnancy and long-term atherosclerotic morbidity. Multivariate analysis, showed that Cr at pregnancy index of ≥89 μmol/L was associated with a significant increased risk for hospitalization due to cardiovascular (CVS) events (adjusted HR = 2.91 CI 1.37-6.19 P = 0.005) and urea level ≤7 mmol/L was independently associated with reduced prevalence of CVS hospitalization (adjusted HR = 0.62 CI 0.57-0.86 P = 0.001). Renal function abnormality during pregnancy may reveal occult predisposition to atherosclerotic morbidity years after childbirth. © 2015 Asian Pacific Society of Nephrology.

Mitochondrial DNA damage and vascular function in patients with diabetes mellitus and atherosclerotic cardiovascular disease.

Science.gov (United States)

Fetterman, Jessica L; Holbrook, Monica; Westbrook, David G; Brown, Jamelle A; Feeley, Kyle P; Bretón-Romero, Rosa; Linder, Erika A; Berk, Brittany D; Weisbrod, Robert M; Widlansky, Michael E; Gokce, Noyan; Ballinger, Scott W; Hamburg, Naomi M

2016-03-31

Prior studies demonstrate mitochondrial dysfunction with increased reactive oxygen species generation in peripheral blood mononuclear cells in diabetes mellitus. Oxidative stress-mediated damage to mitochondrial DNA promotes atherosclerosis in animal models. Thus, we evaluated the relation of mitochondrial DNA damage in peripheral blood mononuclear cells s with vascular function in patients with diabetes mellitus and with atherosclerotic cardiovascular disease. We assessed non-invasive vascular function and mitochondrial DNA damage in 275 patients (age 57 ± 9 years, 60 % women) with atherosclerotic cardiovascular disease alone (N = 55), diabetes mellitus alone (N = 74), combined atherosclerotic cardiovascular disease and diabetes mellitus (N = 48), and controls age >45 without diabetes mellitus or atherosclerotic cardiovascular disease (N = 98). Mitochondrial DNA damage measured by quantitative PCR in peripheral blood mononuclear cells was higher with clinical atherosclerosis alone (0.55 ± 0.65), diabetes mellitus alone (0.65 ± 1.0), and combined clinical atherosclerosis and diabetes mellitus (0.89 ± 1.32) as compared to control subjects (0.23 ± 0.64, P < 0.0001). In multivariable models adjusting for age, sex, and relevant cardiovascular risk factors, clinical atherosclerosis and diabetes mellitus remained associated with higher mitochondrial DNA damage levels (β = 0.14 ± 0.13, P = 0.04 and β = 0.21 ± 0.13, P = 0.002, respectively). Higher mitochondrial DNA damage was associated with higher baseline pulse amplitude, a measure of arterial pulsatility, but not with flow-mediated dilation or hyperemic response, measures of vasodilator function. We found greater mitochondrial DNA damage in patients with diabetes mellitus and clinical atherosclerosis. The association of mitochondrial DNA damage and baseline pulse amplitude may suggest a link between mitochondrial dysfunction and excessive small artery pulsatility with potentially adverse microvascular impact.

Serum Asymmetric Dimethylarginine, and Adiponectin as Predictors of Atherosclerotic Risk among Obese Egyptian Children

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Enas R. Abdel Hameed

2014-06-01

CONCLUSIONS: Our results revealed that ADMA, Adiponectin and lipid profile can be considered as predictive biomarkers in prediction and prevention of atherosclerotic risk in the future among overweight and obese Egyptian children.

Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque.

Science.gov (United States)

Bonin, L R; Madden, K; Shera, K; Ihle, J; Matthews, C; Aziz, S; Perez-Reyes, N; McDougall, J K; Conroy, S C

1999-03-01

novel plaque cell lines exhibiting various features of plaque SMC biology; pdSMC2 may represent an earlier plaque SMC phenotype, whereas pdSMC1A may be representative of cells comprising an advanced atherosclerotic lesion.

Telomerase Reverse Transcriptase Deficiency Prevents Neointima Formation Through Chromatin Silencing of E2F1 Target Genes.

Science.gov (United States)

Endorf, Elizabeth B; Qing, Hua; Aono, Jun; Terami, Naoto; Doyon, Geneviève; Hyzny, Eric; Jones, Karrie L; Findeisen, Hannes M; Bruemmer, Dennis

2017-02-01

Aberrant proliferation of smooth muscle cells (SMC) in response to injury induces pathological vascular remodeling during atherosclerosis and neointima formation. Telomerase is rate limiting for tissue renewal and cell replication; however, the physiological role of telomerase in vascular diseases remains to be determined. The goal of the present study was to determine whether telomerase reverse transcriptase (TERT) affects proliferative vascular remodeling and to define the molecular mechanism by which TERT supports SMC proliferation. We first demonstrate high levels of TERT expression in replicating SMC of atherosclerotic and neointimal lesions. Using a model of guidewire-induced arterial injury, we demonstrate decreased neointima formation in TERT-deficient mice. Studies in SMC isolated from TERT-deficient and TERT overexpressing mice with normal telomere length established that TERT is necessary and sufficient for cell proliferation. TERT deficiency did not induce a senescent phenotype but resulted in G1 arrest albeit hyperphosphorylation of the retinoblastoma protein. This proliferative arrest was associated with stable silencing of the E2F1-dependent S-phase gene expression program and not reversed by ectopic overexpression of E2F1. Finally, chromatin immunoprecipitation and accessibility assays revealed that TERT is recruited to E2F1 target sites and promotes chromatin accessibility for E2F1 by facilitating the acquisition of permissive histone modifications. These data indicate a previously unrecognized role for TERT in neointima formation through epigenetic regulation of proliferative gene expression in SMC. © 2016 American Heart Association, Inc.

Endometrial-Peritoneal Interactions during Endometriotic Lesion Establishment

OpenAIRE

Hull, M. Louise; Escareno, Claudia Rangel; Godsland, Jane M.; Doig, John R.; Johnson, Claire M.; Phillips, Stephen C.; Smith, Stephen K.; Tavaré, Simon; Print, Cristin G.; Charnock-Jones, D. Stephen

2008-01-01

The pathophysiology of endometriosis remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesized that disruption of this interaction would suppress endometriotic lesion formation. We hoped to delineate the molecular and cellular dialogue between ectopic human endometrium and peritoneal tissues in nude mice as a first step toward testing this hypothesis. Human endometrium was xenografted into nude mice, and the resulting lesions w...

Treatment of periodontitis improves the atherosclerotic profile : a systematic review and meta-analysis

NARCIS (Netherlands)

Teeuw, Wijnand J.; Slot, Dagmar E.; Susanto, Hendri; Gerdes, Victor E. A.; Abbas, Frank; D'Aiuto, Francesco; Kastelein, John J. P.; Loos, Bruno G.

AimSystematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. Material and MethodsLiterature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials,

Treatment of periodontitis improves the atherosclerotic profile: a systematic review and meta-analysis

NARCIS (Netherlands)

Teeuw, W.J.; Slot, D.E.; Susanto, H.; Gerdes, V.E.A.; Abbas, F.; D'Aiuto, F.; Kastelein, J.J.P.; Loos, B.G.

2014-01-01

Aim Systematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. Material and Methods Literature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials,

Treatment of periodontitis improves the atherosclerotic profile: a systematic review and meta-analysis

NARCIS (Netherlands)

Teeuw, Wijnand J.; Slot, Dagmar E.; Susanto, Hendri; Gerdes, Victor E. A.; Abbas, Frank; D'Aiuto, Francesco; Kastelein, John J. P.; Loos, Bruno G.

2014-01-01

AimSystematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. Material and MethodsLiterature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials,

Ozone sensitivity in hybrid poplar correlates with insensitivity to both salicylic acid and jasmonic acid. The role of programmed cell death in lesion formation.

Science.gov (United States)

Koch, J R; Creelman, R A; Eshita, S M; Seskar, M; Mullet, J E; Davis, K R

2000-06-01

Our earlier studies demonstrated that the ozone-sensitive hybrid poplar clone NE-388 displays an attenuated level of ozone-, wound-, and phytopathogen-induced defense gene expression. To determine if this reduced gene activation involves signal transduction pathways dependent on salicylic acid (SA) and/or jasmonic acid (JA), we compared the responses of NE-388 and an ozone-tolerant clone, NE-245, to these signal molecules. JA levels increased in both clones in response to ozone, but only minimal increases in SA levels were measured for either clone. Treatment with SA and methyl jasmonate induced defense gene expression only in NE-245, indicating that NE-388 is insensitive to these signal molecules. DNA fragmentation, an indicator of programmed cell death (PCD), was detected in NE-245 treated with either ozone or an avirulent phytopathogen, but was not detected in NE-388. We conclude that these clones undergo two distinct mechanisms of ozone-induced lesion formation. In NE-388, lesions appear to be due to toxic cell death resulting from a limited ability to perceive and subsequently activate SA- and/or JA-mediated antioxidant defense responses. In NE-245, SA-dependent PCD precedes lesion formation via a process related to the PCD pathway activated by phytopathogenic bacteria. These results support the hypothesis that ozone triggers a hypersensitive response.

Atherosclerotic vessel damage in systemic lupus erythematosus and antiphospholipid syndrome in men

Directory of Open Access Journals (Sweden)

A. I. Iljina

2005-01-01

Full Text Available Objective. To study prevalence of clinical and subclinical atherosclerosis signs in men with systemic lupus erythematosus (SLE and antiphospholipid syndrome, to assess relationship between atherosclerotic vessel damage, risk factors, CRP and anti-cardiolipin antibodies (АСА Material and methods. 62 pts were included. Mean age was 35,7+11,6 years, mean disease duration - 129,3± 102 months. Traditional and related to the disease risk factors were analyzed. To reveal atherosclerotic vessel damage carotid sonographic examination was performed. Serum CRP concentration was evaluated by high sensitivity nephelometric immunoassay. IgG and IgM АСА were assessed by solid-phase immuno-enzyme assay. Results. Sonographic signs of carotid damage was revealed in 58% of pts, clinical signs of atherosclerosis - in 42%. Pts were divided into two groups according to intima-media complex thickness (IMCT. Group I included 36 pts with atherosclerotic vessel damage signs (IMCT?0,9 mm. Group 2-26 pts with IMCT<0,9 mm. Mean age at the examination, age of disease onset, disease duration, smoking frequency damage index in group I pts were higher than in group 2 pts. Mean CRP concentration in atherosclerosis group was significantly higher than in group 2 (p=0,007. 19 pts had APS signs. 43 pts did not. CRP level significantly correlated with IMCT in SLE pts with and without APS (p<0,05. Pts with atherosclerosis had higher IgG АСА level though the differences were not statistically significant. Conclusion. Men with SLE with or without APS have high risk of atherosclerosis development. CRP elevation is associated with IMCT increase.

Intermittent hypoxia and hypercapnia induce pulmonary artery atherosclerosis and ventricular dysfunction in low density lipoprotein receptor deficient mice

Science.gov (United States)

Bowden, Karen; Pattison, Jennifer; Peterson, Alexander B.; Juliano, Joseph; Dalton, Nancy D.; Gu, Yusu; Alvarez, Erika; Imamura, Toshihiro; Peterson, Kirk L.; Witztum, Joseph L.; Haddad, Gabriel G.; Li, Andrew C.

2013-01-01

Patients with obstructive sleep apnea, who experience episodic hypoxia and hypercapnia during sleep, often demonstrate increased inflammation, oxidative stress, and dyslipidemia. We hypothesized that sleep apnea patients would be predisposed to the development of atherosclerosis. To dissect the mechanisms involved, we developed an animal model in mice whereby we expose mice to intermittent hypoxia/hypercapnia (IHH) in normobaric environments. Two- to three-month-old low-density lipoprotein receptor deficient (Ldlr−/−) mice were fed a high-fat diet for 8 or 16 wk while being exposed to IHH for either 10 h/day or 24 h/day. Plasma lipid levels, pulmonary artery and aortic atherosclerotic lesions, and cardiac function were then assayed. Surprisingly, atherosclerosis in the aorta of IHH mice was similar compared with controls. However, in IHH mice, atherosclerosis was markedly increased in the trunk and proximal branches of the pulmonary artery of exposed mice; even though plasma cholesterol and triglycerides were lower than in controls. Hemodynamic analysis revealed that right ventricular maximum pressure and isovolumic relaxation constant were significantly increased in IHH exposed mice and left ventricular % fractional shortening was reduced. In conclusion, 1) Intermittent hypoxia/hypercapnia remarkably accelerated atherosclerotic lesions in the pulmonary artery of Ldlr−/− mice and 2) increased lesion formation in the pulmonary artery was associated with right and left ventricular dysfunction. These findings raise the possibility that patients with obstructive sleep apnea may be susceptible to atherosclerotic disease in the pulmonary vasculature, an observation that has not been previously recognized. PMID:23990245

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

International Nuclear Information System (INIS)

Karki, Rajendra; Kim, Seong-Bin; Kim, Dong-Wook

2013-01-01

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

Energy Technology Data Exchange (ETDEWEB)

Karki, Rajendra [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City (United States); Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of); Kim, Seong-Bin [Jeollanamdo Development Institute for Korean Traditional Medicine, Jangheung gun, Jeollanamdo (Korea, Republic of); Kim, Dong-Wook, E-mail: dbkim@mokpo.ac.kr [Department of Oriental Medicine Resources, Mokpo National University (Korea, Republic of)

2013-12-10

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti

The role of contrast-enhanced ultrasound in risk assessment of carotid atheroma

Directory of Open Access Journals (Sweden)

Silviu Stanciu

2016-07-01

Full Text Available Background and objective: Contrast-enhanced ultrasound, used to assess atherosclerotic carotid plaques, improves visualization of vessel wall irregularities and depicts intraplaque neovascularization. This article illustrates the use of contrast-enhanced ultrasound in the risk assessment of carotid atherosclerotic lesions, especially in challenging plaques evaluation. Materials and methods: For 23 patients with difficult duplex ultrasound examination due to carotid tortuosity or calcifications we assessed plaque morphology (contour, echogenicity and stenosis degree using contrast substance (Sonovue, Braco with dedicated vascular low mechanical index CPC software. Conclusion: Contrast-enhanced ultrasound is a new, noninvasive, and safe procedure for imaging carotid atherosclerotic lesions. It is a valuable tool for evaluating the vulnerable plaque at risk for rupture and for the diagnostic of the development and severity of systemic atherosclerotic disease

Intensity dependence of focused ultrasound lesion position

Science.gov (United States)

Meaney, Paul M.; Cahill, Mark D.; ter Haar, Gail R.

1998-04-01

Knowledge of the spatial distribution of intensity loss from an ultrasonic beam is critical to predicting lesion formation in focused ultrasound surgery. To date most models have used linear propagation models to predict the intensity profiles needed to compute the temporally varying temperature distributions. These can be used to compute thermal dose contours that can in turn be used to predict the extent of thermal damage. However, these simulations fail to adequately describe the abnormal lesion formation behavior observed for in vitro experiments in cases where the transducer drive levels are varied over a wide range. For these experiments, the extent of thermal damage has been observed to move significantly closer to the transducer with increasing transducer drive levels than would be predicted using linear propagation models. The simulations described herein, utilize the KZK (Khokhlov-Zabolotskaya-Kuznetsov) nonlinear propagation model with the parabolic approximation for highly focused ultrasound waves, to demonstrate that the positions of the peak intensity and the lesion do indeed move closer to the transducer. This illustrates that for accurate modeling of heating during FUS, nonlinear effects must be considered.

Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice

Energy Technology Data Exchange (ETDEWEB)

Nakamura, Ikuko, E-mail: nakamuri@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Cardiovascular Medicine, Saga University, Saga (Japan); Hasegawa, Koki [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Pathology and Experimental Medicine, Kumamoto University, Kumamoto (Japan); Wada, Yasuhiro [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Hirase, Tetsuaki; Node, Koichi [Department of Cardiovascular Medicine, Saga University, Saga (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan)

2013-03-29

Highlights: ► P-selectin regulates leukocyte recruitment as an early stage event of atherogenesis. ► We developed an antibody-based molecular imaging probe targeting P-selectin for PET. ► This is the first report on successful PET imaging for delineation of P-selectin. ► P-selectin is a candidate target for atherosclerotic plaque imaging by clinical PET. -- Abstract: Background: Sensitive detection and qualitative analysis of atherosclerotic plaques are in high demand in cardiovascular clinical settings. The leukocyte–endothelial interaction mediated by an adhesion molecule P-selectin participates in arterial wall inflammation and atherosclerosis. Methods and results: A {sup 64}Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated anti-P-selectin monoclonal antibody ({sup 64}Cu-DOTA-anti-P-selectin mAb) probe was prepared by conjugating an anti-P-selectin monoclonal antibody with DOTA followed by {sup 64}Cu labeling. Thirty-six hours prior to PET and CT fusion imaging, 3 MBq of {sup 64}Cu-DOTA-anti-P-selectin mAb was intravenously injected into low density lipoprotein receptor-deficient Ldlr-/- mice. After a 180 min PET scan, autoradiography and biodistribution of {sup 64}Cu-DOTA-anti-P-selectin monoclonal antibody was examined using excised aortas. In Ldlr-/- mice fed with a high cholesterol diet for promotion of atherosclerotic plaque development, PET and CT fusion imaging revealed selective and prominent accumulation of the probe in the aortic root. Autoradiography of aortas that demonstrated probe uptake into atherosclerotic plaques was confirmed by Oil red O staining for lipid droplets. In Ldlr-/- mice fed with a chow diet to develop mild atherosclerotic plaques, probe accumulation was barely detectable in the aortic root on PET and CT fusion imaging. Probe biodistribution in aortas was 6.6-fold higher in Ldlr-/- mice fed with a high cholesterol diet than in those fed with a normal chow diet. {sup 64}Cu-DOTA-anti-P-selectin m

Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability

International Nuclear Information System (INIS)

Müller, Adrienne; Krämer, Stefanie D.; Meletta, Romana; Beck, Katharina; Selivanova, Svetlana V.; Rancic, Zoran; Kaufmann, Philipp A.; Vos, Bernhard; Meding, Jörg; Stellfeld, Timo; Heinrich, Tobias K.; Bauser, Marcus; Hütter, Joachim; Dinkelborg, Ludger M.; Schibli, Roger; Ametamey, Simon M.

2014-01-01

Introduction: Atherosclerotic plaque rupture is the primary cause for myocardial infarction and stroke. During plaque progression macrophages and mast cells secrete matrix-degrading proteolytic enzymes, such as matrix metalloproteinases (MMPs). We studied levels of MMPs and tissue inhibitor of metalloproteinases-3 (TIMP-3) in relation to the characteristics of carotid plaques. We evaluated in vitro two radiolabeled probes targeting active MMPs towards non-invasive imaging of rupture-prone plaques. Methods: Human carotid plaques obtained from endarterectomy were classified into stable and vulnerable by visual and histological analysis. MMP-1, MMP-2, MMP-8, MMP-9, MMP-10, MMP-12, MMP-14, TIMP-3, and CD68 levels were investigated by quantitative polymerase chain reaction. Immunohistochemistry was used to localize MMP-2 and MMP-9 with respect to CD68-expressing macrophages. Western blotting was applied to detect their active forms. A fluorine-18-labeled MMP-2/MMP-9 inhibitor and a tritiated selective MMP-9 inhibitor were evaluated by in vitro autoradiography as potential lead structures for non-invasive imaging. Results: Gene expression levels of all MMPs and CD68 were elevated in plaques. MMP-1, MMP-9, MMP-12 and MMP-14 were significantly higher in vulnerable than stable plaques. TIMP-3 expression was highest in stable and low in vulnerable plaques. Immunohistochemistry revealed intensive staining of MMP-9 in vulnerable plaques. Western blotting confirmed presence of the active form in plaque lysates. In vitro autoradiography showed binding of both inhibitors to stable and vulnerable plaques. Conclusions: MMPs differed in their expression patterns among plaque phenotypes, providing possible imaging targets. The two tested MMP-2/MMP-9 and MMP-9 inhibitors may be useful to detect atherosclerotic plaques, but not the vulnerable lesions selectively

Ozone Sensitivity in Hybrid Poplar Correlates with Insensitivity to Both Salicylic Acid and Jasmonic Acid. The Role of Programmed Cell Death in Lesion Formation1

Science.gov (United States)

Koch, Jennifer Riehl; Creelman, Robert A.; Eshita, Steven M.; Seskar, Mirjana; Mullet, John E.; Davis, Keith R.

2000-01-01

Our earlier studies demonstrated that the ozone-sensitive hybrid poplar clone NE-388 displays an attenuated level of ozone-, wound-, and phytopathogen-induced defense gene expression. To determine if this reduced gene activation involves signal transduction pathways dependent on salicylic acid (SA) and/or jasmonic acid (JA), we compared the responses of NE-388 and an ozone-tolerant clone, NE-245, to these signal molecules. JA levels increased in both clones in response to ozone, but only minimal increases in SA levels were measured for either clone. Treatment with SA and methyl jasmonate induced defense gene expression only in NE-245, indicating that NE-388 is insensitive to these signal molecules. DNA fragmentation, an indicator of programmed cell death (PCD), was detected in NE-245 treated with either ozone or an avirulent phytopathogen, but was not detected in NE-388. We conclude that these clones undergo two distinct mechanisms of ozone-induced lesion formation. In NE-388, lesions appear to be due to toxic cell death resulting from a limited ability to perceive and subsequently activate SA- and/or JA-mediated antioxidant defense responses. In NE-245, SA-dependent PCD precedes lesion formation via a process related to the PCD pathway activated by phytopathogenic bacteria. These results support the hypothesis that ozone triggers a hypersensitive response. PMID:10859179

Extracts of human atherosclerotic lesions modify LDL inducing enhanced macrophage uptake

International Nuclear Information System (INIS)

Hoff, H.F.; O'Neill, J.

1986-01-01

Both an LDL-like fraction isolated from human aortic plaques and LDL incubated with cultured aortic endothelial or smooth muscle cells have been shown to be internalized by macrophages in vitro in an unregulated fashion leading to foam cell formation. Lipid peroxidation induced by free radicals released from cells was shown to be responsible for cell-modified LDL. The authors incubated LDL with a supernatant fraction of leached, i.e. non-homogenized, extracts of aortic plaques for one hour at 37 0 C, to determine whether extracellular components present in arteries were also capable of modifying LDL. Extract-treated LDL showed the following changes relative to untreated LDL: 1) increased electrophretic mobility, 2) altered pattern of B-100 on SDS-PAGE, i.e. presence of a doublet with higher M/sub r/ than B-100, and 3) enhanced uptake by cultured mouse peritoneal macrophages as measured by increased degradation of 125 I-LDL, and increased stimulation of cholesterol esterification using 14 C-oleate. Extracts from homogenized plaques and grossly normal intima induced similar changes. The modification was tissue specific in that extracts of arteries but not of liver, muscle or skin modified LDL. Protease degradation of LDL during incubation was probably not responsible since inhibitors did not prevent modification. It is possible that products of lipid peroxidation present in extracellular lipid of arteries may propagate free radicals or be incorporated into LDL, leading to modifications similar to those found in cell-modified LDL

Using passive cavitation images to classify high-intensity focused ultrasound lesions.

Science.gov (United States)

Haworth, Kevin J; Salgaonkar, Vasant A; Corregan, Nicholas M; Holland, Christy K; Mast, T Douglas

2015-09-01

Passive cavitation imaging provides spatially resolved monitoring of cavitation emissions. However, the diffraction limit of a linear imaging array results in relatively poor range resolution. Poor range resolution has limited prior analyses of the spatial specificity and sensitivity of passive cavitation imaging in predicting thermal lesion formation. In this study, this limitation is overcome by orienting a linear array orthogonal to the high-intensity focused ultrasound propagation direction and performing passive imaging. Fourteen lesions were formed in ex vivo bovine liver samples as a result of 1.1-MHz continuous-wave ultrasound exposure. The lesions were classified as focal, "tadpole" or pre-focal based on their shape and location. Passive cavitation images were beamformed from emissions at the fundamental, harmonic, ultraharmonic and inharmonic frequencies with an established algorithm. Using the area under a receiver operating characteristic curve (AUROC), fundamental, harmonic and ultraharmonic emissions were found to be significant predictors of lesion formation for all lesion types. For both harmonic and ultraharmonic emissions, pre-focal lesions were classified most successfully (AUROC values of 0.87 and 0.88, respectively), followed by tadpole lesions (AUROC values of 0.77 and 0.64, respectively) and focal lesions (AUROC values of 0.65 and 0.60, respectively). Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Imaging arterial cells, atherosclerosis, and restenosis by multimodal nonlinear optical microscopy

Science.gov (United States)

Wang, Han-Wei; Simianu, Vlad; Locker, Matthew J.; Sturek, Michael; Cheng, Ji-Xin

2008-02-01

By integrating sum-frequency generation (SFG), and two-photon excitation fluorescence (TPEF) on a coherent anti-Stokes Raman scattering (CARS) microscope platform, multimodal nonlinear optical (NLO) imaging of arteries and atherosclerotic lesions was demonstrated. CARS signals arising from CH II-rich membranes allowed visualization of endothelial cells and smooth muscle cells in a carotid artery. Additionally, CARS microscopy allowed vibrational imaging of elastin and collagen fibrils which are rich in CH II bonds in their cross-linking residues. The extracellular matrix organization was further confirmed by TPEF signals arising from elastin's autofluorescence and SFG signals arising from collagen fibrils' non-centrosymmetric structure. The system is capable of identifying different atherosclerotic lesion stages with sub-cellular resolution. The stages of atherosclerosis, such as macrophage infiltration, lipid-laden foam cell accumulation, extracellular lipid distribution, fibrous tissue deposition, plaque establishment, and formation of other complicated lesions could be viewed by our multimodal CARS microscope. Collagen percentages in the region adjacent to coronary artery stents were resolved. High correlation between NLO and histology imaging evidenced the validity of the NLO imaging. The capability of imaging significant components of an arterial wall and distinctive stages of atherosclerosis in a label-free manner suggests the potential application of multimodal nonlinear optical microscopy to monitor the onset and progression of arterial diseases.

Vascular morphologic and functional effect of endogenous androgens in an experimental atherosclerotic rabbits model

International Nuclear Information System (INIS)

Echeverry, Dario; Delgadillo, Alexandra; Montes, Felix

2007-01-01

Previous clinical and experimental studies suggest that androgens could have adverse, neutral or beneficial effect on atherosclerosis and its clinical manifestations. Methods: an experimental, randomized controlled study in 40 New Zeland white male rabbits was realized. 20 rabbits underwent orchidectomy and 20 were fed with an atherogenic diet for 20 weeks. These were distributed in four groups: 1. non-castrated under normal diet, 2. Castrated under normal diet, 3. non-castrated under atherogenic diet, and 4. Castrated under atherogenic diet. Total cholesterol and free testosterone were measured. After euthanasia, arterial relaxation independent of endothelium was quantified in aorta, as well as the one depending on endothelium, in vitro, and histomorphometric analysis of thoracic aorta were made in order to quantify the atherosclerotic plaque formation. Results: animals that had a normal diet (n=20) had total cholesterol of 51.1 ± 8.5 mg/dl and those with atherogenic diet of 429.2 ± 262.0 mg/dl (p< 0.001). Testosterone levels in the non- castrated group were 2.1 ± 0.3 ng/ml and in the castrated were 0.8 ± 0.4 ng/ml (p= 0.024). In non-castrated rabbits the effect of hypercholesterolemia (366 ± 226.1 mg/dl) inducing atherosclerotic plaque and functional vascular alteration was mild. On the other hand, atherogenic diet in castrated rabbits induced an increment in total cholesterol from 387.6 ± 292.7 mg/dl (p <0.001) and severe morphological changes such as plaque area 2.6 ± 2.3mm (p <0.001), vessel plaque/area 0.25 ± 0.1 (p <0.001) and area index of plaque/area of the media 0.4 ± 0.3 (p <0.001). Endothelium independent relaxation percentage was 85.5 ± 14.3% (p = NS) and endothelium dependent relaxation was 38.5 ± 201% (p = 0.03). Conclusion: This study realized in rabbits demonstrates that endogenous testosterone might have a preventive effect on atherosclerosis and favor endothelium dependent vascular relaxation in the presence of severe

Magnetic resonance imaging of vulnerable atherosclerotic plaques: current imaging strategies and molecular imaging probes

NARCIS (Netherlands)

Briley-Saebo, Karen C.; Mulder, Willem J. M.; Mani, Venkatesh; Hyafil, Fabien; Amirbekian, Vardan; Aguinaldo, Juan Gilberto S.; Fisher, Edward A.; Fayad, Zahi A.

2007-01-01

The vulnerability or destabilization of atherosclerotic plaques has been directly linked to plaque composition. Imaging modalities, such as magnetic resonance (MR) imaging, that allow for evaluation of plaque composition at a cellular and molecular level, could further improve the detection of

Imaging the Intracranial Atherosclerotic Vessel Wall Using 7T MRI : Initial Comparison with Histopathology

NARCIS (Netherlands)

van der Kolk, A. G.; Zwanenburg, J. J. M.; Denswil, N. P.; Vink, A.; Spliet, W. G. M.; Daemen, M. J. A. P.; Visser, F.; Klomp, D. W. J.; Luijten, P. R.; Hendrikse, J.

In this preliminary study, 7T imaging was capable of identifying not only intracranial wall thickening but different plaque components such as foamy macrophages and collagen. Signal heterogeneity was typical of advanced atherosclerotic disease. BACKGROUND AND PURPOSE: Several studies have attempted

The gut microbiome in atherosclerotic cardiovascular disease

DEFF Research Database (Denmark)

Jie, Zhuye; Xia, Huihua; Zhong, Shi-Long

2017-01-01

The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals...... with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular...... health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes...

Diagnosing extracranial atherosclerotic diseases with spiral CT

International Nuclear Information System (INIS)

Moran, C.J.; Vannier, M.W.; Erickson, K.K.; Broderick, D.F.; Kido, D.K.; Yoffie, R.L.

1991-01-01

This paper reports that this discovery study was performed to determine whether extracranial carotid artery plaques could be diagnosed with a new CT technique (spiral CT) that allows nondistorted three-dimensional (3D) reconstructions in the z axis. Twenty carotid arteries were examined with spiral CT in normal volunteers and in patients suspected of having atherosclerotic plaques in the extracranial carotid arteries. The Somatom Plus CT table was advanced at a constant rate, the x-ray tube was continuously rotated, and 3D data were continuously acquired. Sixty milliliters of nonionic contrast medium was injected intravenously previous to and during the acquisition of data. The carotid bifurcations were identified in all patients. Planar images, similar to conventional intraarterial angiograms, were routinely produced from the volumetric CT data

Atherosclerotic plaque component segmentation in combined carotid MRI and CTA data incorporating class label uncertainty

DEFF Research Database (Denmark)

van Engelen, Arna; Niessen, Wiro J.; Klein, Stefan

2014-01-01

Atherosclerotic plaque composition can indicate plaque vulnerability. We segment atherosclerotic plaque components from the carotid artery on a combination of in vivo MRI and CT-angiography (CTA) data using supervised voxelwise classification. In contrast to previous studies the ground truth...... for training is directly obtained from 3D registration with histology for fibrous and lipid-rich necrotic tissue, and with [Formula: see text]CT for calcification. This registration does, however, not provide accurate voxelwise correspondence. We therefore evaluate three approaches that incorporate uncertainty......), II) samples are weighted by the local contour distance of the lumen and outer wall between histology and in vivo data, and III) 10% of each class is rejected by Gaussian outlier rejection. Classification was evaluated on the relative volumes (% of tissue type in the vessel wall) for calcified...

Tensile and compressive properties of fresh human carotid atherosclerotic plaques.

LENUS (Irish Health Repository)

Maher, Eoghan

2009-12-11

Accurate characterisation of the mechanical properties of human atherosclerotic plaque is important for our understanding of the role of vascular mechanics in the development and treatment of atherosclerosis. The majority of previous studies investigating the mechanical properties of human plaque are based on tests of plaque tissue removed following autopsy. This study aims to characterise the mechanical behaviour of fresh human carotid plaques removed during endarterectomy and tested within 2h. A total of 50 radial compressive and 17 circumferential tensile uniaxial tests were performed on samples taken from 14 carotid plaques. The clinical classification of each plaque, as determined by duplex ultrasound is also reported. Plaques were classified as calcified, mixed or echolucent. Experimental data indicated that plaques were highly inhomogeneous; with variations seen in the mechanical properties of plaque obtained from individual donors and between donors. The mean behaviour of samples for each classification indicated that calcified plaques had the stiffest response, while echolucent plaques were the least stiff. Results also indicated that there may be a difference in behaviour of samples taken from different anatomical locations (common, internal and external carotid), however the large variability indicates that more testing is needed to reach significant conclusions. This work represents a step towards a better understanding of the in vivo mechanical behaviour of human atherosclerotic plaque.

Athero Express : ATHERO-sclerotic plaque EXPRESSion in relation to vascular events and patient characteristics

NARCIS (Netherlands)

Verhoeven, B.A.N.

2006-01-01

Athero-Express is a tissue bank study, designed to investigate the expression of atherosclerotic derived biological variables in relation to the long-term outcome of patients undergoing carotid endarterectomy. Its design includes both cross-sectional and follow-up studies, the results from which

Imaging the intracranial atherosclerotic vessel wall using 7T MRI: initial comparison with histopathology

NARCIS (Netherlands)

van der Kolk, A. G.; Zwanenburg, J. J. M.; Denswil, N. P.; Vink, A.; Spliet, W. G. M.; Daemen, M. J. A. P.; Visser, F.; Klomp, D. W. J.; Luijten, P. R.; Hendrikse, J.

2015-01-01

Several studies have attempted to characterize intracranial atherosclerotic plaques by using MR imaging sequences. However, dedicated validation of these sequences with histology has not yet been performed. The current study assessed the ability of ultra-high-resolution 7T MR imaging sequences with

Ophthalmic masquerades of the atherosclerotic carotids

Directory of Open Access Journals (Sweden)

Anupriya Arthur

2014-01-01

Full Text Available Patients with carotid atherosclerosis can present with ophthalmic symptoms. These symptoms and signs can be due to retinal emboli, hypoperfusion of the retina and choroid, opening up of collateral channels, or chronic hypoperfusion of the globe (ocular ischemic syndrome. These pathological mechanisms can produce many interesting signs and a careful history can bring out important past symptoms pointing toward the carotid as the source of the patient′s presenting symptom. Such patients are at high risk for an ischemic stroke, especially in the subsequent few days following their first acute symptom. It is important for clinicians to be familiar with these ophthalmic symptoms and signs caused by carotid atherosclerosis for making an early diagnosis and to take appropriate measures to prevent a stroke. This review elaborates the clinical features, importance, and implications of various ophthalmic symptoms and signs resulting from atherosclerotic carotid artery disease.

Snoring and atherosclerotic manifestations in a 70-year-old population

DEFF Research Database (Denmark)

Jennum, P; Schultz-Larsen, K; Christensen, N J

1996-01-01

the issue we examined the association between self-assessed snoring and the relation to atherosclerotic manifestations. 804 70-year-old males and females were classified according to snoring habits. Alcohol and tobacco consumption, blood pressure, body mass index, social group, plasma lipids (triglycerides......, cholesterol, high density lipoprotein), fasting blood glucose, glucose tolerance test, plasma epinephrine and norepinephrine were determined. Presence of angina pectoris, claudication intermittens, use of nitroglycerine were questioned, a resting ECG and a distal arterial pressure by use of doppler technique...

Evaluation of the early enhancement of coronary atherosclerotic plaque by contrast-enhanced MR angiography

Energy Technology Data Exchange (ETDEWEB)

Li Tao [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhao Xihai [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Liu Xin [Paul C. Lauterbur Biomedical Imaging Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen 518067 (China); Gao Jianhua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Zhao Shaohong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Li Xin; Zhou Weihua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Cai Zulong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhang Weiguo [Cardiovascular and Neurological Consulting Institute, 6771 San Fernando, Irving, TX 75039 (United States); Yang Li, E-mail: Yangli301@yahoo.com [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China)

2011-10-15

Purpose: To evaluate the early enhancement of coronary atherosclerotic plaque using contrast-enhanced MR angiography (CE-MRA) and investigate the association between unstable angina pectoris (UAP) and early enhancement of the plaque. Methods: Forty-one patients presenting with angina pectoris and demonstrating single-vessel disease with non-calcified plaque and significant coronary stenosis ({>=}50%) on CTA were consecutively recruited for coronary CE-MRA. Contrast-to-noise ratio of the culprit plaque guided by CTA was measured on a cross-sectional multi-planar reconstruction image of the plaque on both pre- and post-CE-MRA. A 50% increasing of CNR was defined as plaque enhancement. The association between early enhancement of the plaques and UAP was analyzed. Results: Thirty-seven non-calcified plaques with significant coronary stenosis were detected in the 37 patients on MRA. 4 subjects were excluded because coronary atherosclerotic plaques were inadequate for identification on MRA. Of the 37 patients, 18 patients had UAP and other 19 patients presented stable angina pectoris (SAP). Of the 37 plaques on CE-MRA, 13 and 24 plaques presented early enhancement and no enhancement, respectively. Of the 13 early-enhanced plaques, 11 (85%) and 2 (15%) were found in the patients with UAP and SAP, respectively (p < 0.01). Of the 37 patients, 11 (61%) with UAP and 2 (11%) with SAP had early-enhanced plaques, respectively (p < 0.01). Conclusion: CE-MRA allows detection of early enhancement of coronary atherosclerotic plaque. The early enhancement is common in unstable angina and could be a sign of vulnerability.

The gut microbiome in atherosclerotic cardiovascular disease

DEFF Research Database (Denmark)

Jie, Zhuye; Xia, Huihua; Zhong, Shi-Long

2017-01-01

The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals...... with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular......), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform...

Quantification of plaque area and characterization of plaque biochemical composition with atherosclerosis progression in ApoE/LDLR(-/-) mice by FT-IR imaging.

Science.gov (United States)

Wrobel, Tomasz P; Mateuszuk, Lukasz; Kostogrys, Renata B; Chlopicki, Stefan; Baranska, Malgorzata

2013-11-07

In this work the quantitative determination of atherosclerotic lesion area (ApoE/LDLR(-/-) mice) by FT-IR imaging is presented and validated by comparison with atherosclerotic lesion area determination by classic Oil Red O staining. Cluster analysis of FT-IR-based measurements in the 2800-3025 cm(-1) range allowed for quantitative analysis of the atherosclerosis plaque area, the results of which were highly correlated with those of Oil Red O histological staining (R(2) = 0.935). Moreover, a specific class obtained from a second cluster analysis of the aortic cross-section samples at different stages of disease progression (3, 4 and 6 months old) seemed to represent the macrophages (CD68) area within the atherosclerotic plaque.

Serum-Sphingosine-1-Phosphate Concentrations Are Inversely Associated with Atherosclerotic Diseases in Humans.

Directory of Open Access Journals (Sweden)

Irina Soltau

Full Text Available Atherosclerotic changes of arteries are the leading cause for deaths in cardiovascular disease and greatly impair patient's quality of life. Sphingosine-1-phosphate (S1P is a signaling sphingolipid that regulates potentially pro-as well as anti-atherogenic processes. Here, we investigate whether serum-S1P concentrations are associated with peripheral artery disease (PAD and carotid stenosis (CS.Serum was sampled from blood donors (controls, N = 174 and from atherosclerotic patients (N = 132 who presented to the hospital with either clinically relevant PAD (N = 102 or CS (N = 30. From all subjects, serum-S1P was measured by mass spectrometry and blood parameters were determined by routine laboratory assays. When compared to controls, atherosclerotic patients before invasive treatment to restore blood flow showed significantly lower serum-S1P levels. This difference cannot be explained by risk factors for atherosclerosis (old age, male gender, hypertension, hypercholesteremia, obesity, diabetes or smoking or comorbidities (Chronic obstructive pulmonary disease, kidney insufficiency or arrhythmia. Receiver operating characteristic curves suggest that S1P has more power to indicate atherosclerosis (PAD and CS than high density lipoprotein-cholesterol (HDL-C. In 35 patients, serum-S1P was measured again between one and six months after treatment. In this group, serum-S1P concentrations rose after treatment independent of whether patients had PAD or CS, or whether they underwent open or endovascular surgery. Post-treatment S1P levels were highly associated to platelet numbers measured pre-treatment.Our study shows that PAD and CS in humans is associated with decreased serum-S1P concentrations and that S1P may possess higher accuracy to indicate these diseases than HDL-C.

Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

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Patrik Htun

Full Text Available Since patients with phenylketonuria (PKU have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT and ß-stiffness index] and platelet activation.In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation. CIMT was measured bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of CIMTleft and CIMTright.Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group.Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients.

Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

Science.gov (United States)

Htun, Patrik; Nee, Jens; Ploeckinger, Ursula; Eder, Klaus; Geisler, Tobias; Gawaz, Meinrad; Bocksch, Wolfgang; Fateh-Moghadam, Suzanne

2015-01-01

Since patients with phenylketonuria (PKU) have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT) and ß-stiffness index] and platelet activation. In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation). CIMT was measured bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of CIMTleft and CIMTright. Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group. Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients.

The EPIC nitinol stent system in the treatment of iliac artery lesions: one-year results from the ORION clinical trial.

Science.gov (United States)

Clair, Daniel G; Adams, Julie; Reen, Bernard; Feldman, Robert; Starr, Jean; Diaz-Cartelle, Juan; Dawkins, Keith D

2014-04-01

To report the 1-year results of a pivotal study for a new-generation nitinol stent for the treatment of iliac atherosclerotic lesions. The ORION trial (ClinicalTrials.gov identifier NCT00896337) was a single-arm, non-randomized, prospective, multicenter clinical trial that enrolled 125 patients (81 men; mean age 61.1±9.3 years) implanted with the EPIC self-expanding nitinol stent system in 166 de novo or restenotic iliac artery lesions ≤13 cm long. The primary endpoint was the 9-month major adverse event rate [i.e., device- or procedure-related death within 30 days, myocardial infarction during the index hospitalization, target vessel revascularization (TVR), or index limb amputation]. Follow-up occurred at hospital discharge and at 1, 9, and 12 months. An independent core laboratory evaluated ultrasound results at 1, 9, and 12 months. The primary endpoint met the prespecified performance goal, with only 3.4% (4/117) of patients experiencing a major adverse event by 9 months (p<0.0001). By 12 months, 6 (5.4%) of 111 patients had TVR; none had an index limb amputation. The ankle-brachial index, Walking Impairment Questionnaire, and Rutherford classifications all showed sustained improvements through 12 months. Primary patency was 94.4% with comparable results for lesions classified as complex (TASC II C/D 95.5%) or non-complex (TASC II A/B 95.0%). The EPIC stent system demonstrated safety and effectiveness through 12 months, including improvements for complex lesions. The EPIC stent is a viable alternative to surgery for patients with either complex or non-complex lesions.

DYNAMICS OF HIGHGER MENTAL FUNCTION IN PATIENTS WITH OBLITERATING LESIONS OF INTERNAL CAROTID ARTERIES IN SURGICAL BRAIN REVASCUL

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R. A. Vinogradov

2017-01-01

Full Text Available Obliterating atherosclerosis of internal carotid arteries is one of the main causes of ischemic stroke and discirculatory encephalopathy. It causes up to 40% of ischemic disorders of cerebral circulation. Currently, the strategy for stroke prevention is determined by the intensive development of surgical methods of treatment, primarily methods for managing lesions of brachiocephalic arteries. Based on the results of a number of international multicenter randomized studies, indications for reconstructive operations for BCA, tactics for managing patients in the postoperative period were formulated. A number of patients with atherosclerotic lesions of brachiocephalic arteries have reduced cognitive functions. The aim of the study is to compare cognitive functions (CF in patients who underwent different surgical approaches in the treatment of obliterating atherosclerotic lesion of internal carotid arteries (ICA.MATERIAL AND METHODS. We studied higher mental functions (HMFs in 116 patients with obliterating unilateral or bilateral lesion of ICA. The study of cognitive functions (MF was performed prior to carotid endarterectomy (CE, group 1, n=73 and transluminal balloon angioplasty of ICAs (TBA of ICA, group 2, n=43, and on days 5–7 and 30–31 after cerebral revascularization (CR. To assess the overall severity of cognitive impairment, the summary indicators of main screening neuropsychological tests were used: MMSE; MoCA; Frontal Assessment Battery (FAB; Beck Depression Inventory and Hamilton Depression Rating Scale.RESULTS. Results Neuropsychologic disorders were reavealed in 98% of patients prior to surgery. An initially comparable condition of HMF in groups with CE and TBA of ICA was revealed. MMSE2 revealed a significant improvement in the results in group 1 both in comparison with the initial data (p<0.05 and in comparison with the results of the second test of group 2. The results of MMSE1 and MMSE2 in group 2 did not show significant

Can a Morel-Lavallée lesion be misdiagnosed as a mass like lesion?

Science.gov (United States)

Lee, Yoon Jae; Kim, Jun Hyeok; Kim, Ji Young; Han, Hyun Ho

2017-12-01

The Morel-Lavallée lesion (MLL) is a post-traumatic closed soft tissue degloving injury. Common complaints of MLL patients are a haematoma or fluid collection on the trunk or the lower extremity. However, the authors introduce unique cases of MLL that present an atypical appearance. The fluid collection was not apparent, and the capsule formation was not detected on preoperative image study. The main complaint of patients was the uncomfortable mass-like lesion that was regarded as a simple benign lump. The purpose of this case study is to introduce the atypical cases of MLL and to help other physicians make accurate diagnosis based on trial and error of our cases. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Nuclear microprobe investigation into the trace elemental contents of carotid artery walls of apolipoprotein E deficient mice

International Nuclear Information System (INIS)

Ren Minqin; Huang En; Beck, Konstanze; Rajendran, Reshmi; Wu, Ben J.; Halliwell, Barry; Watt, Frank; Stocker, Roland

2007-01-01

Atherosclerosis is a progressive disease that causes lesions in large and medium-sized arteries. There is increasing evidence that the function of vascular endothelial cells is impaired by oxidation reactions, and that metal ions may participate in these processes. The nuclear microscopy facility in NUS, which has the ability to focus a 2 MeV proton beam down to sub micron spot sizes, was used to investigate the trace elemental changes (e.g. Zn and Fe) in atherosclerotic lesions in the common carotid artery of apolipoprotein E deficient mice fed a high fat diet. In this preliminary study, which is part of a larger study to investigate the effects of probucol on carotid artery atherosclerosis, two sets of mice were used; a test set fed a high fat diet +1% probucol, and a control set which was fed a high fat diet only. The results show that the Zn/Fe ratio was significantly higher in the media of arteries of probucol treated animals without overlying lesion (4.3) compared to the media with overlying lesion (1.3) (p = 0.004) for test mice. For the control mice, the arterial Zn/Fe ratio was 1.8 for media without overlying lesion, compared with 1.0 for media with overlying lesion (p = 0.1). Thus, for media without overlying lesion, the Zn/Fe ratio was significantly higher (p = 0.009) in probucol-treated (4.3) than control mice (1.8), whereas there was little difference in the ratios between the two groups in media with overlying lesion (1.3 compared with 1.0). These preliminary results are consistent with the idea that the levels of iron and zinc concentrations within the artery wall may influence the formation of atherosclerotic plaque in the carotid artery

Scintigraphic detection of carotid atherosclerosis with indium-111-labeled autologous platelets

International Nuclear Information System (INIS)

Davis, H.H.; Siegel, B.A.; Sherman, L.A.; Heaton, W.A.; Naidich, T.P.; Joist, J.R.; Welch, M.J.

1980-01-01

Using autologous platelets labeled with indium-111-oxine, we studied the localization of platelets on arterial lesions by radionuclide scintigraphy in 34 patients with suspected cerebrovascular disease. The imaging results were compared with the findings of contrast angiography in 23 patients, 16 of whom were receiving antiplatelet and/or anticoagulant drugs during the platelet imaging study. Angiography demonstrated atherosclerotic lesions at 33 sites in the extracranial arteries of 16 of these patients. There was accumulation of 111 In-platelets at 20 of these sites (61%) and at three other sites without definite angiographic abnormalities. Lesions with stenoses 111 In-labeled autologous platelets may be useful for evaluating the pathophysiologic characteristics of atherosclerotic lesions in patients with cerebrovascular disease

Proliferating macrophages prevail in atherosclerosis.

Science.gov (United States)

Randolph, Gwendalyn J

2013-09-01

Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment of circulating monocytes.

GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules

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Ying Yang

2014-04-01

Full Text Available Aims: γ-aminobutyric acid (GABA, the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs. Methods: ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model. Results: GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-a was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL-6 did not change. The activation of two signaling pathways, p38MAPK and NF-γB, was repressed by GABA and topiramate in lipid-laden HMDMs. Conclusion: GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions.

Cadmium exposure and atherosclerotic carotid plaques –Results from the Malmö diet and Cancer study

International Nuclear Information System (INIS)

Fagerberg, Björn; Barregard, Lars; Sallsten, Gerd; Forsgard, Niklas; Östling, Gerd; Persson, Margaretha; Borné, Yan

2015-01-01

Background: Epidemiological studies indicate that cadmium exposure through diet and smoking is associated with increased risk of cardiovascular disease. There are few data on the relationship between cadmium and plaques, the hallmark of underlying atherosclerotic disease. Objectives: To examine the association between exposure to cadmium and the prevalence and size of atherosclerotic plaques in the carotid artery. Methods: A population sample of 4639 Swedish middle-aged women and men was examined in 1991–1994. Carotid plaque was determined by B-mode ultrasound. Cadmium in blood was analyzed by inductively coupled plasma mass spectrometry. Results: Comparing quartile 4 with quartile 1 of blood cadmium, the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6–2.2) after adjustment for sex and, age; 1.4 (1.1–1.8) after additional adjustment for smoking status; 1.4 (1.1–1.7) after the addition of education level and life style factors; 1.3 (1.03–1.8) after additional adjustment for risk factors and predictors of cardiovascular disease. No effect modification by sex was found in the cadmium-related prevalence of plaques. Similarly, ORs for the prevalence of small and large plaques were after full adjustment 1.4 (1.0–2.1) and 1.4 (0.9–2.0), respectively. The subgroup of never smokers showed no association between cadmium and atherosclerotic plaques. Conclusions: These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans. The role of smoking remains unclear. It may both cause residual confounding and be a source of pro-atherogenic cadmium exposure. - Highlights: • Blood cadmium level is associated with atherosclerotic plaques in the carotid artery. • The results extend previous knowledge of cadmium exposure and clinical events. • The role of smoking remains unclear

Increased metabolite levels of glycolysis and pentose phosphate pathway in rabbit atherosclerotic arteries and hypoxic macrophage.

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Atsushi Yamashita

Full Text Available AIMS: Inflammation and possibly hypoxia largely affect glucose utilization in atherosclerotic arteries, which could alter many metabolic systems. However, metabolic changes in atherosclerotic plaques remain unknown. The present study aims to identify changes in metabolic systems relative to glucose uptake and hypoxia in rabbit atherosclerotic arteries and cultured macrophages. METHODS: Macrophage-rich or smooth muscle cell (SMC-rich neointima was created by balloon injury in the iliac-femoral arteries of rabbits fed with a 0.5% cholesterol diet or a conventional diet. THP-1 macrophages stimulated with lipopolysaccharides (LPS and interferon-γ (INFγ were cultured under normoxic and hypoxic conditions. We evaluated comprehensive arterial and macrophage metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using (18F-fluorodeoxyglucose ((18F-FDG and pimonidazole, a marker of hypoxia. RESULTS: The levels of many metabolites increased in the iliac-femoral arteries with macrophage-rich neointima, compared with those that were not injured and those with SMC-rich neointima (glycolysis, 4 of 9; pentose phosphate pathway, 4 of 6; tricarboxylic acid cycle, 4 of 6; nucleotides, 10 of 20. The uptake of (18F-FDG in arterial walls measured by autoradiography positively correlated with macrophage- and pimonidazole-immunopositive areas (r = 0.76, and r = 0.59 respectively; n = 69 for both; p<0.0001. Pimonidazole immunoreactivity was closely localized with the nuclear translocation of hypoxia inducible factor-1α and hexokinase II expression in macrophage-rich neointima. The levels of glycolytic (8 of 8 and pentose phosphate pathway (4 of 6 metabolites increased in LPS and INFγ stimulated macrophages under hypoxic but not normoxic condition. Plasminogen activator inhibitor-1 protein levels in the supernatant were closely

Cadmium exposure and atherosclerotic carotid plaques –Results from the Malmö diet and Cancer study

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Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.se [Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg (Sweden); Barregard, Lars, E-mail: lars.barregard@amm.gu.se [Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE 413 45 Gothenburg (Sweden); Sallsten, Gerd, E-mail: gerd.sallsten@amm.gu.se [Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE 413 45 Gothenburg (Sweden); Forsgard, Niklas, E-mail: niklas.forsgard@vgregion.se [Department of Clinical Chemistry, Sahlgrenska University Hospital, SE-413 45 Gothenburg (Sweden); Östling, Gerd, E-mail: gerd.ostling@med.lu.se [Cardiovascular Epidemiology, Department of Clinical Sciences in Malmö, CRC, Jan Waldenströms gata 35, Skane University Hospital, Malmö, 205 02 Malmö (Sweden); Persson, Margaretha, E-mail: margaretha.persson@med.lu.se [Cardiovascular Epidemiology, Department of Clinical Sciences in Malmö, CRC, Jan Waldenströms gata 35, Skane University Hospital, Malmö, 205 02 Malmö (Sweden); Borné, Yan, E-mail: yan.borne@med.lu.se [Cardiovascular Epidemiology, Department of Clinical Sciences in Malmö, CRC, Jan Waldenströms gata 35, Skane University Hospital, Malmö, 205 02 Malmö (Sweden); and others

2015-01-15

Background: Epidemiological studies indicate that cadmium exposure through diet and smoking is associated with increased risk of cardiovascular disease. There are few data on the relationship between cadmium and plaques, the hallmark of underlying atherosclerotic disease. Objectives: To examine the association between exposure to cadmium and the prevalence and size of atherosclerotic plaques in the carotid artery. Methods: A population sample of 4639 Swedish middle-aged women and men was examined in 1991–1994. Carotid plaque was determined by B-mode ultrasound. Cadmium in blood was analyzed by inductively coupled plasma mass spectrometry. Results: Comparing quartile 4 with quartile 1 of blood cadmium, the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6–2.2) after adjustment for sex and, age; 1.4 (1.1–1.8) after additional adjustment for smoking status; 1.4 (1.1–1.7) after the addition of education level and life style factors; 1.3 (1.03–1.8) after additional adjustment for risk factors and predictors of cardiovascular disease. No effect modification by sex was found in the cadmium-related prevalence of plaques. Similarly, ORs for the prevalence of small and large plaques were after full adjustment 1.4 (1.0–2.1) and 1.4 (0.9–2.0), respectively. The subgroup of never smokers showed no association between cadmium and atherosclerotic plaques. Conclusions: These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans. The role of smoking remains unclear. It may both cause residual confounding and be a source of pro-atherogenic cadmium exposure. - Highlights: • Blood cadmium level is associated with atherosclerotic plaques in the carotid artery. • The results extend previous knowledge of cadmium exposure and clinical events. • The role of smoking remains unclear.

Suppression of Remodeling Behaviors with Arachidonic Acid Modification for Enhanced in vivo Antiatherogenic Efficacies of Lovastatin-loaded Discoidal Recombinant High Density Lipoprotein.

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He, Hongliang; Zhang, Mengyuan; Liu, Lisha; Zhang, Shuangshuang; Liu, Jianping; Zhang, Wenli

2015-10-01

A series of in vitro evaluation in our previous studies had proved that arachidonic acid (AA) modification could suppress the remodeling behaviors of lovastatin-loaded discoidal reconstituted high density lipoprotein (LT-d-rHDL) by restraining the reactivity with lecithin cholesterol acyltransferase (LCAT) for reducing undesired drug leakage. This study focuses on the investigation of AA-modified LT-d-rHDL (AA-LT-d-rHDL) in atherosclerotic New Zealand White (NZW) rabbit models to explore whether AA modification could enhance drug targeting delivery and improve antiatherogenic efficacies in vivo. After pharmacokinetics of AA-LT-d-rHDL modified with different AA amount were investigated in atherosclerotic NZW rabbits, atherosclerotic lesions targeting property was assessed by ex vivo imaging of aortic tree and drug distribution. Furthermore, their antiatherogenic efficacies were elaborately evaluated and compared by typical biochemical indices. With AA modification amount augmenting, circulation time of AA-LT-d-rHDL was prolonged, and drug accumulation in the target locus was increased, eventually the significant appreciation in antiatherogenic efficacies were further supported by lower level of bad cholesterol, decreased atherosclerotic lesions areas and mean intima-media thickness (MIT), markedly attenuated matrix metalloproteinase-9 (MMP-9) protein expression and macrophage infiltration. This proof-of-concept study demonstrated that AA-LT-d-rHDL could enhance drug accumulation in atherosclerotic lesion and impede atherosclerosis progression more effectively.

Visual performance of pigeons following hippocampal lesions.

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Bingman, V P; Hodos, W

1992-11-15

The effect of hippocampal lesions on performance in two psychophysical measures of spatial vision (acuity and size-difference threshold) was examined in 7 pigeons. No difference between the preoperative and postoperative thresholds of the experimental birds was found. The visual performance of pigeons in the psychophysical tasks failed to reveal a role of the hippocampal formation in vision. The results argue strongly that the behavioral deficits found in pigeons with hippocampal lesions when tested in a variety of memory-related spatial tasks is not based on a defect in spatial vision but impaired spatial cognition.

The effect of aging on atherosclerotic plaque inflammation and molecular calcification: A PET CT imaging study

DEFF Research Database (Denmark)

Blomberg, Björn; Thomassen, Anders; Simonsen, Jane Angel

Aim: Aging is an important independent risk factor for the inception and maturation of atherosclerotic plaques. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and molecular calcification. Methods: Thirteen healthy volunteers without traditional......SUV) [Mean SUVAORTA - Mean SUVBLOOD POOL]. Furthermore, the average maximum 18F-NaF cSUV was determined in the coronary arteries. Calculating regression and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18F-FDG avidity. A second order...... polynomial regression established that aging is a strong predictor of the degree of aortic plaque inflammation (R2 = 0.71, F statistic = 11.98, P = 0.002). A linear relationship was observed between aging and molecular calcification. Linear regression established that aging is a predictor of both the degree...

Usefulness of Beta2-Microglobulin as a Predictor of All-Cause and Nonculprit Lesion-Related Cardiovascular Events in Acute Coronary Syndromes (from the PROSPECT Study).

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Möckel, Martin; Muller, Reinhold; Searle, Julia; Slagman, Anna; De Bruyne, Bernard; Serruys, Patrick; Weisz, Giora; Xu, Ke; Holert, Fabian; Müller, Christian; Maehara, Akiko; Stone, Gregg W

2015-10-01

In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, plaque burden, plaque composition, and minimal luminal area were associated with an increased risk of adverse cardiovascular events arising from untreated atherosclerotic lesions (vulnerable plaques) in patients with acute coronary syndromes (ACS). We sought to evaluate the utility of biomarker profiling and clinical risk factors to predict 3-year all-cause and nonculprit lesion-related major adverse cardiac events (MACEs). Of 697 patients who underwent successful percutaneous coronary intervention (PCI) for ACS, an array of 28 baseline biomarkers was analyzed. Median follow-up was 3.4 years. Beta2-microglobulin displayed the strongest predictive power of all variables assessed for all-cause and nonculprit lesion-related MACE. In a classification and regression tree analysis, patients with beta2-microglobulin >1.92 mg/L had an estimated 28.7% 3-year incidence of all-cause MACE; C-peptide 1.92 mg/L identified a cohort with a 3-year rate of 18.5%, and C-peptide PROSPECT study, beta2-microglobulin strongly predicted all-cause and nonculprit lesion-related MACE within 3 years after PCI in ACS. C-peptide and HDL provided further risk stratification to identify angiographically mild nonculprit lesions prone to future MACE. Copyright © 2015 Elsevier Inc. All rights reserved.

Emotional intelligence and coronary atherosclerosis: exploratory study using the Trait Meta-Mood Scale

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Mariana Suárez-Bagnasco

2013-12-01

Full Text Available Introduction There are no prior studies that assess emotional intelligence in asymptomatic adults with coronary atherosclerosis. Aim The purpose of this study is to explore associations between emotional intelligence in asymptomatic adults with and without coronary atherosclerotic lesions. Design and method Cross-sectional design. The sample consisted of 100 asymptomatic 30 to 80 year-old adults that met the inclusion and exclusion criteria and who underwent coronary multislice computed tomography. Coronary atherosclerosis was shown by 64-channel multislice computed tomography. Emotional intelligence was assessed by applying the Trait Meta-Mood Scale. Results The sample was composed of 73% men and 27% women. Fifty-one percent had coronary atherosclerotic lesions, 78% had scores below the reference values for both Clarity and Repair. Seventy-nine percent had scores above the reference values for Attention. Statistically significant associations were found between the presence of coronary atherosclerotic lesion and: a emotional attention, chi-square: 0.302, p=0.043, b emotional clarity, chi-square: -0.312, p=0.040, b emotional regulation, chi-square: -0.313, p=0.040. Conclusions: People with coronary atherosclerotic lesions showed an excessive tendency to focus on their own feelings and higher levels of rumination, together with lower ability to identify, distinguish and describe their emotions. Likewise, they have lower ability to reduce or eliminate negative emotions and to increase or maintain the intensity of positive emotions.

Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages.

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Lin, Hung-Chih; Lii, Chong-Kuei; Chen, Hui-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Chen, Haw-Wen

2018-01-01

oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent

Periodontal Pathogens and Atherosclerosis: Implications of Inflammation and Oxidative Modification of LDL

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Tomoko Kurita-Ochiai

2014-01-01

Full Text Available Inflammation is well accepted to play a crucial role in the development of atherosclerotic lesions, and recent studies have demonstrated an association between periodontal disease and cardiovascular disease. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, causative agents of destructive chronic inflammation in the periodontium, can accelerate atheroma deposition in animal models. Emerging evidence suggests that vaccination against virulence factors of these pathogens and anti-inflammatory therapy may confer disease resistance. In this review, we focus on the role of inflammatory mechanisms and oxidative modification in the formation and activation of atherosclerotic plaques accelerated by P. gingivalis or A. actinomycetemcomitans in an ApoE-deficient mouse model and high-fat-diet-fed mice. Furthermore, we examine whether mucosal vaccination with a periodontal pathogen or the anti-inflammatory activity of catechins can reduce periodontal pathogen-accelerated atherosclerosis.

X-irradiation-induced nuclear lesions in cultured mammaliam cells: an ultrastructural analysis

International Nuclear Information System (INIS)

Barham, S.S.; Walters, R.A.

1978-01-01

Electron-dense chromatin aggregates, hereafter referred to as lesions, have been characterized morphologically within interphase nuclei of Chinese hamster cells (line CHO) after a single acute exposure to 400, 800, 1200, or 2000 rad of x irradiation. At all doses studied, lesions were observed only after termination of radiation-induced division delay. Cell profiles were scored by electron microscopy for the presence or absence of nuclear lesions at various times after irradiation. The mitotic fraction from each irradiated population was also scored for each sample by light and electron microscopy. From these data and from simultaneous cell-density counts for each sample, it is apparent that postirradiation cell division is a prerequisite to formation of interphase nuclear lesions. Irradiated cell populations blocked in mitosis by Colcemid beyond the normal period of postirradiation division-delay failed to display nuclear lesions until after Colcemid was removed and cell division was completed. Enzyme digestions of isolated nuclei from irradiated cells with DNase I, RNase A, and Pronase suggest that the nuclear lesions are comprised primarily of chromatin. Nucleolar lesions, as well as various aberrant morphological forms of nucleoli, were also observed in cell populations after the onset of postirradiation cell division during the first 72 hr following exposure to irradiation. Delayed radiation-induced ultrastructural alterations of the nucleus included the formation of cytoplasmic invaginations into the nuclear space and inclusions of membranes within nuclei

Selective expansion of influenza a virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques

NARCIS (Netherlands)

Keller, Tymen T.; van der Meer, Jelger J.; Teeling, Peter; van der Sluijs, Koen; Idu, Mirza M.; Rimmelzwaan, Guus F.; Levi, Marcel; van der Wal, Allard C.; de Boer, Onno J.

2008-01-01

Background and Purpose-Evidence is accumulating that infection with influenza A virus contributes to atherothrombotic disease. Vaccination against influenza decreases the risk of atherosclerotic syndromes, indicating that inflammatory mechanisms may be involved. We tested the hypothesis that

A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

OpenAIRE

Lin, Juan; Li, Hanjie; Yang, Min; Ren, Junming; Huang, Zhe; Han, Felicia; Huang, Jian; Ma, Jianhui; Zhang, Duanwu; Zhang, Zhirong; Wu, Jianfeng; Huang, Deli; Qiao, Muzhen; Jin, Guanghui; Wu, Qiao

2013-01-01

Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP) 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation reveal...

Impact of the cardiovascular system-associated adipose tissue on atherosclerotic pathology.

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Chistiakov, Dimitry A; Grechko, Andrey V; Myasoedova, Veronika A; Melnichenko, Alexandra A; Orekhov, Alexander N

2017-08-01

Cardiac obesity makes an important contribution to the pathogenesis of cardiovascular disease. One of the important pathways of this contribution is the inflammatory process that takes place in the adipose tissue. In this review, we consider the role of the cardiovascular system-associated fat in atherosclerotic cardiovascular pathology and a non-atherosclerotic cause of coronary artery disease, such as atrial fibrillation. Cardiovascular system-associated fat not only serves as the energy store, but also releases adipokines that control local and systemic metabolism, heart/vascular function and vessel tone, and a number of vasodilating and anti-inflammatory substances. Adipokine appears to play an important protective role in cardiovascular system. Under chronic inflammation conditions, the repertoire of signaling molecules secreted by cardiac fat can be altered, leading to a higher amount of pro-inflammatory messengers, vasoconstrictors, profibrotic modulators. This further aggravates cardiovascular inflammation and leads to hypertension, induction of the pathological tissue remodeling and cardiac fibrosis. Contemporary imaging techniques showed that epicardial fat thickness correlates with the visceral fat mass, which is an established risk factor and predictor of cardiovascular disease in obese subjects. However, this correlation is no longer present after adjustment for other covariates. Nevertheless, recent studies showed that pericardial fat volume and epicardial fat thickness can probably serve as a better indicator for atrial fibrillation. Copyright © 2017 Elsevier B.V. All rights reserved.

Fibulin-2 is present in murine vascular lesions and is important for smooth muscle cell migration

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Ström, A.; Olin, A. I.; Aspberg, A.

2006-01-01

/hyaluronan complexes, an ECM network that has been suggested to be important during tissue repair. In this study we have analysed the presence of fibulin-2 in two different models of murine vascular lesions. We have also examined how the fibulin-2/versican network influences SMC migration. Methods: Presence of fibulin......Objective: The vascular extracellular matrix (ECM) can affect smooth muscle cell (SMC) adhesion, migration and proliferation-events that are important during the atherosclerotic process. Fibulin-2 is a member of the ECM protein family of fibulins and has been found to cross-link versican...... and is upregulated during SMC phenotypic modulation in cell culture. Moreover, treatments with peptides that block the interaction between versican and fibulin-2 inhibit SMC migration in vitro. Conclusions: Fibulin-2 can be produced by SMC as a response to injury and may participate in the ECM organisation...

Tissue lesion created by HIFU in continuous scanning mode

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Fan, Tingbo; Liu, Zhenbo; Zhang, Dong

2012-09-01

The lesion formation was numerically and experimentally investigated by the continuous scanning mode. Simulations were presented based on the combination of Khokhlov-Zabolotskaya-Kuznetov (KZK) equation and bio-heat equation. Measurements were performed on porcine liver tissues using a 1.01 MHz single-element focused transducer at various acoustic powers, confirmed the predicted results. Controlling of the peak temperature and lesion by the scanning speed may be exploited for improvement of efficiency in HIFU therapy.

Calcified carotid atherosclerotic plaques on digital panoramic radiographs in patients with Type II diabetes mellitus: A case control study

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Neha Khambete

2015-01-01

Full Text Available Aim: Diabetes mellitus is associated with accelerated carotid artery atherosclerosis and increased risk of stroke. This study was conducted with the objective of determining the prevalence of calcified atherosclerotic plaques on panoramic radiographs of patients with Type II diabetes mellitus. Materials and Methods: Panoramic radiographs of 100 patients (age range 50-84 years with known history of type II diabetes mellitus, visiting the outpatient department were evaluated for the presence of calcified atherosclerotic plaques. Age- and sex-matched controls were evaluated in the same manner. Statistical comparison of prevalence rates was done. Results: The radiographs of diabetics (mean age: 64.45 years revealed that 26% had atheromatous plaques, whereas those of controls (mean age: 65.36 years revealed that 6% had atheromatous plaques. A statistically significant difference (P = 0.01410 was obtained using Yates′ Chi-square test. Conclusion: People with diabetes mellitus had a greater prevalence of calcified atherosclerotic plaques on panoramic radiographs than non-diabetics. Panoramic radiographs of diabetic patients should be screened for the presence of carotid artery atheromatous plaques for timely medical referral of asymptomatic patients and avoiding any further serious consequences like cerebrovascular accidents.

Accumulation of 125I-factor XI in atheroma of rabbit with hereditary hyperlipidemia (WHHL-rabbit)

International Nuclear Information System (INIS)

Komiyama, Y.; Masuda, M.; Murakami, T.; Nishikado, H.; Egawa, H.; Nishimura, T.; Morii, S.; Murata, K.

1989-01-01

We have studied the turnover and accumulation of rabbit factor XI (F.XI) in atherosclerotic lesion in Watanabe-hereditable hyperlipidemic rabbit (WHHL rabbit) to reveal the participation of blood coagulation in atherosclerotic lesion. Rabbit F.XI was iodinated and administered intravenously to WHHL rabbits and Japanese white rabbits. The turnover of 125 I-rabbit F.XI was significantly faster in WHHL rabbits (T1/2 = 2.84 +/- 0.44 days) than in normal rabbits (T1/2 = 4.44 +/- 0.42 days). The thoracic aorta of WHHL rabbit was strongly labelled with 125 I-rabbit F.XI, in sections obtained after 5 days by en-face autoradiography, whereas no radioactivity was detected in normal aorta. By an immunohistochemical study of WHHL rabbit aorta, we confirmed that many F.XI- and fibrin-related compounds existed in the atheroma, whereas albumin did not in these area. These results suggest that the activation of F.XI proceeds on the atherosclerotic lesions of WHHL rabbits

Location of Osteochondritis Dissecans Lesions of the Capitellum.

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Johnson, Christine C; Roberts, Susanne; Mintz, Douglas; Fabricant, Peter D; Hotchkiss, Robert N; Daluiski, Aaron

2018-04-17

The location of capitellar osteochondritis dissecans (OCD) lesions in the sagittal plane guides the surgical approach, and lesion location in the coronal plane influences surgical management. Although most lesions have been reported to occur between 4 o'clock and 4:30 (120° to 135° anterior to the humerus), some lesions are located elsewhere in the capitellum. The primary aim was to define the region of the capitellum affected by OCD lesions using a novel clock-face localization system. We reviewed 104 magnetic resonance imaging examinations diagnosing a nontraumatic capitellar OCD lesion. In the sagittal plane, lesion margins were recorded as degrees on the capitellum and converted into a clock-face format in which 0° corresponds to 12:00 with the forearm facing to the right. The 0° axis (12-o'clock axis) was defined as a line parallel to the anterior humeral line that intersects the capitellum center. The following coronal measurements were recorded: lesion width, capitellar width, and distance between the lateral capitellum and lateral lesion. Two independent observers took measurements. In the sagittal plane, average lesion location was 92° to 150° (3:04-5:00, clock face) and ranged from 52.1° to 249.5° (1:44-8:19, clock face). Average lesion dimensions were 10.7 mm (mediolateral width) and 5.2 mm (anteroposterior depth). Interrater reliability was high (intraclass correlation coefficient = 0.98). Using a magnetic resonance imaging-based clock-face localization system, we found that capitellar OCD lesions affect a broad region of the capitellum in the sagittal plane. The clock-face localization system allows for precise description of capitellar OCD lesion location, which may facilitate intraoperative decision and longitudinal monitoring. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Multimodal nonlinear imaging of atherosclerotic plaques differentiation of triglyceride and cholesterol deposits

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Christian Matthäus

2014-09-01

Full Text Available Cardiovascular diseases in general and atherothrombosis as the most common of its individual disease entities is the leading cause of death in the developed countries. Therefore, visualization and characterization of inner arterial plaque composition is of vital diagnostic interest, especially for the early recognition of vulnerable plaques. Established clinical techniques provide valuable morphological information but cannot deliver information about the chemical composition of individual plaques. Therefore, spectroscopic imaging techniques have recently drawn considerable attention. Based on the spectroscopic properties of the individual plaque components, as for instance different types of lipids, the composition of atherosclerotic plaques can be analyzed qualitatively as well as quantitatively. Here, we compare the feasibility of multimodal nonlinear imaging combining two-photon fluorescence (TPF, coherent anti-Stokes Raman scattering (CARS and second-harmonic generation (SHG microscopy to contrast composition and morphology of lipid deposits against the surrounding matrix of connective tissue with diffraction limited spatial resolution. In this contribution, the spatial distribution of major constituents of the arterial wall and atherosclerotic plaques like elastin, collagen, triglycerides and cholesterol can be simultaneously visualized by a combination of nonlinear imaging methods, providing a powerful label-free complement to standard histopathological methods with great potential for in vivo application.

Immunohistochemical expression of perforin in lichen planus lesions.

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Gaber, Mohamed Abdelwahed; Maraee, Alaa Hassan; Alsheraky, Dalia Rifaat; Azeem, Marwa Hussain Abdel

2014-12-01

Lichen planus (LP) is a chronic inflammatory papulosquamous skin disease characterized by epidermal basal cell damage and a particular band-like infiltrate predominantly of T cells in the upper dermis. It is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated by CD8+ cytotoxic T lymphocytes and natural killer cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in LP. Is to study the expression and distribution of perforin in the epidermis and dermis of lesional LP skin. Skin biopsy specimens from lesional skin of 31 patients with LP and 10 healthy persons were analyzed by immunohistochemistry. Significant accumulation of perforin + cells was found in both epidermis and dermis of LP lesions compared with healthy skin. Perforin expression was significantly upregulated in the epidermis of LP lesions. Accumulation of perforin + cells in the epidermis of LP lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.

A CD1d-dependent lipid antagonist to NKT cells ameliorates atherosclerosis in ApoE-/- mice by reducing lesion necrosis and inflammation.

Science.gov (United States)

Li, Yi; Kanellakis, Peter; Hosseini, Hamid; Cao, Anh; Deswaerte, Virginie; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

2016-02-01

Atherosclerosis-related deaths from heart attacks and strokes remain leading causes of global mortality, despite the use of lipid-lowering statins. Thus, there is an urgent need to develop additional therapies. Reports that NKT cells promote atherosclerosis and an NKT cell CD1d-dependent lipid antagonist (DPPE-PEG350, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-350]) reduces allergen-induced inflammation led us to investigate its therapeutic potential in preventing the development and progression of experimental atherosclerosis. DPPE-PEG350 was administered to hyperlipidaemic ApoE(-/-) mice with/without established atherosclerosis. Atherosclerosis and immune cells were assessed in the aortic sinus lesions. Lesion expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) responsible for inflammatory immune cell recruitment as well as mRNA expression of IFNγ and its plasma levels were investigated. Necrotic cores and lesion smooth muscle and collagen contents important in plaque stability were determined as were plasma lipid levels. DPPE-PEG350 reduced atherosclerosis development and delayed progression of established atherosclerosis without affecting plasma lipids. CD4 and CD8 T cells and B cells in atherosclerotic lesions were decreased in DPPE-PEG350-treated mice. Lesion MCP-1 and VCAM-1 protein expression and necrotic core size were reduced without affecting lesion smooth muscle and collagen content. IFNγ and lymphocytes were unaffected by the treatment. The attenuation of progression of established atherosclerosis together with reduced development of atherosclerosis in hyperlipidaemic mice by the NKT antagonist, without affecting NKT cell or other lymphocyte numbers, suggests that targeting lesion inflammation via CD1d-dependent activation of NKT cells using DPPE-PEG350 has a therapeutic potential in treating atherosclerosis. Published on behalf of the European Society of

Analysis of haemodynamic disturbance in the atherosclerotic carotid artery using computational fluid dynamics

International Nuclear Information System (INIS)

Birchall, Daniel; Zaman, Azfar; Hacker, Jacob; Davies, Gavin; Mendelow, David

2006-01-01

Computational fluid dynamics (CFD) provides a means for the quantitative analysis of haemodynamic disturbances in vivo, but most work has used phantoms or idealised geometry. Our purpose was to use CFD to analyse flow in carotid atherosclerosis using patient-specific geometry and flow data. Eight atherosclerotic carotid arteries and one healthy control artery were imaged with magnetic resonance angiography (MRA) and duplex ultrasound, and the data used to construct patient-specific computational models used for CFD and wall shear stress (WSS) analysis. There is a progressive change in three-dimensional (3-D) velocity profile and WSS profile with increasing severity of stenosis, characterised by increasing restriction of areas of low WSS, change in oscillation patterns, and progressive rise in WSS within stenoses and downstream jets. Areas of turbulent, retrograde flow and of low WSS are demonstrated in the lee of the stenoses. This study presents the largest CFD analysis of abnormal haemodynamics at the atheromatous carotid bifurcation using patient-specific data and provides the basis for further investigation of causal links between haemodynamic variables and atherogenesis and formation of unstable plaque. We propose that this provides a means for the prospective assessment of relative stroke risk in patients with carotid atherosclerosis. (orig.)

Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis

NARCIS (Netherlands)

Sluimer, Judith C.; Gasc, Jean-Marie; van Wanroij, Job L.; Kisters, Natasja; Groeneweg, Mathijs; Sollewijn Gelpke, Maarten D.; Cleutjens, Jack P.; van den Akker, Luc H.; Corvol, Pierre; Wouters, Bradly G.; Daemen, Mat J.; Bijnens, Ann-Pascale J.

2008-01-01

We sought to examine the presence of hypoxia in human carotid atherosclerosis and its association with hypoxia-inducible transcription factor (HIF) and intraplaque angiogenesis. Atherosclerotic plaques develop intraplaque angiogenesis, which is a typical feature of hypoxic tissue and expression of

Evaluation of radiotracers for the detection of atherosclerotic vulnerable plaque and myocardial angiogenesis

International Nuclear Information System (INIS)

Dimastromatteo, Julien

2010-01-01

Cardiovascular diseases are the leading cause of mortality worldwide. Coronary events are mainly caused by coronary plaque rupture or erosion. However, at present, there is no noninvasive tool available for the detection of vulnerable plaques. The first part of thesis is about evaluation of new radiotracers for the detection of atherosclerotic vulnerable plaques. 99m Tc-B2702p, 20 derivatives, 99m Tc-VP and 99m Tc-VINP28 were evaluated in an experimental model of atherosclerosis (ApoE-/- mice with left carotid artery ligation). 99m Tc- B2702p1 is a potentially useful radiotracer for the in vivo molecular imaging of VCAM-1 expression in atherosclerotic plaques. Myocardial angiogenesis is an important post infarction phenomenon. Angiogenic therapy improves experimentally cardiac parameters. However, clinical trials using the same therapy are more controversial. At present, clinical imaging tools don't allow us to assess angiogenesis therapy. The second part of thesis is about validation of 99m Tc-RAFT-RGD in the detection of myocardial angiogenesis. 99m Tc-RAFT-RGD allow us to perform noninvasive molecular imaging of myocardial angiogenesis in an experimental model. (author)

Influence of ghrelin gene polymorphisms on hypertension and atherosclerotic disease.

Science.gov (United States)

Berthold, Heiner K; Giannakidou, Eleni; Krone, Wilhelm; Trégouët, David-Alexandre; Gouni-Berthold, Ioanna

2010-02-01

Ghrelin is involved in several metabolic and cardiovascular processes. Recent evidence suggests its involvement in blood pressure regulation and hypertension. The aim of the study was to determine associations of single-nucleotide polymorphisms (SNPs) and haplotypes of the ghrelin gene (GHRL) with hypertension and atherosclerotic disease. Six GHRL SNPs (rs27647, rs26802, rs34911341, rs696217, rs4684677 and a -473G/A (with no assigned rsID)) were investigated in a sample of 1143 hypertensive subjects and 1489 controls of Caucasian origin. Both single-locus and haplotype association analyses were performed. In single-locus analyses, only the non-synonymous rs34911341 was associated with hypertension (odds ratio (OR)=1.95 (95% confidence interval (CI): 1.26-3.02), P=0.003). Six common haplotypes with frequency >1% were inferred from the studied GHRL SNPs, and their frequency distribution was significantly different between hypertensive subjects and controls (chi(2)=12.96 with 5 d.f. (degree of freedom), P=0.024). The effect of rs26802 was found to be significantly (P=0.017) modulated by other GHRL SNPs, as its C allele conferred either an increased risk (OR=1.30 (1.08-1.57), P=0.005) or a decreased risk (OR=0.50 (0.23-1.06), P=0.07) of hypertension according to the two different haplotypes on which it can be found. No association of GHRL SNPs or haplotypes with atherosclerotic disease was observed. In conclusion, we observed statistical evidence for association between GHRL SNPs and risk of hypertension.

Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

International Nuclear Information System (INIS)

Aguilar, E.C.; Jascolka, T.L.; Teixeira, L.G.; Lages, P.C.; Ribeiro, A.C.C.; Vieira, E.L.M.; Peluzio, M.C.G.; Alvarez-Leite, J.I.

2012-01-01

Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr −/− , C57BL/6-background). Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12) or 7% pequi oil (Pequi group, N = 12) for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein) and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units). Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action

Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

Energy Technology Data Exchange (ETDEWEB)

Aguilar, E.C. [Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Jascolka, T.L. [Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Teixeira, L.G.; Lages, P.C.; Ribeiro, A.C.C.; Vieira, E.L.M. [Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Peluzio, M.C.G. [Departamento de Nutrição, Universidade Federal de Viçosa, Viçosa, MG (Brazil); Alvarez-Leite, J.I. [Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

2012-05-11

Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr{sup −/−}, C57BL/6-background). Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12) or 7% pequi oil (Pequi group, N = 12) for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein) and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units). Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action.

Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

Directory of Open Access Journals (Sweden)

E.C. Aguilar

2012-07-01

Full Text Available Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr-/-, C57BL/6-background. Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12 or 7% pequi oil (Pequi group, N = 12 for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units. Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action.

Ultrastructural researches on rabbit myxomatosis. Lymphnodal lesions.

Science.gov (United States)

Marcato, P S; Simoni, P

1977-07-01

Ultrastructural examination of head and neck lymph nodes in rabbits with spontaneous subacute myxomatosis showed fusion of immature reticuloendothelial cells which lead to the formation of polykarocytes. There was no ultrastructural evidence of viral infection of these polykaryocytes. Histiosyncytial lymphadenitis can be considered a specific lesion of myxomatosis.

Lesion progression in post-treatment persistent endodontic lesions.

Science.gov (United States)

Yu, Victoria Soo Hoon; Messer, Harold Henry; Shen, Liang; Yee, Robert; Hsu, Chin-ying Stephen

2012-10-01

Radiographic lesions related to root-filled teeth may persist for long periods after treatment and are considered to indicate failure of initial treatment. Persistent lesions are found in a proportion of cases, but information on lesion progression is lacking. This study examined the incidence of lesion improvement, remaining unchanged, and deterioration among persistent lesions in a group of patients recruited from a university-based clinic and identified potential predictors for lesion progression. Patients of a university clinic with persistent endodontic lesions at least 4 years since treatment and with original treatment radiographs available were recruited with informed consent. Data were obtained by interview and from dental records and clinical and radiographic examinations. Univariate and multivariate statistical analyses were carried out by using SPSS (version 19). One hundred fifty-one persistent lesions were identified in 114 patients. A majority of the lesions (107, 70.9%) received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%) improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since treatment. Potential predictors for lesions that did not improve included recall lesion size, pain on biting at recall examination, history of a postobturation flare-up, and a non-ideal root-filling length (P < .05). Lesions that had persisted for a longer period appeared less likely to be improving (relative risk, 1.038; 95% confidence interval, 1.000-1.077). A specific time interval alone should not be used to conclude that a lesion will not resolve without intervention. This study identified several clinical factors that are associated with deteriorating persistent lesions, which should aid in identifying lesions that require further intervention. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Clinical application of lower extremity CTA and lower extremity perfusion CT as a method of diagnostic for lower extremity atherosclerotic obliterans

Energy Technology Data Exchange (ETDEWEB)

Moon, Il Bong; Dong, Kyung Rae [Dept. Radiological Technology, Gwangju Health University, Gwangju (Korea, Republic of); Goo, Eun Hoe [Dept. Radiological Science, Cheongju University, Cheongju (Korea, Republic of)

2016-11-15

The purpose of this study was to assess clinical application of lower extremity CTA and lower extremity perfusion CT as a method of diagnostic for lower extremity atherosclerotic obliterans. From January to July 2016, 30 patients (mean age, 68) were studied with lower extremity CTA and lower extremity perfusion CT. 128 channel multi-detector row CT scans were acquired with a CT scanner (SOMATOM Definition Flash, Siemens medical solution, Germany) of lower extremity perfusion CT and lower extremity CTA. Acquired images were reconstructed with 3D workstation (Leonardo, Siemens, Germany). Site of lower extremity arterial occlusive and stenosis lesions were detected superficial femoral artery 36.6%, popliteal artery 23.4%, external iliac artery 16.7%, common femoral artery 13.3%, peroneal artery 10%. The mean total DLP comparison of lower extremity perfusion CT and lower extremity CTA, 650 mGy-cm and 675 mGy-cm, respectively. Lower extremity perfusion CT and lower extremity CTA were realized that were never be two examination that were exactly the same legions. Future through the development of lower extremity perfusion CT soft ware programs suggest possible clinical applications.

Evaluation and percutaneous management of atherosclerotic peripheral vascular disease

International Nuclear Information System (INIS)

Widlus, D.M.; Osterman, F.A. Jr.

1989-01-01

Atherosclerotic peripheral vascular disease (PVD) of the lower extremities deprives a person of the ability to exercise to their satisfaction, later of the ability to perform the activities of their daily life, and finally of their legs themselves. Peripheral vascular disease has long been managed by the vascular surgeon utilizing endarterectomy and peripheral arterial bypass. Patient acceptance of nonsurgical, percutaneous procedures such as percutaneous transluminal balloon angioplasty (PTA) is high. Increased utilization of these procedures has led to improved techniques and adjuncts to therapy, as well as more critical review of long-term results. This article will review the evaluation and nonoperative management of PVD, with an emphasis on the newer modalities of management presently being investigated

Biomarkers of atherosclerotic plaque vulnerability and their clinical significance

Directory of Open Access Journals (Sweden)

Ran LIU

2016-09-01

Full Text Available Inflammatory reaction plays a crucial role in the occurence and development of atherosclerosis. Both basic and clinical trials have provided evidence that the expression of inflammatory biomarkers are closely related with the degree of atherosclerosis. Treatment towards inflammatory factors would bring benefit to atherosclerotic patients. This review highlighted the mechanistic rationale and specific therapies targeting traditional and novel inflammatory biomarkers, including C-reactive protein (CRP, interleukin-17 (IL-17, secretory phospholipase A2 (sPLA2, lipoprotein-associated phospholipase A2 (Lp-PLA2, endoglin, chemokine receptor and 5-lipoxygenase (5-LO, so as to review its mechanism of action and treatment prospect. DOI: 10.3969/j.issn.1672-6731.2016.09.004

Assessment of atherosclerotic luminal narrowing of coronary arteries based on morphometrically generated visual guides.

Science.gov (United States)

Barth, Rolf F; Kellough, David A; Allenby, Patricia; Blower, Luke E; Hammond, Scott H; Allenby, Greg M; Buja, L Maximilian

Determination of the degree of stenosis of atherosclerotic coronary arteries is an important part of postmortem examination of the heart, but, unfortunately, estimation of the degree of luminal narrowing can be imprecise and tends to be approximations. Visual guides can be useful to assess this, but earlier attempts to develop such guides did not employ digital technology. Using this approach, we have developed two computer-generated morphometric guides to estimate the degree of luminal narrowing of atherosclerotic coronary arteries. The first is based on symmetric or eccentric circular or crescentic narrowing of the vessel lumen and the second on either slit-like or irregularly shaped narrowing of the vessel lumens. Using the Aperio ScanScope XT at a magnification of 20× we created digital whole-slide images of 20 representative microscopic cross sections of the left anterior descending (LAD) coronary artery, stained with either hematoxylin and eosin (H&E) or Movat's pentachrome stain. These cross sections illustrated a variety of luminal profiles and degrees of stenosis. Three representative types of images were selected and a visual guide was constructed with Adobe Photoshop CS5. Using the "Scale" and "Measurement" tools, we created a series of representations of stenosis with luminal cross sections depicting 20%, 40%, 60%, 70%, 80%, and 90% occlusion of the LAD branch. Four pathologists independently reviewed and scored the degree of atherosclerotic luminal narrowing based on our visual guides. In addition, digital technology was employed to determine the degree of narrowing by measuring the cross-sectional area of the 20 microscopic sections of the vessels, first assuming no narrowing and then comparing this to the percent of narrowing determined by precise measurement. Two of the observers were very experienced general autopsy pathologists, one was a first-year pathology resident on his first rotation on the autopsy service, and the fourth observer was a

All That Swells Is Not A Bruise The Morel-Lavallée Lesion.

Science.gov (United States)

Callahan, Carol L; Eisenman, Justin

2016-01-01

Frequently overlooked, Morel-Lavallée lesions are associated with a closed degloving or shearing mechanism causing a dehiscence of underlying soft tissue with formation of a potential space. This space fills with blood, lymph, and cellular debris, giving the lesion a fluctuant appearance on examination. The potential space associated with larger lesions can be a source for hemorrhage in the appropriate clinical context. However, these lesions are often diagnosed late in their clinical course or are misdiagnosed, leading to long-term complications. Management of this injury typically depends upon the size of the lesion. This article discusses a Morel-Lavallée lesion in an active-duty Servicemember requiring treatment by a plastic surgeon and includes the pathophysiology of Morel-Lavallée lesions, diagnostic strategies, and management pearls. 2016.

Gender, Estrogen, and Obliterative Lesions in the Lung

Directory of Open Access Journals (Sweden)

Hamza Assaggaf

2017-01-01

Full Text Available Gender has been shown to impact the prevalence of several lung diseases such as cancer, asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension (PAH. Controversy over the protective effects of estrogen on the cardiopulmonary system should be of no surprise as clinical trials of hormone replacement therapy have failed to show benefits observed in experimental models. Potential confounders to explain these inconsistent estrogenic effects include the dose, cellular context, and systemic versus local tissue levels of estrogen. Idiopathic PAH is disproportionately found to be up to 4 times more common in females than in males; however, estrogen levels cannot explain why males develop PAH sooner and have poorer survival. Since the sex steroid hormone 17β-estradiol is a mitogen, obliterative processes in the lung such as cell proliferation and migration may impact the growth of pulmonary tissue or vascular cells. We have reviewed evidence for biological differences of sex-specific lung obliterative lesions and highlighted cell context-specific effects of estrogen in the formation of vessel lumen-obliterating lesions. Based on this information, we provide a biological-based mechanism to explain the sex difference in PAH severity as well as propose a mechanism for the formation of obliterative vascular lesions by estrogens.

Microvascular lesions of the true vocal fold.

Science.gov (United States)

Postma, G N; Courey, M S; Ossoff, R H

1998-06-01

Microvascular lesions, also called varices or capillary ectasias, in contrast to vocal fold polyps with telangiectatic vessels, are relatively small lesions arising from the microcirculation of the vocal fold. Varices are most commonly seen in female professional vocalists and may be secondary to repetitive trauma, hormonal variations, or repeated inflammation. Microvascular lesions may either be asymptomatic or cause frank dysphonia by interrupting the normal vibratory pattern, mass, or closure of the vocal folds. They may also lead to vocal fold hemorrhage, scarring, or polyp formation. Laryngovideostroboscopy is the key in determining the functional significance of vocal fold varices. Management of patients with a varix includes medical therapy, speech therapy, and occasionally surgical vaporization. Indications for surgery are recurrent hemorrhage, enlargement of the varix, development of a mass in conjunction with the varix or hemorrhage, and unacceptable dysphonia after maximal medical and speech therapy due to a functionally significant varix.

Insulin-like growth factor I reduces lipid oxidation and foam cell formation via downregulation of 12/15-lipoxygenase.

Science.gov (United States)

Sukhanov, Sergiy; Snarski, Patricia; Vaughn, Charlotte; Lobelle-Rich, Patricia; Kim, Catherine; Higashi, Yusuke; Shai, Shaw-Yung; Delafontaine, Patrice

2015-02-01

We have shown that insulin-like growth factor I (IGF-1) infusion in Apoe(-/-) mice decreased atherosclerotic plaque size and plaque macrophage and lipid content suggesting that IGF-1 suppressed formation of macrophage-derived foam cells. Since 12/15-lipoxygenase (12/15-LOX) plays an important role in OxLDL and foam cell formation, we hypothesized that IGF-1 downregulates 12/15-LOX, thereby suppressing lipid oxidation and foam cell formation. We found that IGF-1 decreased 12/15-LOX plaque immunopositivity and serum OxLDL levels in Apoe(-/-) mice. IGF-1 reduced 12/15-LOX protein and mRNA levels in cultured THP-1 macrophages and IGF-1 also decreased expression of STAT6 transcription factor. IGF-1 reduction in macrophage 12/15-LOX was mediated in part via a PI3 kinase- and STAT6-dependent transcriptional mechanism. IGF-1 suppressed THP-1 macrophage ability to oxidize lipids and form foam cells. IGF-1 downregulated 12/15-LOX in human blood-derived primary macrophages and IGF-1 decreased LDL oxidation induced by these cells. IGF-1 reduced LDL oxidation and formation of foam cells by wild type murine peritoneal macrophages, however these effects were completely blocked in 12/15-LOX-null macrophages suggesting that the ability of IGF-1 to reduce LDL oxidation and foam cells formation is dependent on its ability to downregulate 12/15-LOX. Overall our data demonstrate that IGF-1 reduces lipid oxidation and foam cell formation via downregulation of 12/15-LOX and this mechanism may play a major role in the anti-atherosclerotic effects of IGF-1. Published by Elsevier Ireland Ltd.

Insulin-like Growth Factor I Reduces Lipid Oxidation and Foam Cell Formation via Downregulation of 12/15-lipoxygenase

Science.gov (United States)

Sukhanov, Sergiy; Snarski, Patricia; Vaughn, Charlotte; Lobelle-Rich, Patricia; Kim, Catherine; Higashi, Yusuke; Shai, Shaw-Yung; Delafontaine, Patrice

2014-01-01

Objective We have shown that insulin-like growth factor I (IGF-1) infusion in Apoe−/− mice decreased atherosclerotic plaque size and plaque macrophage and lipid content suggesting that IGF-1 suppressed formation of macrophage-derived foam cells. Since 12/15-lipoxygenase (12/15-LOX) plays an important role in OxLDL and foam cell formation, we hypothesized that IGF-1 downregulates 12/15-LOX, thereby suppressing lipid oxidation and foam cell formation. Approach and Results We found that IGF-1 decreased 12/15-LOX plaque immunopositivity and serum OxLDL levels in Apoe−/− mice. IGF-1 reduced 12/15-LOX protein and mRNA levels in cultured THP-1 macrophages and IGF-1 also decreased expression of STAT6 transcription factor. IGF-1 reduction in macrophage 12/15-LOX was mediated in part via a PI3 kinase- and STAT6-dependent transcriptional mechanism. IGF-1 suppressed THP-1 macrophage ability to oxidize lipids and form foam cells. IGF-1 downregulated 12/15-LOX in human blood-derived primary macrophages and IGF-1 decreased LDL oxidation induced by these cells. IGF-1 reduced LDL oxidation and formation of foam cells by wild type murine peritoneal macrophages, however these effects were completely blocked in 12/15-LOX-null macrophages suggesting that the ability of IGF-1 to reduce LDL oxidation and foam cells formation is dependent on its ability to downregulate 12/15-LOX. Conclusions Overall our data demonstrate that IGF-1 reduces lipid oxidation and foam cell formation via downregulation of 12/15-LOX and this mechanism may play a major role in the anti-atherosclerotic effects of IGF-1. PMID:25549319

Masticator space lesions: MRI and CT findings

International Nuclear Information System (INIS)

Kim, Seung Hoon; Han, Moon Hee; Chang, Kee Kyun; Kim, Kwang Hyun; Song, Jae Uoo; Jo, In Cheol; Yeon, Kyung Mo

1995-01-01

We evaluated the MR and CT findings of the masticator space lesions in order to identify the differences among the malignant and benign tumors and infectious conditions. MR and CT findings in 46 cases with proven masticator space lesions were reviewed retrospectively. We analysed the involvement of masticator muscles, adjacent spaces, orbit and intracranium, homogeneity, necrosis, cystic changes, growth patterns, calcifications, enhancement patterns, MR signal intensity, and CT attenuation. Among the 29 cases of malignant tumors, seven cases were mandibular tumors including four chondrosarcomas, and 22 cases were extramandibular tumors. Malignant tumors of mandibular origin showed large masses with severe bone destruction and epicenter of mandible. Extramandibular malignant tumors showed the epicenter out of the mandible and less severe bone destruction than mandibular tumors. Among the nine benign tumors, four cases were ameloblastomas which showed the well-defined masses and the expansion of the mandible, and four cases were extramandibular tumors which showed well-marginated extramandibular masses with no bone destruction. Among the eight infectious conditions, five cases were mandibular osteomyelitis with or without abscess formations, and the other three cases were infections from adjacent soft tissue or limited to the soft tissue. By careful observations of growth patterns, involvement of the masticator and adjacent spaces, bone changes, and epicenter of the lesions, one can discriminate a mandibular lesion from an extramandibular lesion. With this approach, it is thought to be easier to suggest a diagnosis among a wide spectrum of masticator lesions

Three-dimensional dynamic contrast-enhanced MRI for the accurate, extensive quantification of microvascular permeability in atherosclerotic plaques

NARCIS (Netherlands)

Calcagno, Claudia; Lobatto, Mark E.; Dyvorne, Hadrien; Robson, Philip M.; Millon, Antoine; Senders, Max L.; Lairez, Olivier; Ramachandran, Sarayu; Coolen, Bram F.; Black, Alexandra; Mulder, Willem J. M.; Fayad, Zahi A.

2015-01-01

Atherosclerotic plaques that cause stroke and myocardial infarction are characterized by increased microvascular permeability and inflammation. Dynamic contrast-enhanced MRI (DCE-MRI) has been proposed as a method to quantify vessel wall microvascular permeability in vivo. Until now, most DCE-MRI

Multi-output decision trees for lesion segmentation in multiple sclerosis

Science.gov (United States)

Jog, Amod; Carass, Aaron; Pham, Dzung L.; Prince, Jerry L.

2015-03-01

Multiple Sclerosis (MS) is a disease of the central nervous system in which the protective myelin sheath of the neurons is damaged. MS leads to the formation of lesions, predominantly in the white matter of the brain and the spinal cord. The number and volume of lesions visible in magnetic resonance (MR) imaging (MRI) are important criteria for diagnosing and tracking the progression of MS. Locating and delineating lesions manually requires the tedious and expensive efforts of highly trained raters. In this paper, we propose an automated algorithm to segment lesions in MR images using multi-output decision trees. We evaluated our algorithm on the publicly available MICCAI 2008 MS Lesion Segmentation Challenge training dataset of 20 subjects, and showed improved results in comparison to state-of-the-art methods. We also evaluated our algorithm on an in-house dataset of 49 subjects with a true positive rate of 0.41 and a positive predictive value 0.36.

Combined micro-PIXE and NIR Raman spectroscopic plaque characterisation in a human atherosclerotic aorta sample

International Nuclear Information System (INIS)

Brands, P.J.M.; Poll, S.W.E. van de; Quaedackers, J.A.; Mutsaers, P.H.A.; Puppels, G.J.; Laarse, A. van der; Voigt, M.J.A. de

2001-01-01

Raman spectroscopy can be applied to characterise the chemical composition of an atherosclerotic plaque in vivo. In the near future this technique may become available for use in (coronary) arteries of living patients. For this moment, Raman spectroscopy is applied on artery samples in vitro, to study progression and regression of atherosclerotic plaque. Raman spectroscopy provides chemical information on a molecular basis. In this study, micro-particle induced X-ray emission (micro-PIXE) is applied to provide additional information on the elemental composition of the artery. Furthermore, the combined techniques allow for validation of the structures studied with Raman spectroscopy. This study proves that it is possible to combine and compare both techniques using the same region on the same sample if proper sample preparation is applied. Comparison shows that regions appearing in the Raman spectroscopy results can also be distinguished in micro-PIXE and backscattering spectroscopy (BS) distributions and vice versa. Combining both techniques makes it possible to separate phospholipids from triglycerides. Combined Raman spectroscopy and micro-PIXE/BS is recommended for studying progression and regression of atherosclerosis

The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

DEFF Research Database (Denmark)

McMurray, John; Solomon, Scott; Pieper, Karen

2006-01-01

failure, most treated with an ACE inhibitor). One of the main active controlled trials was confounded by a blood pressure difference between treatments. METHODS: We compared the effects of captopril, valsartan, and their combination on atherosclerotic events in 14,703 patients randomized in the Valsartan...... in Acute Myocardial Infarction Trial (VALIANT). RESULTS: The number of individuals adjudicated as having a fatal or non-fatal MI in the captopril group was 559 (total investigator reported events 798), 587 (796) in the valsartan group, and 554 (756) in the combination group; valsartan versus captopril, p...... = 0.651 (0.965); combination versus captopril, p = 0.187 (0.350). Overall, all atherosclerotic events examined occurred at a similar frequency in the captopril and valsartan groups. CONCLUSIONS: Angiotensin receptor blockers appear to be as effective as ACE inhibitors in reducing atherosclerotic...

Bacteria and bacterial DNA in atherosclerotic plaque and aneurysmal wall biopsies from patients with and without periodontitis

Directory of Open Access Journals (Sweden)

Zahra Armingohar

2014-05-01

Full Text Available Background: Several studies have reported an association between chronic periodontitis (CP and cardiovascular diseases. Detection of periodontopathogens, including red complex bacteria (RCB, in vascular lesions has suggested these bacteria to be involved in the pathogenesis of atherosclerosis and abdominal aortic aneurysms. Objective: In this study, we investigate bacteria and their DNA in vascular biopsies from patients with vascular diseases (VD; i.e. abdominal aortic aneurysms, atherosclerotic carotid, and common femoral arteries, with and without CP. Methods: DNA was extracted from vascular biopsies selected from 40 VD patients: 30 with CP and 10 without CP. The V3-V5 region of the 16S rDNA (V3-V5 was polymerase chain reaction (PCR-amplified, and the amplicons were cloned into Escherichia coli, sequenced, and classified (GenBank and the Human Oral Microbiome database. Species-specific primers were used for the detection of Porphyromonas gingivalis. In addition, 10 randomly selected vascular biopsies from the CP group were subjected to scanning electron microscopy (SEM for visualization of bacteria. Checkerboard DNA–DNA hybridization was performed to assess the presence of RCB in 10 randomly selected subgingival plaque samples from CP patients. Results: A higher load and mean diversity of bacteria were detected in vascular biopsies from VD patients with CP compared to those without CP. Enterobacteriaceae were frequently detected in vascular biopsies together with cultivable, commensal oral, and not-yet-cultured bacterial species. While 70% of the subgingival plaque samples from CP patients showed presence of RCB, only P. gingivalis was detected in one vascular biopsy. Bacterial cells were seen in all 10 vascular biopsies examined by SEM. Conclusions: A higher bacterial load and more diverse colonization were detected in VD lesions of CP patients as compared to patients without CP. This indicated that a multitude of bacterial species both

Study design and rationale of the 'Balloon-Expandable Cobalt Chromium SCUBA Stent versus Self-Expandable COMPLETE-SE Nitinol Stent for the Atherosclerotic ILIAC Arterial Disease (SENS-ILIAC Trial) Trial': study protocol for a randomized controlled trial.

Science.gov (United States)

Choi, Woong Gil; Rha, Seung Woon; Choi, Cheol Ung; Kim, Eung Ju; Oh, Dong Joo; Cho, Yoon Hyung; Park, Sang Ho; Lee, Seung Jin; Hur, Ae Yong; Ko, Young Guk; Park, Sang Min; Kim, Ki Chang; Kim, Joo Han; Kim, Min Woong; Kim, Sang Min; Bae, Jang Ho; Bong, Jung Min; Kang, Won Yu; Seo, Jae Bin; Jung, Woo Yong; Cho, Jang Hyun; Kim, Do Hoi; Ahn, Ji Hoon; Kim, Soo Hyun; Jang, Ji Yong

2016-06-25

The self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease. The purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12 months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound. The SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495 ), registration date: May 8, 2012.

Mechanisms of erosion of atherosclerotic plaques.

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Quillard, Thibaut; Franck, Grégory; Mawson, Thomas; Folco, Eduardo; Libby, Peter

2017-10-01

The present review explores the mechanisms of superficial intimal erosion, a common cause of thrombotic complications of atherosclerosis. Human coronary artery atheroma that give rise to thrombosis because of erosion differ diametrically from those associated with fibrous cap rupture. Eroded lesions characteristically contain few inflammatory cells, abundant extracellular matrix, and neutrophil extracellular traps (NETs). Innate immune mechanisms such as engagement of Toll-like receptor 2 (TLR2) on cultured endothelial cells can impair their viability, attachment, and ability to recover a wound. Hyaluronan fragments may serve as endogenous TLR2 ligands. Mouse experiments demonstrate that flow disturbance in arteries with neointimas tailored to resemble features of human eroded plaques disturbs endothelial cell barrier function, impairs endothelial cell viability, recruits neutrophils, and provokes endothelial cells desquamation, NET formation, and thrombosis in a TLR2-dependent manner. Mechanisms of erosion have received much less attention than those that provoke plaque rupture. Intensive statin treatment changes the characteristic of plaques that render them less susceptible to rupture. Thus, erosion may contribute importantly to the current residual burden of risk. Understanding the mechanisms of erosion may inform the development and deployment of novel therapies to combat the remaining atherothrombotic risk in the statin era.

Effect of rosella extract on development of fatty streaks lesions in female rats

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E. R. Al-Kennany

2010-01-01

Full Text Available This research was conducted to explore the effect of rosella (Hibiscus sabdariffa on female rats on oxidative stress which induced by 0.5% H2O2. Oxidative stress has been investigated via tissue (aorta and heart malonadyaldehyde (MDA as indirect lipid peroxidation index. For atherosclerotic lesions follow up light microscopical technique has been applied. The result elucidate significant reduction in lipid profit parameters namely: low density lipoprotein (LDL-c, triglycerides, very low density lipoprotein (vLDL-c, atherogenic index and significant elevation in high density lipoprotein (HDL-c in few animals treated with H2O2 and rosella extract, parallely, this research illustrate reduction in aorta and heart MDA concentration, concomitant with significant rising in glutathione (GSH level. Histopathologically, this study revealed fatty streaks associated with infiltration of mononuclear inflammatory cells have been detected after 60 days, in animal treated with rosella revealed reduction in lipid vacuoles and proliferation in vascular smooth muscle cells (VSMcs in media toward intimal layers after 40 days from treatment.

Lipocalin-type prostaglandin D synthase is not a biomarker of atherosclerotic manifestations

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Hosbond, Susanne E; Diederichsen, Axel C P; Pedersen, Lise

2014-01-01

tool in the setting of stable coronary artery disease. We set out to investigate if measurement of concentrations of these biomarkers could be used to differentiate between four groups of individuals with different atherosclerotic manifestations. METHODS: A total of 120 individuals from four equal...... gender- and age-matched groups were studied: (i) no previous cardiovascular disease (CVD) and no coronary calcifications [CAC-negative group], (ii) no previous CVD but evidence of severe coronary calcifications [CAC-positive group], (iii) acute coronary syndrome [ACS-group], and (iv) clinical stable...

Angiographic assessment of atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy.

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Çildağ, Mehmet B; Ertuğrul, Bülent M; Köseoğlu, Ömer Fk; Çildağ, Songül; Armstrong, David G

2018-06-01

The aim of this study was to investigate atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy and compare them with patients with diabetic foot without charcot neuro-arthropathy. This retrospective study consists of 78 patients with diabetic foot who had lower extremity angiography with antegrade approach. All patients were classified into two groups; neuro ischemic wounds with charcot neuro-arthropathy (30/78) and without charcot neuro-arthropathy (48/78).Atherosclerotic load at the side of diabetic foot was determined by using the Bollinger angiogram scoring method. Comparison of atherosclerotic load between the two groups was performed. The mean of total and infrapopliteal level angiogram scoring of all patients was 33.3 (standard deviation, sd:±17.2) and 29.3 (sd:±15.6), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds with charcot neuro-arthropathy group was 18.1 (sd:±11.6) and 15.7 (sd:±10.4), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds without charcot neuro-arthropathy group was 42.8 (sd:±12.7) and 37.7 (sd:±12.0), respectively. There was a statistically significant difference between the two groups of mean total and infrapopliteal angiogram scoring (p diabetic foot and chronic charcot neuro-arthropathy is significantly less than in patients with neuroischemic diabetic foot wounds without chronic charcot neuro-arthropathy. Copyright © 2017. Published by Elsevier Taiwan LLC.

Contrast enhancement by differently sized paramagnetic MRI contrast agents in mice with two phenotypes of atherosclerotic plaque

NARCIS (Netherlands)

van Bochove, Glenda S.; Paulis, Leonie E. M.; Segers, Dolf; Mulder, Willem J. M.; Krams, Rob; Nicolay, Klaas; Strijkers, Gustav J.

2011-01-01

Interest in the use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of three differently sized gadolinium-based contrast agents to permeate different mouse plaque phenotypes was evaluated with MRI. A

A comparative study of percutaneous atherectomy for femoropopliteal arterial occlusive disease.

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Gu, Yongquan; Malas, Mahmoud B; Qi, Lixing; Guo, Lianrui; Guo, Jianming; Yu, Hengxi; Tong, Zhu; Gao, Xixiang; Zhang, Jian; Wang, Zhonggao

2017-08-01

SilverHawk™ directional atherectomy has been used to treat more than 300 thousand cases of lower extremity atherosclerotic occlusive disease in the world since it was approved by FDA in 2003. This study aimed to analyze the safety and effectiveness of symptomatic femoral popliteal atherosclerotic disease treated by directional atherectomy (DA). Clinical data of all consecutive patients treated with percutaneous atherectomy utilizing the SilverHawk™ plaque excision was retrospectively analyzed. The anatomic criteria of the atherosclerotic lesions were divided into four types: type I stenosis; type II occlusion; type III in-stent restenosis; type IV stent occlusion. There were 160 patients treated during the study period. Intermittent claudication in 75 patients (47%), rest pain in 55 patients (34.5%) and tissue loss in 30 patients (18.5%). The number of patients was 72, 15, 49 and 24 in type I, II, III and IV lesions, respectively. Technical success rate was 98.6%, 93.3%, 97.9% and 91.7% in type I, II, III and IV lesions, respectively. Debris of intimal plaque was captured by protection device in 92 patients (71.3%). The mean follow-up period was 23.5±10.4 months. Restenosis rate of type I to IV lesions was 21%, 36%, 36% and 40% respectively. Restenosis rate in type I lesion was significantly lower than that in type III and IV lesions (P<0.05). Patients with tissue loss responded to revascularization as follow: type I, 11/13 healed or reduced (84.6%), type II, 3/3 patients improved (100%), type III, 5/6 patients improved (83.3%) and type IV 4/4 healed (100%). In type IV group, four patients had in-stent thrombosis found by postoperative Duplex ultrasonography. They all underwent DA after catheter-directed thrombolysis with good angiographic results. Percutaneous DA is safe and effective for both de-novo atherosclerotic and in-stent stenotic or occlusive lesions. Thrombolysis before plaque excision is recommended in case of in-stenting thrombosis.

Axonal lesion-induced microglial proliferation and microglial cluster formation in the mouse

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Dissing-Olesen, L; Ladeby, R; Nielsen, Helle Hvilsted

2007-01-01

Microglia are innate immune cells and form the first line of defense of the CNS. Proliferation is a key event in the activation of microglia in acute pathology, and has been extensively characterized in rats, but not in mice. In this study we investigated axonal-lesion-induced microglial prolifer...

Perforant path lesioning induces sprouting of CA3-associated fibre systems in mouse hippocampal formation

DEFF Research Database (Denmark)

Drøjdahl, Nina; Hegelund, Iørn V; Poulsen, Frantz R

2002-01-01

mice. We found that lesioning led to translaminar sprouting of Timm stained regio inferior hippocampus (CA3)-associated fibre systems into the denervated termination zones of the CA3 and dentate gyrus, from the adjacent non-denervated stratum radiatum of CA3. Differences were seen in the Timm staining...... pattern of the two strains of mice, while the response to lesioning appeared similar albeit less pronounced than that observed in the rat. We also observed an intensified acetylcholine esterase staining reflective of cholinergic sprouting in the denervated perforant path termination zones, which...... was particularly prominent in areas with sprouting of Timm stained CA3-associated fibres. Finally, we showed that some of the sprouting fibres within the CA3 were myelinated, due to an increased density of silver impregnated myelinated fibres in this region after lesioning. These results show that the basic...

Tissue engineering in the treatment of cartilage lesions

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Jakob Naranđa

2013-11-01

Full Text Available Background: Articular cartilage lesions with the inherent limited healing potential are difficult to treat and thus remain a challenging problem for orthopaedic surgeons. Regenerative treatment techniques, such as autologous chondrocyte implantation (ACI, are promising as a treatment option to restore hyaline-like cartilage tissue in damaged articular surfaces, as opposed to the traditional reparative procedures (e.g. bone marrow stimulation – microfracture, which promote a fibrocartilage formation with lower tissue biomechanical properties and poorer clinical results. ACI technique has undergone several advances and is constantly improving. The new concept of cartilage tissue preservation uses tissue-engineering technologies, combining new biomaterials as a scaffold, application of growth factors, use of stem cells, and mechanical stimulation. The recent development of new generations of ACI uses a cartilage-like tissue in a 3-dimensional culture system that is based on the use of biodegradable material which serves as a temporary scaffold for the in vitro growth and subsequent implantation into the cartilage defect. For clinical practice, single stage procedures appear attractive to reduce cost and patient morbidity. Finally, modern concept of tissue engineering facilitates hyaline-like cartilage formation and a permanent treatment of cartilage lesions.Conclusion: The review focuses on innovations in the treatment of cartilage lesions and covers modern concepts of tissue engineering with the use of biomaterials, growth factors, stem cells and bioreactors, and presents options for clinical use.

High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined 18F-FDG PET/MR imaging

International Nuclear Information System (INIS)

Hyafil, Fabien; Schindler, Andreas; Obenhuber, Tilman; Saam, Tobias; Sepp, Dominik; Hoehn, Sabine; Poppert, Holger; Bayer-Karpinska, Anna; Boeckh-Behrens, Tobias; Hacker, Marcus; Nekolla, Stephan G.; Rominger, Axel; Dichgans, Martin; Schwaiger, Markus

2016-01-01

The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and 18 F-fluoro-deoxyglucose positron emission tomography ( 18 F-FDG PET) imaging. Carotid arteries were imaged 150 min after injection of 18 F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections (n = 460) in both carotid arteries. 18 F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections. The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher 18 F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher 18 F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques. Morphological and biological features of high-risk plaques can be detected with 18 F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral to the stroke, suggesting a causal

High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined {sup 18}F-FDG PET/MR imaging

Energy Technology Data Exchange (ETDEWEB)

Hyafil, Fabien [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Bichat University Hospital, Department of Nuclear Medicine, Paris (France); Schindler, Andreas; Obenhuber, Tilman; Saam, Tobias [Ludwig Maximilians University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Sepp, Dominik; Hoehn, Sabine; Poppert, Holger [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Bayer-Karpinska, Anna [Ludwig Maximilians University Hospital Munich, Institute for Stroke and Dementia Research, Munich (Germany); Boeckh-Behrens, Tobias [Technische Universitaet Muenchen, Department of Neuroradiology, Klinikum Rechts der Isar, Munich (Germany); Hacker, Marcus [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Nekolla, Stephan G. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Partner Site Munich Heart Alliance, German Centre for Cardiovascular Research (DZHK), Munich (Germany); Rominger, Axel [Ludwig Maximilians University Hospital Munich, Department of Nuclear Medicine, Munich (Germany); Dichgans, Martin [Technische Universitaet Muenchen, Department of Neurology, Klinikum rechts der Isar, Munich (Germany); Munich Cluster of Systems Neurology (SyNergy), Munich (Germany); Schwaiger, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

2016-02-15

The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and {sup 18}F-fluoro-deoxyglucose positron emission tomography ({sup 18}F-FDG PET) imaging. Carotid arteries were imaged 150 min after injection of {sup 18}F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections (n = 460) in both carotid arteries. {sup 18}F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections. The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher {sup 18}F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher {sup 18}F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques. Morphological and biological features of high-risk plaques can be detected with {sup 18}F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral

Molecular Imaging of Inflammation in Atherosclerosis

Science.gov (United States)

Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

2013-01-01

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

DNA Damage by Ionizing Radiation: Tandem Double Lesions by Charged Particles

Science.gov (United States)

Huo, Winifred M.; Chaban, Galina M.; Wang, Dunyou; Dateo, Christopher E.

2005-01-01

Oxidative damages by ionizing radiation are the source of radiation-induced carcinogenesis, damage to the central nervous system, lowering of the immune response, as well as other radiation-induced damages to human health. Monte Carlo track simulations and kinetic modeling of radiation damages to the DNA employ available molecular and cellular data to simulate the biological effect of high and low LET radiation io the DNA. While the simulations predict single and double strand breaks and base damages, so far all complex lesions are the result of stochastic coincidence from independent processes. Tandem double lesions have not yet been taken into account. Unlike the standard double lesions that are produced by two separate attacks by charged particles or radicals, tandem double lesions are produced by one single attack. The standard double lesions dominate at the high dosage regime. On the other hand, tandem double lesions do not depend on stochastic coincidences and become important at the low dosage regime of particular interest to NASA. Tandem double lesions by hydroxyl radical attack of guanine in isolated DNA have been reported at a dosage of radiation as low as 10 Gy. The formation of two tandem base lesions was found to be linear with the applied doses, a characteristic of tandem lesions. However, tandem double lesions from attack by a charged particle have not been reported.

Moderate beer consumption does not change early or mature atherosclerosis in mice

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Blanco-Vaca Francisco

2004-01-01

Full Text Available Abstract Background Although the consumption of wine in particular has been associated with a lower risk of atherothrombotic cardiovascular disease, systematic reviews differ as to the relative protective effect of beer, wine and spirits. Two previous studies showed that red wine reduces fatty streak formation (early atherosclerosis but not mature atherosclerosis in apolipoprotein (apo E-deficient (apoE-/- mice. Aim of the study To determine whether a moderate beer intake would affect early and mature atherosclerotic lesion formation using control C57BL/6 and apoE-/- mice, respectively, as models. Methods Control C57BL/6 and apoE-/- mice were randomized to receive either water, ethanol, mild beer, dark beer or ethanol-free beer. The level of beer was designed to approximate the alcohol intake currently believed to be beneficial in reducing human vascular risk. Control C57BL/6 mice were fed a Western diet for 24 weeks, and apoE-/- mice a chow diet for 12 weeks. At the end of the trial period, mice were euthanized and atherosclerotic lesions quantified. Plasma lipid concentrations were also measured. Results The amount of atherosclerosis and average number of lesions in the proximal aortic region did not differ among groups in control C57BL/6 mice (p = 0.32 and p = 0.29, respectively and apoE-/- mice (p = 0.19 and p = 0.59, respectively. No consistent differences were observed in plasma lipid and lipoprotein concentrations among water, ethanol and beer groups. Conclusions Moderate beer consumption does not change the development of early or mature atherosclerosis in mice. Our findings do not support the hypothesis of an anti-atherogenic effect of beer. Other potential protective actions of moderate beer consumption such as plaque stabilization, a reduction in plaque intrinsic thrombogenicity, or a reduction in the systemic propensity to thrombosis, remain to be studied.

Prognosis of non-significant coronary atherosclerotic disease detected by coronary artery tomography

Energy Technology Data Exchange (ETDEWEB)

Barros, Marcio Vinicius Lins; Siqueira, Bruna Pinto; Guimaraes, Carolina Camargos Braichi; Cruz, David Filipe Silva; Guimaraes, Leiziane Assuncao Alves; Lima, Maicom Marcio Perigolo, E-mail: marciovlbarros@gmail.com [Faculdade de Saude e Ecologia Humana, Vespasiano, MG (Brazil); Nunes, Maria do Carmo Pereira [Universidade de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina; Siqueira, Maria Helena Albernaz [Hospital Materdei, Belo Horizonte, MG (Brazil)

2015-07-15

Introduction: Although studies have shown high diagnostic accuracy of coronary tomography (CT) in detecting coronary artery disease (CAD), data on the prognostic value of this method in patients with no significant coronary obstruction are limited. Objective: To evaluate the value of CT in predicting adverse events in patients with suspected CAD and no significant coronary obstruction. Methods: We prospectively evaluated 440 patients between January 2008 and July 2013 by MDCT, diagnosed with no significant obstruction or no atherosclerotic coronary obstruction with an average follow-up of 33 months. The outcomes evaluated were: cardiac death, myocardial infarction, unstable angina associated with hospitalization or coronary artery bypass grafting. Results: Of the 440 patients studied, 295 (67%) were men with mean age 55.9 ± 12.0 years. Non-significant obstruction was found in 152 (35%) of the patients and there were 49 (11%) outcomes. In the multivariate analysis using the Cox regression model, the predictors of clinical outcomes were non-significant obstruction on CT (hazard ratio 3.51; 95% CI 1.73 - 7.8; p <0.01), age and hypertension. Non-significant obstruction on CT was associated with adverse clinical outcomes and survival analysis showed a significant difference (log-rank 24.6; p <0.01) in predicting these outcomes. Conclusion: The detection of non-significant atherosclerotic obstruction by CT was associated with the presence of adverse events in patients with suspected CAD, which may prove useful in the risk stratification of these patients. (author)

Short-term effect of severe exposure to methylmercury on atherosclerotic heart disease and hypertension mortality in Minamata.

Science.gov (United States)

Inoue, Sachiko; Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

2012-02-15

Recent studies suggest potential adverse effects of methylmercury exposure on myocardial infarction and hypertension, although the evidence is still limited. We thus evaluated this association using age-standardized mortality ratios (ASMRs) in Minamata, where severe methylmercury poisoning had occurred. We obtained mortality data from annual vital statistics and demographic statistics from census. We then compared mortality of atherosclerotic heart disease including degenerative heart disease and hypertension in Minamata-city with those in Kumamoto Prefecture, which includes Minamata city, as a control. We estimated ASMRs and 95% confidence intervals (CIs) during the period from 1953 to 1970. ASMRs of atherosclerotic heart disease were continuously decreased during the period from 1953 to 1967. In contrast, the ASMR of hypertension was significantly elevated during the period from 1963 to 1967 (SMR=1.38, CI; 1.06-1.80); but they decreased later. Although dilution is present in this ecological study, our study supports the notion that methylmercury exposure induces hypertension. Copyright © 2011 Elsevier B.V. All rights reserved.

Enhanced base excision repair capacity in carotid atherosclerosis may protect nuclear DNA but not mitochondrial DNA

DEFF Research Database (Denmark)

Skarpengland, Tonje; B. Dahl, Tuva; Skjelland, Mona

2016-01-01

Lesional and systemic oxidative stress has been implicated in the pathogenesis of atherosclerosis, potentially leading to accumulation of DNA base lesions within atherosclerotic plaques. Although base excision repair (BER) is a major pathway counteracting oxidative DNA damage, our knowledge on BER...

Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism

NARCIS (Netherlands)

Helgadottir, Anna; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Holm, Hilma; Patel, Riyaz S.; Gudnason, Thorarinn; Jones, Gregory T.; van Rij, Andre M.; Eapen, Danny J.; Baas, Annette F.; Tregouet, David-Alexandre; Morange, Pierre-Emmanuel; Emmerich, Joseph; Lindblad, Bengt; Gottsater, Anders; Kiemeny, Lambertus A.; Lindholt, Jes S.; Sakalihasan, Natzi; Ferrell, Robert E.; Carey, David J.; Elmore, James R.; Tsao, Philip S.; Grarup, Niels; Jorgensen, Torben; Witte, Daniel R.; Hansen, Torben; Pedersen, Oluf; Pola, Roberto; Gaetani, Eleonora; Magnadottir, Hulda B.; Wijmenga, Cisca; Tromp, Gerard; Ronkainen, Antti; Ruigrok, Ynte M.; Blankensteijn, Jan D.; Mueller, Thomas; Wells, Philip S.; Corral, Javier; Manuel Soria, Jose; Carlos Souto, Juan; Peden, John F.; Jalilzadeh, Shapour; Mayosi, Bongani M.; Keavney, Bernard; Strawbridge, Rona J.; Sabater-Lleal, Maria; Gertow, Karl; Baldassarre, Damiano; Nyyssonen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Tremoli, Elena; de Faire, Ulf; Humphries, Steve E.; Hamsten, Anders; Haraldsdottir, Vilhelmina; Olafsson, Isleifur; Magnusson, Magnus K.; Samani, Nilesh J.; Levey, Allan I.; Markus, Hugh S.; Kostulas, Konstantinos; Dichgans, Martin; Berger, Klaus; Kuhlenbaeumer, Gregor; Ringelstein, E. Bernd; Stoll, Monika; Seedorf, Udo; Rothwell, Peter M.; Powell, Janet T.; Kuivaniemi, Helena; Onundarson, Pall T.; Valdimarsson, Einar; Matthiasson, Stefan E.; Gudbjartsson, Daniel F.; Thorgeirsson, Guomundur; Quyyumi, Arshed A.; Watkins, Hugh; Farrall, Martin; Thorsteinsdottir, Unnur; Stefansson, Kari

2012-01-01

Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with

Temperature distribution in atherosclerotic coronary arteries: influence of plaque geometry and flow (a numerical study)

International Nuclear Information System (INIS)

Have, A G ten; Gijsen, F J H; Wentzel, J J; Slager, C J; Steen, A F W van der

2004-01-01

Intravascular coronary thermography is a method that may detect vulnerable, atherosclerotic plaques and is currently evaluated in a clinical setting. Active macrophages or enzymatic heat releasing processes in vulnerable plaques may act as heat sources. To better understand the parameters of influence on thermographic measurements, numerical simulations have been performed on a model of a coronary artery segment containing a heat source. Heat source parameters and flow were varied to study their influence on temperatures at the lumen wall. Maximal temperature differences at the lumen wall increased when the source volume increased and they differ with the source geometry. The simulations showed that blood flow acts as a coolant to the lumen wall. Blood flow decreased maximal temperatures depending on the source geometry, source volume and the maximal flow velocity. Influence of flow was highest for circumferentially extended sources, up to a factor 3.7, and lowest for longitudinally extended sources, down to a factor 1.9. When cap thickness increased, maximal temperatures decreased and the influence of flow increased. This study shows that correct interpretation of intravascular thermographic measurements requires data on the flow and on the morphologic characteristics of the atherosclerotic plaque

Optimization of dual-wavelength intravascular photoacoustic imaging of atherosclerotic plaques using Monte Carlo optical modeling

Science.gov (United States)

Dana, Nicholas; Sowers, Timothy; Karpiouk, Andrei; Vanderlaan, Donald; Emelianov, Stanislav

2017-10-01

Coronary heart disease (the presence of coronary atherosclerotic plaques) is a significant health problem in the industrialized world. A clinical method to accurately visualize and characterize atherosclerotic plaques is needed. Intravascular photoacoustic (IVPA) imaging is being developed to fill this role, but questions remain regarding optimal imaging wavelengths. We utilized a Monte Carlo optical model to simulate IVPA excitation in coronary tissues, identifying optimal wavelengths for plaque characterization. Near-infrared wavelengths (≤1800 nm) were simulated, and single- and dual-wavelength data were analyzed for accuracy of plaque characterization. Results indicate light penetration is best in the range of 1050 to 1370 nm, where 5% residual fluence can be achieved at clinically relevant depths of ≥2 mm in arteries. Across the arterial wall, fluence may vary by over 10-fold, confounding plaque characterization. For single-wavelength results, plaque segmentation accuracy peaked at 1210 and 1720 nm, though correlation was poor (blood, a primary and secondary wavelength near 1210 and 1350 nm, respectively, may offer the best implementation of dual-wavelength IVPA imaging. These findings could guide the development of a cost-effective clinical system by highlighting optimal wavelengths and improving plaque characterization.

Effective risk stratification in patients with moderate cardiovascular risk using albuminuria and atherosclerotic plaques in the carotid arteries

DEFF Research Database (Denmark)

Greve, Sara V; Blicher, Marie K; Sehestedt, Thomas

2015-01-01

, Systematic COronary Risk Evaluation (SCORE), and Framingham risk score (FRS) groups. Subclinical vascular damage was defined as carotid-femoral pulse wave velocity at least 12 m/s, and carotid atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 90th percentile of 0.73/1.06 mg...... risk patients and high-intermediate FRS risk patients with high risk (P = 0.04 and P = 0.001, respectively), whereas elevated carotid-femoral pulse wave velocity did not. Elevated UACR or presence of atherosclerotic plaques reclassified patients from moderate to high SCORE risk [net reclassification...... improvement of 6.4%; P = 0.025), or from high intermediate to high FRS risk (net reclassification improvement 8.8%; P = 0.002). Assuming primary prevention could reduce the relative cardiovascular risk by 24-27%, on the basis of actual levels of blood pressure and cholesterol, one composite endpoint could...

Tofacitinib ameliorates atherosclerosis and reduces foam cell formation in apoE deficient mice.

Science.gov (United States)

Wang, Zaicun; Wang, Shumei; Wang, Zunzhe; Yun, Tiantian; Wang, Chenchen; Wang, Huating

2017-08-19

Atherosclerosis is a chronic inflammatory cardiovascular disease with high mortality worldwide. Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis. However, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of Tofacitinib on atherogenic diet (ATD)-induced atherosclerosis using apolipoprotein E deficient (apoE-/-) mice. Atherosclerosis-prone apoE-/- mice were fed with ATD and treated with or without Tofacitinib through intragastrical administration (10 mg kg -1 day -1 ) for 8 weeks. Our results showed that Tofacitinib did not change plasma lipids, while significantly reduced the levels of plasma pro-inflammatory cytokines IL-6 and TNF-α. It also significantly attenuated atherosclerotic plaque lesion in the aortic root and macrophages contained in plaque as shown with Mac2 immuno-staining. Peritoneal macrophages (PMC) were separated from apoE-/- mice fed with 8-week ATD, and then subjected to inflammation tests. Flow cytometry analysis of F4/80 and CD206 and mRNA levels of M1 and M2 macrophages markers showed that M1 macrophages decreased while M2 macrophages increased in Tofacitinib treated group. Expressions of other inflammatory genes also indicated an anti-inflammatory status in mice treated with Tofacitinib. Ox-LDL was used to induce foam cell formation from PMC in wild type mice, and the results displayed a reduced formation of foam cells and decreased inflammation in mice with Tofacitinib administration (1 μM). The mRNA and protein levels of ATP binding cassette subfamily A member 1 (ABCA1), a key gene involved in cholesterol efflux, remarkably increased, while it was absence of alterations in scavenger receptors expression. Therefore, we demonstrated that Tofacitinib could attenuate atherosclerosis and foam cells formation by

Relative risk for cardiovascular atherosclerotic events after smoking cessation: 6–9 years excess risk in individuals with familial hypercholesterolemia

Directory of Open Access Journals (Sweden)

Kastelein John JP

2006-10-01

Full Text Available Abstract Background Smoking history is often di- or trichotomized into for example "never, ever or current smoking". However, smoking must be treated as a time-dependent covariate when lifetime data is available. In particular, individuals do not smoke at birth, there is usually a wide variation with respect to smoking history, and smoking cessation must also be considered. Methods Therefore we analyzed smoking as a time-dependent risk factor for cardiovascular atherosclerotic events in a cohort of 2400 individuals with familial hypercholesterolemia who were followed from birth until 2004. Excess risk after smoking-cessation was modelled in a Cox regression model with linear and exponential decaying trends. The model with the highest likelihood value was used to estimate the decay of the excess risk of smoking. Results Atherosclerotic events were observed in 779 patients with familial hypercholesterolemia and 1569 individuals had a smoking history. In the model with the highest likelihood value the risk reduction of smoking after cessation follows a linear pattern with time and it appears to take 6 to 9 years before the excess risk is reduced to zero. The risk of atherosclerotic events due to smoking was estimated as 2.1 (95% confidence interval 1.5; 2.9. Conclusion It was concluded that excess risk due to smoking declined linearly after cessation in at least six to nine years.

Comparison of osteoprotegerin to traditional atherosclerotic risk factors and high-sensitivity C-reactive protein for diagnosis of atherosclerosis

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Mogelvang, Rasmus; Pedersen, Sune Holm; Flyvbjerg, Allan

2012-01-01

Atherosclerosis is the main cause of cardiovascular disease, but the extent of atherosclerosis in individual patients is difficult to estimate. A biomarker of the atherosclerotic burden would be very valuable. The aim of the present study was to evaluate the association of plasma osteoprotegerin ...

Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice

DEFF Research Database (Denmark)

Bentzon, Jacob F; Sondergaard, Claus S; Kassem, Mustafa

2007-01-01

BACKGROUND: Signs of preceding episodes of plaque rupture and smooth muscle cell (SMC)-mediated healing are common in atherosclerotic plaques, but the source of the healing SMCs is unknown. Recent studies suggest that activated platelets adhering to sites of injury recruit neointimal SMCs from ci...

The role of food for the formation and prevention of gastrointestinal lesions induced by aspirin in cats.

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Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

2013-10-01

The effects of feeding conditions (fasted or fed) and dietary fiber (DF) in the diet on gastrointestinal (GI) damage induced by aspirin (ASA) were examined in cats. Plain ASA (P-ASA, 20 mg/kg) or one enteric-coated ASA tablet (EC-ASA, containing 100 mg ASA) was administered p.o. once daily for 3 or 7 days just after morning meal, 3 h after the evening meal, or in the morning without a morning meal (fasted). Several types of diet, dry food (DRY, DF: 2.8 %), canned food (CAN, DF: 0.4 %), and diets with added cellulose or pectin were provided twice daily. P-ASA or EC-ASA administered just after feeding of DRY caused marked lesions in the GI tract, although EC-ASA did not produce any lesions in the stomach. GI damage was markedly decreased when ASA was administered 3 h after the evening meal. The induction of lesions by EC-ASA was markedly decreased in cats that ate CAN, but lesions were induced in cats fed CAN with added cellulose (6 %). The addition of pectin (6 %) to the DRY markedly decreased the induction of lesions by EC-ASA. The results indicate that the induction of GI lesions by ASA was highly dependent on the feeding conditions and DF. To minimize the induction of GI damage, it would be better to take ASA 3 h after the evening meal, or after consuming diets that contain low amounts of insoluble DF and high amounts of soluble DF.

Variations of bubble cavitation and temperature elevation during lesion formation by high-intensity focused ultrasound.

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Zhou, Yufeng; Gao, Xiaobin Wilson

2013-08-01

High-intensity focused ultrasound (HIFU) is emerging as an effective therapeutic modality in both thermal ablations for solid tumor/cancer and soft-tissue fragmentation. Mechanical and thermal effects, which play an important role in the HIFU treatment simultaneously, are dependent on the operating parameters and may vary with the progress of therapy. Mechanical erosion in the shape of a "squid," a "dumbbell" lesion with both mechanical and thermal lesions, or a "tadpole" lesion with mechanical erosion at the center and thermal necrosis on the boundary in the transparent gel phantom could be produced correspondingly with the pulse duration of 5-30 ms, which is much longer than histotripsy burst but shorter than the time for tissue boiling, and pulse repetition frequency (PRF) of 0.2-5 Hz. Meanwhile, variations of bubble cavitation (both inertial and stable cavitation) and temperature elevation in the focal region (i.e., z = -2.5, 0, and 2.5 mm) were measured by passive cavitation detection (PCD) and thermocouples during the therapeutic procedure, respectively. Stable cavitation increased with the pulse duration, PRF, and the number of pulses delivered. However, inertial cavitation was found to increase initially and then decrease with long pulse duration and high PRF. Temperature in the pre-focal region is always higher than those at the focal and post-focal position in all tests. Great variations of PCD signals and temperature elevation are due to the generation and persistence of large bubble, which is resistant to collapse and occurs with the increase of pulse duration and PRF. Similar lesion pattern and variations were also observed in ex vivo porcine kidneys. Hyperechoes in the B-mode ultrasound image were comparable to the shape and size of lesions in the dissected tissue. Thermal lesion volume increased with the increase of pulse duration and PRF, but mechanical erosion reached its maximum volume with the pulse duration of 20 ms and PRF of 1�

Combined Directional Atherectomy and Drug-Eluting Balloon Angioplasty for Isolated Popliteal Artery Lesions in Patients With Peripheral Artery Disease.

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Stavroulakis, Konstantinos; Bisdas, Theodosios; Torsello, Giovanni; Stachmann, Arne; Schwindt, Arne

2015-12-01

To evaluate the midterm results of combined directional atherectomy (DA) and drug-eluting balloon (DEB) angioplasty for atherosclerotic lesions of the popliteal artery. In a single-arm, prospective study, 21 patients (mean age 63±16 years; 16 men) with isolated popliteal artery lesions were enrolled and underwent treatment with combined DA and DEB angioplasty under filter protection between October 2009 and February 2014. The majority (18, 86%) presented with lifestyle-limiting intermittent claudication and 3 with critical limb ischemia. Fifteen (71%) target sites were de novo lesions; 4 were occlusions. The main outcome was primary patency; secondary outcomes were technical success, secondary patency, and early and midterm morbidity and mortality. The TurboHawk atherectomy device was used in 15 (71%) patients and the SilverHawk peripheral plaque excision system in the remaining 6 patients. The In.Pact Admiral/Pacific DEB was used in the majority of cases (15, 71%). The technical success rate was 90% (n=19). One flow-limiting dissection was treated with bailout stenting. Complications included a perforation of the popliteal artery and 2 puncture site hematomas; there was no distal embolic event. The mean follow-up was 18±12 months. Two restenoses were retreated successfully. Kaplan-Meier estimates of primary patency at 12 and 18 months were 95% and 90%, respectively; the secondary patency was 100%. One (5%) patient died in follow-up. None of the patients had an amputation. In this prospective single-arm study, the combined therapy of DA and DEB angioplasty for popliteal artery lesions showed promising midterm performance. The combination of DA and DEB may, in highly selected patients, overcome the challenges presented by the mobility of the knee joint. © The Author(s) 2015.

Gene expression and 18FDG uptake in atherosclerotic carotid plaques

DEFF Research Database (Denmark)

Pedersen, Sune Folke; Graebe, Martin; Fisker Hag, Anne Mette

2010-01-01

) and an additional ipsilateral internal carotid artery stenosis of greater than 60% were recruited. FDG uptake in the carotids was determined by PET/computed tomography and expressed as mean and maximal standardized uptake values (SUVmean and SUVmax). The atherosclerotic plaques were subsequently recovered...... by carotid endarterectomy. The gene expression of markers of vulnerability - CD68, IL-18, matrix metalloproteinase 9, cathepsin K, GLUT-1, and hexokinase type II (HK2) - were measured in plaques by quantitative PCR. RESULTS: In a multivariate linear regression model, GLUT-1, CD68, cathepsin K, and HK2 gene...... expression remained in the final model as predictive variables of FDG accumulation calculated as SUVmean (R=0.26, PK, and HK2 gene expression as independent predictive variables of FDG accumulation calculated...

Relationship between aortic valve calcification and the severity of coronary atherosclerotic disease.

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Qian, Juying; Chen, Zhangwei; Ge, Junbo; Ma, Jianying; Chang, Shufu; Fan, Bing; Liu, Xuebo; Ge, Lei

2010-07-01

Aortic valve calcification (AVC), which has been confirmed to be associated with various risk factors of cardiac disease, is common in the elderly and associated with increased cardiovascular mortality. It has been hypothesized that AVC is associated with coronary atherosclerotic disease, and its severity. Between July 2007 and November 2007, a total of 235 patients with chest pain or chest distress were admitted to the authors' institution for coronary angiography. The severity of coronary atherosclerotic disease (CAD) was evaluated by the Gensini score, the number of stenosed vessels, and the prevalence of total occlusion. All patients underwent transthoracic echocardiography to detect AVC. Patients with CAD had a higher prevalence of AVC than those without CAD (44% versus 26%, p = 0.005). Likewise, the prevalence of AVC was significantly higher in patients with a higher Gensini score than in those with a lower score. Patients with AVC had a higher prevalence of CAD, and higher Gensini scores and numbers of stenosed coronary arteries, even after stratification by age (65 years). On multivariable logistic regression analysis for CAD, the odds ratio (OR) of AVC was 2.315 (95% confidence interval (CI): 1.158-4.629, p = 0.018); this value was higher than that for total cholesterol (OR = 1.637, p = 0.008), lipoprotein-a (OR = 1.003, p = 0.015) and fibrinogen (OR = 1.009, p = 0.006), and marginally less than that for male gender (OR = 2.665, p = 0.005). Patients with AVC had a higher prevalence and greater severity of CAD.

Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study.

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Kundel, Vaishnavi; Trivieri, Maria Giovanna; Karakatsanis, Nicolas A; Robson, Phillip M; Mani, Venkatesh; Kizer, Jorge R; Kaplan, Robert; Fayad, Zahi; Shah, Neomi

2018-03-05

Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging - hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer-before and after continuous positive airway pressure (CPAP). Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3-6 months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP. Five patients were recruited as part of a focused project. Mean age was 52 years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBR mean ) and 6.2% (TBR max ) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others). We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

Science.gov (United States)

2013-01-01

Background The features of carotid atherosclerosis in ketosis-onset diabetes have not been investigated. Our aim was to evaluate the prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed Chinese diabetic patients with ketosis but without islet-associated autoantibodies. Methods In total, 423 newly diagnosed Chinese patients with diabetes including 208 ketosis-onset diabetics without islet-associated autoantibodies, 215 non-ketotic type 2 diabetics and 79 control subjects without diabetes were studied. Carotid atherosclerosis was defined as the presence of atherosclerotic plaques in any of the carotid vessel segments. Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on Doppler ultrasound examination. The clinical features of carotid atherosclerotic lesions were analysed, and the risk factors associated with carotid atherosclerosis were evaluated using binary logistic regression in patients with diabetes. Results The prevalence of carotid atherosclerosis was significantly higher in the ketosis-onset diabetic group (30.80%) than in the control group (15.2%, p=0.020) after adjusting for age- and sex-related differences, but no significant difference was observed in comparison to the non-ketotic diabetic group (35.8%, p=0.487). The mean CIMT of the ketosis-onset diabetics (0.70±0.20 mm) was markedly higher than that of the control subjects (0.57±0.08 mm, pketosis-onset and the non-ketotic diabetes, the prevalence of carotid atherosclerosis was markedly increased with age (both pketosis-onset diabetics, the presence of carotid atherosclerosis was significantly associated with age, hypertension, low-density lipoprotein cholesterol and mean CIMT. Conclusions The prevalence and risk of carotid atherosclerosis were significantly higher in the ketosis-onset diabetics than in the control subjects but similar to that in the non-ketotic type 2

Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

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Smeets, Bart; Angelotti, Maria Lucia; Rizzo, Paola; Dijkman, Henry; Lazzeri, Elena; Mooren, Fieke; Ballerini, Lara; Parente, Eliana; Sagrinati, Costanza; Mazzinghi, Benedetta; Ronconi, Elisa; Becherucci, Francesca; Benigni, Ariela; Steenbergen, Eric; Lasagni, Laura; Remuzzi, Giuseppe; Wetzels, Jack; Romagnani, Paola

2009-12-01

Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase-PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133(+)CD24(+)podocalyxin (PDX)(-)nestin(-) renal progenitors, CD133(+)CD24(+)PDX(+)nestin(+) transitional cells, and CD133(-)CD24(-)PDX(+)nestin(+) differentiated podocytes. In addition, TGF-beta induced CD133(+)CD24(+) progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.

Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors

International Nuclear Information System (INIS)

Rozie, S.; Weert, T.T. de; Monye, C. de; Homburg, P.J.; Tanghe, H.L.J.; Lugt, A. van der; Dippel, D.W.J.

2009-01-01

The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic artery. The contribution of different components was measured as the number of voxels within defined ranges of HU values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid artery. The severity of stenosis and PV were moderately correlated. Age and smoking were independently related to PV. Patients with hypercholesterolemia had significantly less lipid and more calcium in their plaques than patients without hypercholesterolemia. Other cardiovascular risk factors were not significantly related to PV or plaque composition. Luminal stenosis of the carotid artery partly reflects the amount of atherosclerotic carotid disease. Plaque volume and plaque composition are associated with cardiovascular risk factors. (orig.)

Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors

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Rozie, S.; Weert, T.T. de; Monye, C. de; Homburg, P.J.; Tanghe, H.L.J.; Lugt, A. van der [Erasmus MC, University Medical Center Rotterdam, Departments of Radiology, Rotterdam (Netherlands); Dippel, D.W.J. [Erasmus MC, University Medical Center Rotterdam, Department of Neurology, PO Box 2040, Rotterdam (Netherlands)

2009-09-15

The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic artery. The contribution of different components was measured as the number of voxels within defined ranges of HU values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid artery. The severity of stenosis and PV were moderately correlated. Age and smoking were independently related to PV. Patients with hypercholesterolemia had significantly less lipid and more calcium in their plaques than patients without hypercholesterolemia. Other cardiovascular risk factors were not significantly related to PV or plaque composition. Luminal stenosis of the carotid artery partly reflects the amount of atherosclerotic carotid disease. Plaque volume and plaque composition are associated with cardiovascular risk factors. (orig.)

The effect of aging on aortic atherosclerotic plaque inflammation and molecular calcification: A FDG and NaF PET CT imaging study

DEFF Research Database (Denmark)

Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

2013-01-01

Objectives: Aging is an important independent determinant of plaque biology. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and calcification metabolism. Methods: Thirteen healthy volunteers without traditional cardiovascular risk factors were...... and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18-FDG and aortic Na-18F avidity. A second order polynomial regression established that aging is a predictor of the degree of aortic plaque inflammation (R = 0.524; F statistic = 4.93; P = 0...... data, a quadratic relationship appears to exist between aging and plaque inflammation. Furthermore, a quadratic relationship was observed between aging and plaque calcification metabolism. In line with these observations, a linear relationship was observed between atherosclerotic plaque inflammation...

[Current perspectives on endodontic treatment of teeth with chronic periapical lesions].

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Canalda Sahli, C

1990-01-01

The author study in this article histopathological aspects of periapical lesions, intra-granulomatous epithelial proliferation phenomenon as pathogenic mechanism of microscopic cystic cavities formation, diagnostic problems of them all, as well as the most actual therapeutic perspectives.

Examining the prevalence and characteristics of abfractionlike cervical lesions in a population of U.S. veterans.

Science.gov (United States)

Piotrowski, B T; Gillette, W B; Hancock, E B

2001-12-01

Abfraction is believed to be caused by biomechanical loading forces. It may be due to flexure and ultimate fatigue of tooth tissues that occur away from the point of occlusal loading. Other possible causes of cervical lesions include toothbrush abrasion and erosion. The purpose of this study was to investigate the characteristics and prevalence of abfraction-like lesions in a population of U.S. veterans. The authors evaluated 103 teeth with noncarious cervical lesions in 32 subjects and characterized them based on the surface on which the lesion was located, history of toothbrush abrasion, size of the lesion, presence of plaque, surface texture, and presence and size of occlusal wear facets. Clinical examination revealed that adjacent control teeth had a significantly lower percentage of surfaces with plaque than did teeth with cervical lesions. Control teeth also had significantly less gingival recession than did affected teeth. Seventy-five percent of subjects reported a history of using a firm toothbrush, and 78.1 percent reported using a brushing technique that is known to cause toothbrush abrasion in the affected area. Affected teeth had neither significantly different occlusal wear facets nor occlusal contacts than control teeth. No significant correlations were found between cervical lesion dimensions and facet area. Toothbrush abrasion is strongly suspected as contributing to the formation of the majority of wedge-shaped lesions in this group of subjects. A small subset of lesions is thought to have resulted from some other phenomenon. Although the presence or contribution of occlusal stresses in the direct formation of these lesions could not be measured directly, the possibility of abfraction could not be eliminated. Because the existence of abfraction could not be ruled out in about 15 percent of the cases, teeth with noncarious, wedge-shaped lesions warrant careful occlusal evaluation, with the possible need for occlusal adjustment or bitesplint therapy

Are Imaging and Lesioning Convergent Methods for Assessing Functional Specialisation? Investigations Using an Artificial Neural Network

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Thomas, Michael S. C.; Purser, Harry R. M.; Tomlinson, Simon; Mareschal, Denis

2012-01-01

This article presents an investigation of the relationship between lesioning and neuroimaging methods of assessing functional specialisation, using synthetic brain imaging (SBI) and lesioning of a connectionist network of past-tense formation. The model comprised two processing "routes": one was a direct route between layers of input and output…

Fiber-optic system for dual-modality imaging of glucose probes 18F-FDG and 6-NBDG in atherosclerotic plaques.

Directory of Open Access Journals (Sweden)

Raiyan T Zaman

Full Text Available Atherosclerosis is a progressive inflammatory condition that underlies coronary artery disease (CAD-the leading cause of death in the United States. Thus, the ultimate goal of this research is to advance our understanding of human CAD by improving the characterization of metabolically active vulnerable plaques within the coronary arteries using a novel catheter-based imaging system. The aims of this study include (1 developing a novel fiber-optic imaging system with a scintillator to detect both 18F and fluorescent glucose probes, and (2 validating the system on ex vivo murine plaques.A novel design implements a flexible fiber-optic catheter consisting of both a radio-luminescence and a fluorescence imaging system to detect radionuclide 18F-fluorodeoxyglucose (18F-FDG and the fluorescent analog 6-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-ylamino-6-Deoxyglucose (6-NBDG, respectively. Murine macrophage-rich atherosclerotic carotid plaques were imaged ex vivo after intravenous delivery of 18F-FDG or 6-NBDG. Confirmatory optical imaging by IVIS-200 and autoradiography were also performed.Our fiber-optic imaging system successfully visualized both 18F-FDG and 6-NBDG probes in atherosclerotic plaques. For 18F-FDG, the ligated left carotid arteries (LCs exhibited 4.9-fold higher radioluminescence signal intensity compared to the non-ligated right carotid arteries (RCs (2.6 × 10(4 ± 1.4 × 10(3 vs. 5.4 × 10(3 ± 1.3 × 10(3 A.U., P = 0.008. Similarly, for 6-NBDG, the ligated LCs emitted 4.3-fold brighter fluorescent signals than the control RCs (1.6 × 10(2 ± 2.7 × 10(1 vs. 3.8 × 10(1 ± 5.9 A.U., P = 0.002. The higher uptake of both 18F-FDG and 6-NBDG in ligated LCs were confirmed with the IVIS-200 system. Autoradiography further verified the higher uptake of 18F-FDG by the LCs.This novel fiber-optic imaging system was sensitive to both radionuclide and fluorescent glucose probes taken up by murine atherosclerotic plaques. In addition, 6-NBDG is a

Anti-atherosclerotic effect of Cynodon dactylon extract on experimentally induced hypercholesterolemia in rats.

Science.gov (United States)

Pashaie, Belal; Hobbenaghi, Rahim; Malekinejad, Hassan

2017-01-01

Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg -1 ), moderate (200 mg kg -1 ) and maximum (400 mg kg -1 ) doses via gavages. The last group received atorvastatin (10 mg kg -1 ) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon -treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.

Aggressive Ewing's sarcoma appearing as a cold lesion on bone scan

International Nuclear Information System (INIS)

Chatti, K.; Guezguez, M.; Maha Ben Fredj, M.; Sfar, R.; Essabbah, H.; Mtaoumi, M.; Chatti, K.

2009-01-01

Ewing's sarcoma classically presents as a hot spot on bone scan as a result of increased vascularity of the tumor and new bone formation. Purpose We report and analyze an uncommon pattern of a 'cold' lesion in Ewing's sarcoma on bone scan and its pathophysiologic significance. Case report A 15-year-old boy complaining of thigh pain. CT scan evoked Ewing's sarcoma or osteitis. MRI evoked chronic osteitis. Scintigraphy showed a fairly intense and heterogeneous uptake on the femoral lesion and no abnormal uptake elsewhere. Biopsy showed none pathologic pattern. Three months later, a second biopsy concluded to Ewing's sarcoma. Bone scan showed a larger lesion with peripheral intense uptake centered by enlarged 'cold' area in the left femoral diaphysis and no evident bone metastasis. The patient underwent chemotherapy and surgery. Three months later, bone scan showed extensive skeletal metastasis. Conclusion Ewing's sarcoma appears usually as an intense lesion on bone scan. Nevertheless, decreased radiopharmaceutical uptake or 'cold' lesion may be seen in aggressive Ewing's sarcoma with lytic tumor, growth of which is very rapid and bony reaction is minimal. (authors)

Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events.

Science.gov (United States)

Go, Alan S; Hsu, Chi-Yuan; Yang, Jingrong; Tan, Thida C; Zheng, Sijie; Ordonez, Juan D; Liu, Kathleen D

2018-05-17

AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge. We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records. Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12). AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge. Copyright © 2018 by the American Society of Nephrology.

Global gene expression profiling displays a network of dysregulated genes in non-atherosclerotic arterial tissue from patients with type 2 diabetes

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Skov Vibe

2012-02-01

Full Text Available Abstract Background Generalized arterial alterations, such as endothelial dysfunction, medial matrix accumulations, and calcifications are associated with type 2 diabetes (T2D. These changes may render the vessel wall more susceptible to injury; however, the molecular characteristics of such diffuse pre-atherosclerotic changes in diabetes are only superficially known. Methods To identify the molecular alterations of the generalized arterial disease in T2D, DNA microarrays were applied to examine gene expression changes in normal-appearing, non-atherosclerotic arterial tissue from 10 diabetic and 11 age-matched non-diabetic men scheduled for a coronary by-pass operation. Gene expression changes were integrated with GO-Elite, GSEA, and Cytoscape to identify significant biological pathways and networks. Results Global pathway analysis revealed differential expression of gene-sets representing matrix metabolism, triglyceride synthesis, inflammation, insulin signaling, and apoptosis. The network analysis showed a significant cluster of dysregulated genes coding for both intra- and extra-cellular proteins associated with vascular cell functions together with genes related to insulin signaling and matrix remodeling. Conclusions Our results identify pathways and networks involved in the diffuse vasculopathy present in non-atherosclerotic arterial tissue in patients with T2D and confirmed previously observed mRNA-alterations. These abnormalities may play a role for the arterial response to injury and putatively for the accelerated atherogenesis among patients with diabetes.

Characteristics of carotid atherosclerotic plaques of chronic lipid apheresis patients as assessed by In Vivo High-Resolution CMR - a comparative analysis

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Grimm Jochen M

2012-11-01

Full Text Available Abstract Background Components of carotid atherosclerotic plaques can reliably be identified and quantified using high resolution in vivo 3-Tesla CMR. It is suspected that lipid apheresis therapy in addition to lowering serum lipid levels also has an influence on development and progression of atherosclerotic plaques. The purpose of this study was to evaluate the influence of chronic lipid apheresis (LA on the composition of atherosclerotic carotid plaques. Methods 32 arteries of 16 patients during chronic LA-therapy with carotid plaques and stenosis of 1–80% were matched according to degree of stenosis with 32 patients, who had recently suffered an ischemic stroke. Of these patients only the asymptomatic carotid artery was analyzed. All patients underwent black-blood 3 T CMR of the carotids using parallel imaging and dedicated surface coils. Cardiovascular risk factors were recorded. Morphology and composition of carotid plaques were evaluated. For statistical evaluation Fisher’s Exact and unpaired t-test were used. A p-value Results Patients in the LA-group were younger (63.5 vs. 73.9. years, p2, p Conclusion Results of this study suggest that, despite a severer risk profile for cardiovascular complications in LA-patients, chronic LA is associated with significantly lower lipid content in carotid plaques compared to plaques of patients without LA with similar degrees of stenosis, which is characteristic of clinically stable plaques.

The correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease

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Yan-Bing Xi

2017-04-01

Full Text Available Objective: To study the correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease. Methods: A total of 80 patients with coronary heart disease who were treated in our hospital between January 2013 and April 2016 were collected as the observation group, and 50 healthy subjects who received medical examination in our hospital during the same period were selected as the normal control group. Serum PDGF and Ang-2 contents of two groups of patients were detected, and the observation group were further divided into the high PDGF group and low PDGF group (n = 40 as well as the high Ang-2 group and low Ang-2 group (n = 40 according to the median of PDGF and Ang-2 contents. Ultrasonic contrast technology was used to assess the atherosclerotic plaque characteristics in patients with coronary heart disease. Results: Serum PDGF and Ang-2 contents of observation group were significantly higher than those of control group; ultrasound parameters P and AUC levels of high PDGF group were higher than those of low PDGF group while Tp and MTT levels were lower than those of low PDGF group; ultrasound parameters P and AUC levels of high Ang-2 group were higher than those of low Ang-2 group while Tp and MTT levels were lower than those of low Ang-2 group. Conclusion: Serum PDGF and Ang-2 contents increase in patients with coronary heart disease and are negatively correlated with the atherosclerotic plaque stability.

Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries

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McArdle, Sara; Chodaczek, Grzegorz; Ray, Nilanjan; Ley, Klaus

2015-02-01

Intravital multiphoton imaging of arteries is technically challenging because the artery expands with every heartbeat, causing severe motion artifacts. To study leukocyte activity in atherosclerosis, we developed the intravital live cell triggered imaging system (ILTIS). This system implements cardiac triggered acquisition as well as frame selection and image registration algorithms to produce stable movies of myeloid cell movement in atherosclerotic arteries in live mice. To minimize tissue damage, no mechanical stabilization is used and the artery is allowed to expand freely. ILTIS performs multicolor high frame-rate two-dimensional imaging and full-thickness three-dimensional imaging of beating arteries in live mice. The external carotid artery and its branches (superior thyroid and ascending pharyngeal arteries) were developed as a surgically accessible and reliable model of atherosclerosis. We use ILTIS to demonstrate Cx3cr1GFP monocytes patrolling the lumen of atherosclerotic arteries. Additionally, we developed a new reporter mouse (Apoe-/-Cx3cr1GFP/+Cd11cYFP) to image GFP+ and GFP+YFP+ macrophages "dancing on the spot" and YFP+ macrophages migrating within intimal plaque. ILTIS will be helpful to answer pertinent open questions in the field, including monocyte recruitment and transmigration, macrophage and dendritic cell activity, and motion of other immune cells.

Effect of radiomodifying agents on the ratios of X-ray-induced lesions in cellular DNA: use in lethal lesion determination

International Nuclear Information System (INIS)

Radford, I.R.

1986-01-01

The effect of three radiomodifying agents, cysteamine, hyperthermia, and hypoxia, on the induction of the major classes of X-ray-induced DNA lesions, was studied using mouse L cells and Chinese hamster V79 cells. The use of filter elution techniques allowed most of these studies to be conducted at X-ray doses within the survival-curve range. Cysteamine was found to protect against DNA single-strand breakage (ssb), DNA base damage, and DNA-protein crosslinkage. Hyperthermia had no effect on the level of DNA ssb or DNA base damage, but in L cells (but not in V79 cells) it increased the level of DNA-protein crosslinkage relative to DNA ssb. Hypoxia protected against DNA ssb, had no significant effect on the level of DNA base damage, and enhanced the level of DNA-protein crosslinkage relative to DNA ssb. These results support the previous suggestion that the X-ray-induced lethal lesion is DNA double-strand breakage. Implications of these findings for the mechanisms of formation of X-ray-induced DNA lesions are also discussed. (author)

Rehardening of caries-like lesions in root surfaces by saliva substitutes.

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Turssi, Cecilia P; Lima, Renata Q V; Faraoni-Romano, Juliana J; Serra, Mônica C

2006-12-01

This study sought to evaluate whether root dentine caries-like lesions could be remineralised by saliva substitutes. Root dentine slabs (3 x 3 x 2 mm) were cut from bovine incisors, ground flat, polished and pre-tested for Knoop microhardness (KHN) at five locations spaced 500 microm apart and 500 microm from the left edge of each sectioned piece. After 60 out of the 100 slabs had been selected based upon their KHN values, specimens were coated with wax except for their outer surface. Specimens were then cycled through a highly cariogenic challenge model to induce caries-like lesions, whose formation was confirmed by KHN measurements located 500 microm from the right edge of the specimen. According to a randomised complete block design, the experimental units (n = 15) were exposed to 1.5 ml of saliva substitutes, based on either mucin (MC) or carboxymethylcellulose (CM), to natural human saliva (HS) or to 100% relative humidity (RH) over 20 days. Remineralisation was verified by KHN measurements located 1000 microm apart from the right edge of the specimen. Analysis of variance indicated a significant (p < 0.0001) difference among the KHN values attained by the carious root dentine after exposure to the remineralising agents. Tukey's test ascertained that remineralisation was greatest with MC, intermediate with CM and least with HS, but rehardening did not reach the pre-caries lesion formation values. Saliva substitutes may provide partial remineralisation to preformed caries-like lesions in root dentine.

C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques

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Pilely, Katrine; Fumagalli, Stefano; Rosbjerg, Anne

2017-01-01

Inflammation is a part of the initial process leading to atherosclerosis and cholesterol crystals (CC), found in atherosclerotic plaques, which are known to induce complement activation. The pentraxins C-reactive protein (CRP), long pentraxin 3 (PTX3), and serum amyloid P component (SAP) are seru...

Targeted folate receptor β fluorescence imaging as a measure of inflammation to estimate vulnerability within human atherosclerotic carotid plaque

NARCIS (Netherlands)

Jager, Nynke A.; Westra, Johanna; van Dam, Gooitzen M.; Teteloshvili, Nato; Tio, Rene A.; Breek, Jan-Cees; Slart, Riemer H. J. A.; Boersma, Hendrikus H.; Low, Phillip S.; Bijl, Marc; Zeebregts, Clark J.

UNLABELLED: The probability of atherosclerotic plaque rupture and its thrombotic sequelae are thought to be increased at sites of macrophage accumulation. Folate receptor β (FR-β) is present on activated macrophages but not on quiescent macrophages or other immune cells. By conjugating the ligand

A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

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Juan Lin

2013-01-01

Full Text Available Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3−/−;Ldlr−/− and RIP3+/+;Ldlr−/− mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3−/− mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.

The relationship of the gene polymorphisms of matrix metalloproteinase-1, -2, -3 and -9 to the progression of coronary atherosclerotic plaque

International Nuclear Information System (INIS)

Hu Jian; Lu Lin; Wu Liqun; Zhang Qi; Ding Feghua; Yang Zhenkun; Zhang Ruiyan; Zhang Jiansheng; Shen Weifeng

2009-01-01

Objective: To evaluate the influence of the gene polymorphisms of matrix metalloproteinase(mmp)-1, -2, -3 and -9 on coronary atherosclerotic plaque progression. Methods: During the period of January 2005-December 2008, 80 patients with coronary heart disease underwent two times coronary angiography at authors' hospital. Based on the angiographic findings, the patients were classified into plaque progression group (n = 31) and plaque non-progression group (n = 49). Coronary atherosclerotic plaque progression was arbitrarily defined as that the minimal lumen diameter (MLD) of coronary artery showed a decrease ≥ 0.4 mm on the second coronary angiography. The detailed history and clinical examination results were collected, including serum concentrations of lipid profiling, fasting glucose and hs-CRP. Genotypings for polymorphic variances of MMP-1 (-1607 G / GG), MMP-2 (-955 A / C), MMP-3 (-1612 5A / 6A ) and MMP-9 (-1562 C/T) were performed by polymerase chain reaction (PCR) and sequencing analysis in two groups. Comparison of the clinical characteristics and polymorphisms between two groups was made to assess their effects on coronary atherosclerotic plaque progression. Results: More female patients and patients with acute coronary syndrome (ACS) were noted in patients with plaque progression compare to those with no progression (41.9% vs. 18.4%, P < 0.05 and 77.4% vs. 46.3%, P < 0.01, respectively). The serum hs-CRP level also significantly increased in group with plaque progression (0.26 ± 0.44 mg / L vs. 0.02 ± 0.14 mg / L, P < 0.01). Multivariable logistic regression analysis revealed that serum hs-CRP concentration and ACS were independent risk factors of coronary atherosclerotic plaque progression (OR: 12.63,95% CI:1.45-110.29, P < 0.05 and OR:2.99,95% CI:1.04-8.63, P < 0.05, respectively). The frequencies of 6A / 6A genotype and 6A allele of MMP-3 promoter at location -1612 were significantly higher in group with plaque progression than that in group with

Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender

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Pereira Thiago MC

2010-08-01

Full Text Available Abstract Background Although advanced age is considered a risk factor for several diseases, the impact of gender on age-associated cardiovascular diseases, such as atherosclerotic processes and valvular diseases, remains not completely clarified. The present study was designed to assess aortic valve morphology and function and vascular damage in elderly using the apolipoprotein E knockout (ApoE KO mouse. Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice. Methods The grade (0 to 4 of aortic regurgitation was evaluated through angiography. In addition, vascular lipid deposition and senescence were evaluated through histochemical analyses in aged male and female ApoE KO mice, and the results were compared to wild-type C57BL/6J (C57 mice. Results Aortic regurgitation was observed in 92% of the male ApoE KO mice and 100% of the male C57 mice. Comparatively, in age-matched female ApoE KO and C57 mice, aortic regurgitation was observed in a proportion of 58% and 53%, respectively. Histological analysis of the aorta showed an outward (positive remodeling in ApoE KO mice (female: 1.86 ± 0.15; male: 1.89 ± 0.68 using C57 groups as reference values. Histochemical evaluation of the aorta showed lipid deposition and vascular senescence only in the ApoE KO group, which were more pronounced in male mice. Conclusion The data show that male gender contributes to the progression of aortic regurgitation and that hypercholesterolemia and male gender additively contribute to the occurrence of lipid deposition and vascular senescence in elderly mice.

Effects of onion extract on endogenous vascular H2S and adrenomedulin in rat atherosclerosis.

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Li, Wei; Tang, Chaoshu; Jin, Hongfang; Du, Junbao

2011-09-01

This study aimed to explore the effect of onion extract on endogenous hydrogen sulfide (H2S) and adrenomedulin (ADM) and on atherosclerotic progression in rats with atherosclerosis (AS). Male Sprague-Dawley rats were randomly divided into control, AS and AS+onion groups. Ultrastructure of aorta and atherosclerotic lesions both in aorta and in coronary artery were detected. Plasma and aortic H2S were detected by using a sulfide- sensitive electrode. Plasma and aortic ADM was determined with radioimmunoassay. Cystathionine-γ-lyase (CSE), calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP1, RAMP2 and RAMP3) mRNA expressions were analysed. Glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and NO synthase (NOS) contents in plasma, SOD1, SOD2 and ICAM-1 expressions in aorta were detected. Rats in the AS group showed marked atherosclerotic lesions both in aorta and in coronary artery but decreased aortic H2S production. Decreased plasma and aortic ADM content, but increased levels of aortic CRLR, RAMP2 and RAMP3 mRNAs were observed. Plasma GSH-PX and SOD were reduced but MDA elevated. Plasma ICAM-1 and NO contents and iNOS activity were increased. Onion extract, however, lessened atherosclerotic lesions and increased endogenous aortic H2S production, but decreased plasma ADM content, aortic ADM content and aortic CRLR, RAMP2 and RAMP3 mRNAs. In addition, it increased plasma GSH-PX level and SOD activities but reduced MDA; it decreased inflammatory response but increased plasma eNOS activity and NO content. Onion extract exerted a marked antiatherogenic effect in association with the up-regulation of the endogenous CSE/H2S pathway but down-regulation of the ADM/CRLR family in atherosclerotic rats.

Frequency and characteristics of dual pathology in patients with lesional epilepsy.

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Cendes, F; Cook, M J; Watson, C; Andermann, F; Fish, D R; Shorvon, S D; Bergin, P; Free, S; Dubeau, F; Arnold, D L

1995-11-01

We studied 167 patients who had identifiable lesions and temporal or extratemporal partial epilepsy. Pathology included neuronal migration disorders (NMDs) (48), low-grade tumors (52), vascular malformations (34), porencephalic cysts (16), and gliotic lesions as a result of cerebral insults early in life (17). MRI volumetric studies using thin (1.5- or 3-mm) coronal images were performed in all patients and in 44 age-matched normal controls. An atrophic hippocampal formation (HF), indicating dual pathology, was present in 25 patients (15%). Abnormal HF volumes were present in those with lesions involving temporal (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy did not influence the presence of HF atrophy. However, febrile seizures in early childhood were more frequently, although not exclusively, found in patients with hippocampal atrophy. The frequency of hippocampal atrophy in our patients with low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be associated with hippocampal atrophy, independent of the distance of the lesion from the HF. In other types of lesions, such as vascular malformations, dual pathology was found when the lesion was close to the HF. A common pathogenic mechanism during pre- or perinatal development may explain the occurrence of concomitant mesial temporal sclerosis and other structural lesions because of either (1) associated developmental abnormalities or (2) predisposition to prolonged febrile convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in atherosclerotic plaque burden and morphology between type 1 and 2 diabetes as assessed by multislice computed tomography

NARCIS (Netherlands)

Djaberi, Roxana; Schuijf, Joanne D.; Boersma, Eric; Kroft, Lucia J. M.; Pereira, Alberto M.; Romijn, Johannes A.; Scholte, Arthur J.; Jukema, J. Wouter; Bax, Jeroen J.

2009-01-01

OBJECTIVE It is unclear whether the coronary atherosclerotic plaque burden is similar in patients with type 1 and type 2 diabetes. By using multislice computed tomography (MSCT), the presence, degree, and morphology of coronary artery disease (CAD) in patients with type 1 and type 2 diabetes were

Functional MRI in Patients with Intracranial Lesions near Language Areas.

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Hakyemez, B; Erdogan, C; Yildirim, N; Bora, I; Bekar, A; Parlak, M

2006-06-30

We aimed to depict Broca's area and Wernicke's area by word generation and sentence formation paradigms in patients with various intracranial lesions adjacent to language areas using functional MRI technique and to evaluate the ability of functional MRI to lateralize the hemispheric dominance for language. Twenty-three right-handed patients were included in this study. Lesions were classified as low-grade glioma (n=8), high-grade glioma (n=9), metastasis (n=1), meningioma (n=1), arteriovenous malformation (n=2) and mesial temporal sclerosis (n=2). We performed blood-oxygenated-level-dependant functional MRI using a 1.5-T unit. Word generation and sentence formation tasks were used to activate language areas. Language areas were defined as Brodmann 44, 45 (Broca's area) and Brodmann 22 area (Wernicke's area). Laterality index was used to show the dominant hemisphere. Two poorly cooperative patients showed no activation and were excluded from the study. Broca's area was localized in 21 patients (100 %). Wernicke's area, on the other hand, could only be localized in eight of the 21 patients (38 %).The left hemisphere was dominant in 86% of patients while atypical language lateralization (right or bilateral) was demonstrated in 14% of the patients. Bilateral activation areas were shown in 10% of those patients while right cerebral hemisphere was dominant in 4% of the patients. Word generation and sentence formation tasks are especially helpful in localizing Broca's area. Wernicke's area could also be demonstrated in some of the cases. Functional MRI can be used as an important and useful means of demonstrating language areas in patients with lesions adjacent to those areas and depicting the hemispheric dominance.

Combined Inhibition of the BMP pathway and the RANK-RANKL axis in a Mixed Lytic/blastic Prostate Cancer Lesion

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Virk, Mandeep S.; Alaee, Farhang; Petrigliano, Frank A.; Sugiyama, Osamu; Chatziioannou, Arion F.; Stout, David; Dougall, William C.; Lieberman, Jay R.

2010-01-01

The purpose of this study was to investigate the influence of combined inhibition of RANKL (receptor activator of nuclear factor kappa-B ligand) and bone morphogenetic protein (BMP) activity in a mixed lytic/blastic prostate cancer lesion in bone. Human prostate cancer cells (C4 2b) were injected into immunocompromised mice using an intratibial injection model to create mixed lytic/blastic lesions. RANK-Fc, a recombinant RANKL antagonist, was injected subcutaneously three times a week (10mg/kg) to inhibit RANKL and subsequent formation, function and survival of osteoclasts. Inhibition of BMP activity was achieved by transducing prostate cancer cells ex vivo with a retroviral vector expressing noggin (retronoggin; RN). There were three treatment groups (RANK-Fc treatment, RN treatment and combined RN and RANK-Fc treatment) and two control groups (untreated control and empty vector control for the RN treatment group). The progression of bone lesion and tumor growth was evaluated using plain radiographs, hind limb tumor size, 18F-Fluorodeoxyglucose and 18F-fluoride micro PET-CT, histology and histomorphometry. Treatment with RANK-Fc alone inhibited osteolysis and transformed a mixed lytic/blastic lesion into an osteoblastic phenotype. Treatment with RN alone inhibited the osteoblastic component in a mixed lytic/blastic lesion and resulted in formation of smaller osteolytic bone lesion with smaller soft tissue size. The animals treated with both RN and RANK-Fc demonstrated delayed development of bone lesions, inhibition of osteolysis, small soft tissue tumors and preservation of bone architecture with less tumor induced new bone formation. This study suggests that combined inhibition of the RANKL and the BMP pathway may be an effective biologic therapy to inhibit the progression of established mixed lytic/blastic prostate cancer lesions in bone. PMID:21073986

Lipoprotein(a in Cardiovascular Diseases

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Michele Malaguarnera

2013-01-01

Full Text Available Lipoprotein(a (Lp(a is an LDL-like molecule consisting of an apolipoprotein B-100 (apo(B-100 particle attached by a disulphide bridge to apo(a. Many observations have pointed out that Lp(a levels may be a risk factor for cardiovascular diseases. Lp(a inhibits the activation of transforming growth factor (TGF and contributes to the growth of arterial atherosclerotic lesions by promoting the proliferation of vascular smooth muscle cells and the migration of smooth muscle cells to endothelial cells. Moreover Lp(a inhibits plasminogen binding to the surfaces of endothelial cells and decreases the activity of fibrin-dependent tissue-type plasminogen activator. Lp(a may act as a proinflammatory mediator that augments the lesion formation in atherosclerotic plaques. Elevated serum Lp(a is an independent predictor of coronary artery disease and myocardial infarction. Furthermore, Lp(a levels should be a marker of restenosis after percutaneous transluminal coronary angioplasty, saphenous vein bypass graft atherosclerosis, and accelerated coronary atherosclerosis of cardiac transplantation. Finally, the possibility that Lp(a may be a risk factor for ischemic stroke has been assessed in several studies. Recent findings suggest that Lp(a-lowering therapy might be beneficial in patients with high Lp(a levels. A future therapeutic approach could include apheresis in high-risk patients in order to reduce major coronary events.

Automated diagnosis of focal liver lesions using bidirectional empirical mode decomposition features.

Science.gov (United States)

Acharya, U Rajendra; Koh, Joel En Wei; Hagiwara, Yuki; Tan, Jen Hong; Gertych, Arkadiusz; Vijayananthan, Anushya; Yaakup, Nur Adura; Abdullah, Basri Johan Jeet; Bin Mohd Fabell, Mohd Kamil; Yeong, Chai Hong

2018-03-01

Liver is the heaviest internal organ of the human body and performs many vital functions. Prolonged cirrhosis and fatty liver disease may lead to the formation of benign or malignant lesions in this organ, and an early and reliable evaluation of these conditions can improve treatment outcomes. Ultrasound imaging is a safe, non-invasive, and cost-effective way of diagnosing liver lesions. However, this technique has limited performance in determining the nature of the lesions. This study initiates a computer-aided diagnosis (CAD) system to aid radiologists in an objective and more reliable interpretation of ultrasound images of liver lesions. In this work, we have employed radon transform and bi-directional empirical mode decomposition (BEMD) to extract features from the focal liver lesions. After which, the extracted features were subjected to particle swarm optimization (PSO) technique for the selection of a set of optimized features for classification. Our automated CAD system can differentiate normal, malignant, and benign liver lesions using machine learning algorithms. It was trained using 78 normal, 26 benign and 36 malignant focal lesions of the liver. The accuracy, sensitivity, and specificity of lesion classification were 92.95%, 90.80%, and 97.44%, respectively. The proposed CAD system is fully automatic as no segmentation of region-of-interest (ROI) is required. Copyright © 2018 Elsevier Ltd. All rights reserved.

TRAF3IP2 mediates atherosclerotic plaque development and vulnerability in ApoE−/− mice

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Prasad, Sakamuri Siva Sankara Vara; Higashi, Yusuke; Sukhanov, Sergiy; Siddesha, Jalahalli M; Delafontaine, Patrice; Siebenlist, Ulrich; Chandrasekar, Bysani

2016-01-01

Background and aims Atherosclerosis is a major cause of heart attack and stroke. Inflammation plays a critical role in the development of atherosclerosis. Since the cytoplasmic adaptor molecule TRAF3IP2 (TRAF3-Interacting Protein 2) plays a causal role in various autoimmune and inflammatory diseases, we hypothesized that TRAF3IP2 mediates atherosclerotic plaque development. Methods TRAF3IP2/ApoE double knockout (DKO) mice were generated by crossing TRAF3IP2−/− and ApoE−/− mice. ApoE−/− mice served as controls. Both DKO and control mice were fed a high-fat diet for 12 weeks. Plasma lipids were measured by ELISA, atherosclerosis by en face analysis of aorta and plaque cross-section measurements at the aortic valve region, plaque necrotic core area, collagen and smooth muscle cell content by histomorphometry, and aortic gene expression by RT-qPCR. Results The plasma lipoprotein profile was not altered by TRAF3IP2 gene deletion in ApoE−/− mice. While total aortic plaque area was decreased in DKO female, but not male mice, the plaque necrotic area was significantly decreased in DKO mice of both genders. Plaque collagen and smooth muscle cell contents were increased significantly in both female and male DKO mice compared to respective controls. Aortic expression of proinflammatory cytokine (Tumor necrosis factor α, TNFα), chemokine (Chemokine (C-X-C motif) Ligand 1, CXCL1) and adhesion molecule (Vascular cell adhesion molecule 1, VCAM1; and Intercellular adhesion molecule 1, ICAM1) gene expression were decreased in both male and female DKO mice. In addition, the male DKO mice showed a markedly reduced expression of extracellular matrix (ECM)-related genes, including TIMP1 (Tissue inhibitor of metalloproteinase 1), RECK (Reversion-Inducing- Cysteine-Rich Protein with Kazal Motifs) and ADAM17 (A Disintegrin And Metalloproteinase 17). Conclusions TRAF3IP2 plays a causal role in atherosclerotic plaque development and vulnerability, possibly by inducing the

Neutrophil to lymphocyte ratio is associated with proximal/middle segment of the LAD lesions in patients with ST segment elevation infarction

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Ozlem Arican Ozluk

2017-01-01

Full Text Available Introduction: Neutrophil to lymphocyte ratio (NLR was revaled to have a close relation with atherosclerotic cardiovascular disease. The relationship between NLR and culprit plaque localization has never been studied. Aim of the study : To evaluate the association between NLR and unstable plaque localization of left anterior descending artery (LAD in anterior miyocardial infarction patients. Material and methods : Patients admitted to our hospital with acute anterior STEMI were included. Fifhy-eight patients who have single-vessel disease at LAD and their hematological parameters were analyzed retrospectively. Proximal segment of LAD lesions were groupped as Group I and mid segment of the LAD lesion groupped as Group II. The groups were compared according to their NLR and other parameters. Results : Between group I (n = 41, mean age 52.5 ±12.7 and group II (n = 17, mean ages 52.0 ±10.8; NLR, were significantly higher in group I compared to the group II (6.9 ±5.6 vs. 3.3 ±2.0, p = 0.01. In group I, left ventricular ejection fraction (LVEF was significantly lower (p = 0.02. In correlation analyzes, NLR was positively correlated with CK MB (r = 0.32, p = 0.01 and negatively correlated with LVEF (r = –0.28, p = 0.03. Conclusions : The present study demonstrated that anterior myocardial infarction patients with high NLR had a greater possibility having proximal culprit lesion on the LAD. Therefore NLR can be used as a useful tool to culprit plaque localization in patients with acute miyocardial infarction patients.

MRI of bone and soft tissue tumors and tumorlike lesions. Differential diagnosis and atlas

Energy Technology Data Exchange (ETDEWEB)

Meyers, S.P. [Rochester Univ., NY (United States). School of Medicine and Dentistry

2008-07-01

The book is devided into three main sections: the introduction presents a detailed overview of magnetic resonance imaging (MRI) of muscoskeletal tumors and tumorlike lesions and includes multiple tables regarding teh WHO classification of bone and soft tissue tumors, their relative frequencies and pertinent immunohistochemical and genetic data. The second part contains 20 tables of differential diagnosis of lesions based on anatomic locations and/or specific MRI features. Pertinent radiographic and CT findings and key clinical data are summarized. The third part contains 77 Atlas chapters organized into a routine format that enables the efficient acquisition of specific information regarding each lesion. For the majority of the Atlas chapters multiple MRI images are provided to demonstrate the range of imaging findings and locations associated with the lesions.

Unilateral hippocampal inactivation or lesion selectively impairs remote contextual fear memory.

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Zhou, Heng; Zhou, Qixin; Xu, Lin

2016-10-01

Contextual fear memory depends on the hippocampus, but the role of unilateral hippocampus in this type of memory remains unclear. Herein, pharmacological inactivation or excitotoxic lesions were used to study the role of unilateral hippocampus in the stages of contextual fear memory. The pharmacological experiments revealed that compared with the control groups, unilateral hippocampal blockade did not impair 1-day recent memory following learning, whereas bilateral hippocampal blockade significantly impaired this memory. The lesion experiments showed that compared with the control groups, the formed contextual fear memory was retained for 7 days and that 30-day remote memory was markedly reduced in unilateral hippocampal lesion groups. These results indicate that an intact bilateral hippocampus is required for the formation of remote memory and that unilateral hippocampus is sufficient for recent contextual fear memory.

Glyoxalase 1 overexpression does not affect atherosclerotic lesion size and severity in ApoE-/- mice with or without diabetes

DEFF Research Database (Denmark)

Hanssen, Nordin M J; Brouwers, Olaf; Gijbels, Marion J

2014-01-01

are higher in rupture-prone plaques. We here investigated whether overexpression of human GLO1 in ApoE(-/-) mice could reduce the development of atherosclerosis. METHODS AND RESULTS: We crossed C57BL/6 ApoE(-/-) mice with C57BL/6 GLO1 overexpressing mice (huGLO1(+/-)) to generate ApoE(-/-) (n = 16) and Apo......E(-/-) huGLO1(+/-) (n = 20) mice. To induce diabetes, we injected a subset with streptozotocin (STZ) to generate diabetic ApoE(-/-) (n = 8) and ApoE(-/-) huGLO1(+/-) (n = 13) mice. All mice were fed chow and sacrificed at 25 weeks of age. The GLO1 activity was three-fold increased in huGLO1(+/-) aorta......, but aortic root lesion size and phenotype did not differ between mice with and without huGLO1(+/-) overexpression. We detected no differences in gene expression in aortic arches, in AGE levels and cytokines, in circulating cells, and endothelial function between ApoE(-/-) mice with and without huGLO1...

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

Science.gov (United States)

Hansen, Peter Riis

2018-01-01

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Emerging applications of nanotechnology for the diagnosis and management of vulnerable atherosclerotic plaques

Science.gov (United States)

Yu, Shann S.; Ortega, Ryan A.; Reagan, Brendan W.; McPherson, John A.; Sung, Hak-Joon; Giorgio, Todd D.

2017-01-01

An estimated 16 million people in the United States have coronary artery disease (CAD), and approximately 325,000 people die annually from cardiac arrest. About two-thirds of unexpected cardiac deaths occur without prior recognition of cardiac disease. A vast majority of these deaths are attributable to the rupture of ‘Vulnerable atherosclerotic plaques’. Clinically, plaque vulnerability is typically assessed through imaging techniques, and ruptured plaques leading to acute myocardial infarction are treated through angioplasty or stenting. Despite significant advances, it is clear that current imaging methods are insufficiently capable for elucidating plaque composition—which is a key determinant of vulnerability. Further, the exciting improvement in the treatment of CAD afforded by stenting procedures has been buffered by significant undesirable host-implant effects, including restenosis and late thrombosis. Nanotechnology has led to some potential solutions to these problems by yielding constructs that interface with plaque cellular components at an unprecedented size scale. By leveraging the innate ability of macrophages to phagocytose nanoparticles, contrast agents can now be targeted to plaque inflammatory activity. Improvements in nano-patterning procedures have now led to increased ability to regenerate tissue isotropy directly on stents, enabling gradual regeneration of normal, physiologic vascular structures. Advancements in immunoassay technologies promise lower costs for biomarker measurements, and in the near future, may enable the addition of routine blood testing to the clinician’s toolbox—decreasing the costs of atherosclerosis-related medical care. These are merely three examples among many stories of how nanotechnology continues to promise advances in the diagnosis and treatment of vulnerable atherosclerotic plaques. PMID:21834059

Identification of chemical components of combustion emissions that affect pro-atherosclerotic vascular responses in mice

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