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Sample records for atherosclerotic plaque formation

  1. High Field Atherosclerotic Plaque MRI

    OpenAIRE

    Yuan, Chun; Wang, Jinnan; Balu, Niranjan

    2012-01-01

    Manifestations of atherosclerotic plaque in different arterial beds range from perfusion deficits to overt ischemia such as stroke and myocardial infarction. Atherosclerotic plaque composition is known to be associated with its propensity to rupture and cause vascular events. MRI of atherosclerotic plaque using clinical 1.5T scanners can detect plaque composition. Plaque MRI at higher field strengths offers both opportunities and challenges to improving the high spatial-resolution and contras...

  2. Salidroside Decreases Atherosclerotic Plaque Formation in Low-Density Lipoprotein Receptor-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Bu-Chun Zhang

    2012-01-01

    Full Text Available Salidroside is isolated from Rhodiola rosea and is one of the main active components in Rhodiola species. The present study was designed to evaluate the effects of Salidroside on atherosclerotic plaque formation in high-fat diet-(HFD- fed female LDL receptor knockout (LDLr-/- mice. LDLr-/- mice fed an atherogenic HFD for 12 weeks were divided into two groups. One group was administered Salidroside (50 mg/kg/oral gavage daily for 8 weeks, while the control group was administered saline. Salidroside treatment reduced serum lipids levels and the plaque area through the arch to the abdominal aorta. Furthermore, Salidroside improved macrophage content and enhanced collagen and smooth muscle cells contents in the aortic sinus. These changes were associated with reduced MCP-1, VCAM-1, and VCAM-1 protein expression in atherosclerotic aortas. All these results suggest that Salidroside decreases atherosclerotic plaques formation via effects on lipid lowering and anti-inflammation in HFD-fed LDLr−/− mice.

  3. miR-143 is involved in endothelial cell dysfunction through suppression of glycolysis and correlated with atherosclerotic plaques formation.

    Science.gov (United States)

    Xu, R-H; Liu, B; Wu, J-D; Yan, Y-Y; Wang, J-N

    2016-10-01

    Atherosclerosis is recognized as a chronic inflammatory disease leading to hardening of the vessel wall and narrowing of arteries. Endothelial cells (ECs) exhibit highly active glycolysis, the dysfunction of which leads to accumulation of lipids in the arterial wall and formation of atherosclerotic plaque. qRT-PCR was performed to compare the deregulated miR-143 between atherosclerotic plaque and normal vessel tissues. The direct target of miR-143 was verified by Western blot and luciferase assay. The metabolic enzymes in atherosclerotic plaque and normal vessel tissues were measured. HUVECs were transfected with miR-143 precursor or control microRNAs, and glucose uptake, lactate production, intracellular ATP, and oxygen consumption were measured. In this study, we report a correlation between up-regulated miR-143, EC dysfunction, and atherosclerotic plaque formation. The glycolysis rate was significantly elevated in ECs, which show relatively low levels of miR-143. Importantly, miR-143 was upregulated in clinical atherosclerotic plaque samples compared with healthy arteries, suggesting that miR-143 might play important roles in the atherosclerotic plaque formation. Moreover, mRNA levels of key enzymes of glycolysis, such as HK2, LDHA, and PKM2 are significantly down-regulated in the atherosclerotic plaque samples. Overexpression of miR-143 in HUVECs suppresses glycolysis through direct targeting of HK2, leading to EC dysfunction. Restoration of HK2 expression rescues glycolysis in miR-143-overexpressing HUVECs. This study provides further insight into the metabolic mechanisms involved in atherosclerotic plaque formation due to microRNAs.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Mechanism of ceroid formation in atherosclerotic plaque: in situ studies using a combination of Raman and fluorescence spectroscopy.

    Science.gov (United States)

    Haka, Abigail S; Kramer, John R; Dasari, Ramachandra R; Fitzmaurice, Maryann

    2011-01-01

    Accumulation of the lipid-protein complex ceroid is a characteristic of atherosclerotic plaque. The mechanism of ceroid formation has been extensively studied, because the complex is postulated to contribute to plaque irreversibility. Despite intensive research, ceroid deposits are defined through their fluorescence and histochemical staining properties, while their composition remains unknown. Using Raman and fluorescence spectral microscopy, we examine the composition of ceroid in situ in aorta and coronary artery plaque. The synergy of these two types of spectroscopy allows for identification of ceroid via its fluorescence signature and elucidation of its chemical composition through the acquisition of a Raman spectrum. In accordance with in vitro predictions, low density lipoprotein (LDL) appears within the deposits primarily in its peroxidized form. The main forms of modified LDL detected in both coronary artery and aortic plaques are peroxidation products from the Fenton reaction and myeloperoxidase-hypochlorite pathway. These two peroxidation products occur in similar concentrations within the deposits and represent ∼40 and 30% of the total LDL (native and peroxidized) in the aorta and coronary artery deposits, respectively. To our knowledge, this study is the first to successfully employ Raman spectroscopy to unravel a metabolic pathway involved in disease pathogenesis: the formation of ceroid in atherosclerotic plaque.

  6. Angiogenesis in the atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Caroline Camaré

    2017-08-01

    Full Text Available Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.

  7. Effect of Quercus infectoria and Rosa damascena on lipid profile and atherosclerotic plaque formation in rabbit model of hyperlipidemia.

    Science.gov (United States)

    Gholamhoseinian, A; Shahouzehi, B; Joukar, S; Iranpoor, M

    2012-01-01

    Hyperlipidemia is the cause of many complications in the human societies. In this study, the effect of methanol extracts of Quercus infectoria (QI) galls and Rosa damascena (RD) Mill flower were studied on lipid profile and atherosclerotic plaques formation in hyperlipidemic rabbits. Thirty-six New Zeland white rabbits randomly divided into 6 groups as control (I), hyperlipidemic (II), hyperlipidemic+QI (III), hyperlipidemic+RD (IV), +Atorvastolin (V) and hyperlipidemic+Orlistat (VI) and were fed with high fat diet (0.5% cholesterol and 16% hydrogenated vegetable oil) for 45 days. At the end of the study period, lipid profile and plaque formation were assessed. Total Cholesterol (TC), Low Density Lipoprotein (LDL) and Triglyceride (TG) levels were significantly increased in hyperlipidemic group compared with control group (p < 0.001). Methanol extract consumption of Quercus infectoria significantly decreased plasma levels of TC, TG and LDL (p < 0.001). It also decreased plaques formation in semi lunar valve and thoracic aorta. Rosa damascena mill flower methanol extract moderately decreased the levels of TC, TG, LDL and plaques formation but it was not significant. HDL levels and weight of animals did not show significant difference among groups. Based on the doses used in this study, our finding indicated that QI but no RD methanol extract has anti atherogenic and hypolipidemic activities.

  8. Review: Mechanical Characterization of Carotid Arteries and Atherosclerotic Plaques

    NARCIS (Netherlands)

    Korte, C.L. de; Fekkes, S.; Nederveen, A.J.; Manniesing, R.; Hansen, H.R.

    2016-01-01

    Cardiovascular disease (CVD) is a leading cause of death and is in the majority of cases due to the formation of atherosclerotic plaques in arteries. Initially, thickening of the inner layer of the arterial wall occurs. Continuation of this process leads to plaque formation. The risk of a plaque to

  9. Resolvin E1 Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation Induced Atherogenesis

    Science.gov (United States)

    Hasturk, Hatice; Abdallah, Rima; Kantarci, Alpdogan; Nguyen, Daniel; Giordano, Nicholas; Hamilton, James; Van Dyke, Thomas E.

    2015-01-01

    Objective Epidemiological and recent clinical studies implicate periodontitis as an independent risk factor for cardiovascular disease. Previously, we demonstrated that rabbits with experimental periodontitis and cholesterol diet exhibit more aortic plaque compared to diet alone. We also showed that a proresolution mediator, Resolvin E1 (RvE1), reverses the experimental periodontitis. Here, we determined whether oral/topical application of RvE1 attenuates aortic atherosclerosis induced by both diet and periodontal inflammation. Approach and Results Thirty-nine rabbits on a 13-week regimen of 0.5% cholesterol diet were included. Periodontitis was induced by P. gingivalis in 24 rabbits and 15 rabbits were placed in no-periodontitis groups. Interventions were no-treatment, vehicle, and RvE1 treatment (4μg/site or 0.4 μg/site) topically applied 3-times/ week. At 13 weeks, both periodontitis and atherosclerosis were quantified. Atherosclerotic plaques were assessed by Sudan IV staining, histology and ex vivo MRI. Serum levels of C-reactive protein (CRP) were evaluated as a measure of systemic inflammation.RvE1, used as an oral/topical agent, significantly diminished atherogenesis and prevented periodontitis (pperiodontal inflammation, oral/topical application of RvE1 resulted in significantly less arterial plaque, a lower intima/media ratio, and decreased inflammatory cell infiltration compared to no-treatment (pperiodontitis and prevents vascular inflammation and atherogenesis in the absence of periodontitis. The inhibition of vascular inflammation with endogenous mediators of resolution of inflammation provides a novel approach in the prevention of atherogenic events. PMID:25792445

  10. Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

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    Eugenio Picano

    2015-05-01

    Full Text Available A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques—such as vascular, transesophageal, and intravascular ultrasound—on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque, iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque, and markedly hyperechoic with shadowing (calcific plaque. Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging

  11. Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome

    NARCIS (Netherlands)

    Peeters, W.; Moll, F.L.; Vink, A.; Spek, P.J. van der; Kleijn, D.P.V. de; Vries, J.-P.P.M. de; Verheijen, J.H.; Newby, A.C.; Pasterkamp, G.

    2011-01-01

    Aims Atherosclerotic plaque rupture and subsequent thrombus formation are the major cause of acute cardiovascular events. Local plaque markers may facilitate detection of the vulnerable plaque and help identify the patient at risk for cardiovascular events. Matrix metalloproteinases (MMPs) are

  12. Magnetic force microscopy of atherosclerotic plaque

    National Research Council Canada - National Science Library

    T A Alexeeva; S V Gorobets; O Yu Gorobets; I V Demianenko; O M Lazarenko

    2014-01-01

    In this work by methods of scanning probe microscopy, namely by atomic force microscopy and magnetic force microscopy the fragments of atherosclerotic plaque section of different nature were investigated...

  13. Stress analysis of fracture of atherosclerotic plaques: crack propagation modeling.

    Science.gov (United States)

    Rezvani-Sharif, Alireza; Tafazzoli-Shadpour, Mohammad; Kazemi-Saleh, Davood; Sotoudeh-Anvari, Maryam

    2017-08-01

    Traditionally, the degree of luminal obstruction has been used to assess the vulnerability of atherosclerotic plaques. However, recent studies have revealed that other factors such as plaque morphology, material properties of lesion components and blood pressure may contribute to the fracture of atherosclerotic plaques. The aim of this study was to investigate the mechanism of fracture of atherosclerotic plaques based on the mechanical stress distribution and fatigue analysis by means of numerical simulation. Realistic models of type V plaques were reconstructed based on histological images. Finite element method was used to determine mechanical stress distribution within the plaque. Assuming that crack propagation initiated at the sites of stress concentration, crack propagation due to pulsatile blood pressure was modeled. Results showed that crack propagation considerably changed the stress field within the plaque and in some cases led to initiation of secondary cracks. The lipid pool stiffness affected the location of crack formation and the rate and direction of crack propagation. Moreover, increasing the mean or pulse pressure decreased the number of cycles to rupture. It is suggested that crack propagation analysis can lead to a better recognition of factors involved in plaque rupture and more accurate determination of vulnerable plaques.

  14. Vaporization of atherosclerotic plaques by spark erosion

    OpenAIRE

    Slager, Cornelis J.; Essed, Catharina E.; Schuurbiers, Johan C.H.; Bom, Nicolaas; Serruys, Patrick W.; Meester, Geert T.

    1985-01-01

    textabstractAn alternative to the laser irradiation of atherosclerotic lesions has been developed. A pulsed electrocardiogram R wave-triggered electrical spark erosion technique is described. Controlled vaporization of fibrous and lipid plaques with minimal thermal side effects was achieved and documented histologically in vitro from 30 atherosclerotic segments of six human aortic autopsy specimens. Craters with a constant area and a depth that varied according to the duration of application ...

  15. [Is regression of atherosclerotic plaque possible?

    Science.gov (United States)

    Páramo, José A; Civeira, Fernando

    As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion ('angiographic paradox'). A number of imaging modalities (vascular ultrasound and virtual histology, MRI, optical coherence tomography, positron tomography, etc.) are used for non-invasive assessment of atherosclerosis; most of them can identify plaque volume and composition beyond lumen stenosis. An 'aggressive' lipid-lowering strategy is able to reduce the plaque burden and the incidence of cardiovascular events; this may be attributable, at least in part, to plaque-stabilizing effects. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Mathematical models for atherosclerotic plaque evolution

    NARCIS (Netherlands)

    Bulelzai, M.A.K.

    2013-01-01

    Atherosclerosis is a disease in which low density lipoproteins (LDL) accumulate in the arterial wall due to an inflammatory response, which is triggered by the oxidation of LDL molecules that are already present in the arterial wall. Progression of atherosclerotic plaques involves many components

  17. Modulography: elasticity imaging of atherosclerotic plaques

    NARCIS (Netherlands)

    R. Baldewsing (Radj)

    2006-01-01

    textabstractModulography is an experimental elasticity imaging method. It has potential to become an all-in-one in vivo tool (a) for detecting vulnerable atherosclerotic coronary plaques, (b) for assessing information related to their rupture-proneness and (c) for imaging their elastic material

  18. Vaporization of atherosclerotic plaques by spark erosion

    NARCIS (Netherlands)

    C.J. Slager (Cornelis); C.E. Essed; J.C.H. Schuurbiers (Johan); N. Bom (Klaas); P.W.J.C. Serruys (Patrick); G.T. Meester (Geert)

    1985-01-01

    textabstractAn alternative to the laser irradiation of atherosclerotic lesions has been developed. A pulsed electrocardiogram R wave-triggered electrical spark erosion technique is described. Controlled vaporization of fibrous and lipid plaques with minimal thermal side effects was achieved and

  19. Neovascularization of the atherosclerotic plaque: interplay between atherosclerotic lesion, adventitia-derived microvessels and perivascular fat

    NARCIS (Netherlands)

    van Hinsbergh, Victor W. M.; Eringa, Etto C.; Daemen, Mat J. A. P.

    2015-01-01

    Neovascularization is a prominent feature in advanced human atherosclerotic plaques. This review surveys recent evidence for and remaining uncertainties regarding a role of neovascularization in atherosclerotic plaque progression. Specific emphasis is given to hypoxia, angiogenesis inhibition, and

  20. Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

    Science.gov (United States)

    Khambata, Rayomand S.; Ghosh, Suborno M.; Rathod, Krishnaraj S.; Thevathasan, Tharssana; Filomena, Federica; Xiao, Qingzhong; Ahluwalia, Amrita

    2017-01-01

    Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO3−) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitrate-fed mice there is reduced systemic leukocyte rolling and adherence, circulating neutrophil numbers, neutrophil CD11b expression, and myeloperoxidase activity compared with wild-type littermates. Moreover, we show in both the ApoE KO mice and using an acute model of inflammation that this effect upon neutrophils results in consequent reductions in inflammatory monocyte expression that is associated with elevations of the antiinflammatory cytokine interleukin (IL)-10. In summary, we demonstrate that inorganic nitrate suppresses acute and chronic inflammation by targeting neutrophil recruitment and that this effect, at least in part, results in consequent reductions in the inflammatory status of atheromatous plaque, and suggest that this effect may have clinical utility in the prophylaxis of inflammatory atherosclerotic disease. PMID:28057862

  1. Ghrelin inhibits atherosclerotic plaque angiogenesis and promotes plaque stability in a rabbit atherosclerotic model.

    Science.gov (United States)

    Wang, Li; Chen, Qingwei; Ke, Dazhi; Li, Guiqiong

    2017-04-01

    Intraplaque angiogenesis associates with the instability of atherosclerotic plaques. In the present study, we investigated the effects of ghrelin on intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis. The rabbits were randomly divided into three groups, namely, the control group, atherosclerotic model group, and ghrelin-treated group, with treatments lasting for 4 weeks. We found that the thickness ratio of the intima to media in rabbits of the ghrelin-treated group was significantly lower than that in rabbits of the atherosclerotic model group. The number of neovessels and the levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) decreased dramatically in rabbits of the ghrelin-treated group compared to those of the atherosclerotic model group. Ghrelin significantly decreased the plaque content of macrophages, matrix metalloproteinase (MMP)-2, and MMP-9, in a rabbit model of atherosclerosis. In addition, the level of the pro-inflammatory factor monocyte chemoattractant protein (MCP)-1 was significantly lower in rabbits of the ghrelin-treated group than in rabbits of the atherosclerotic model group. In summary, ghrelin can inhibit intraplaque angiogenesis and promote plaque stability by down-regulating VEGF and VEGFR2 expression, inhibiting the plaque content of macrophages, and reducing MCP-1 expression at an advanced stage of atherosclerosis in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Both transient and continuous corticosterone excess inhibit atherosclerotic plaque formation in APOE*3-leiden.CETP mice.

    Directory of Open Access Journals (Sweden)

    Hanna E Auvinen

    Full Text Available INTRODUCTION: The role of glucocorticoids in atherosclerosis development is not clearly established. Human studies show a clear association between glucocorticoid excess and cardiovascular disease, whereas most animal models indicate an inhibitory effect of glucocorticoids on atherosclerosis development. These animal models, however, neither reflect long-term glucocorticoid overexposure nor display human-like lipoprotein metabolism. AIM: To investigate the effects of transient and continuous glucocorticoid excess on atherosclerosis development in a mouse model with human-like lipoprotein metabolism upon feeding a Western-type diet. METHODS: Pair-housed female APOE*3-Leiden.CETP (E3L.CETP mice fed a Western-type containing 0.1% cholesterol for 20 weeks were given corticosterone (50 µg/ml for either 5 (transient group or 17 weeks (continuous group, or vehicle (control group in the drinking water. At the end of the study, atherosclerosis severity, lesion area in the aortic root, the number of monocytes adhering to the endothelial wall and macrophage content of the plaque were measured. RESULTS: Corticosterone treatment increased body weight and food intake for the duration of the treatment and increased gonadal and subcutaneous white adipose tissue weight in transient group by +35% and +31%, and in the continuous group by +140% and 110%. Strikingly, both transient and continuous corticosterone treatment decreased total atherosclerotic lesion area by -39% without lowering plasma cholesterol levels. In addition, there was a decrease of -56% in macrophage content of the plaque with continuous corticosterone treatment, and a similar trend was present with the transient treatment. CONCLUSION: Increased corticosterone exposure in mice with human-like lipoprotein metabolism has beneficial, long-lasting effects on atherosclerosis, but negatively affects body fat distribution by promoting fat accumulation in the long-term. This indicates that the increased

  3. Uptake of 11C-choline in mouse atherosclerotic plaques

    DEFF Research Database (Denmark)

    Laitinen, Iina E K; Luoto, Pauliina; Någren, Kjell

    2010-01-01

    The purpose of this study was to explore the feasibility of (11)C-choline in the assessment of the degree of inflammation in atherosclerotic plaques.......The purpose of this study was to explore the feasibility of (11)C-choline in the assessment of the degree of inflammation in atherosclerotic plaques....

  4. Atherosclerotic carotid plaque assessment with multidetector computed tomography angiography

    NARCIS (Netherlands)

    T.T. de Weert (Thomas)

    2009-01-01

    textabstractThis thesis evaluates the role of MDCT angiography in 1) the depiction of atherosclerotic disease and subsequent luminal stenosis in the arteries that supplies the brain with blood, and 2) the assessment of atherosclerotic plaque features that have been related to plaque vulnerability.

  5. 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

    Directory of Open Access Journals (Sweden)

    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.

  6. Biology of atherosclerotic plaque formation: possible role of growth factors in lesion development and the potential impact of soy.

    Science.gov (United States)

    Raines, E W; Ross, R

    1995-03-01

    The advanced lesions of atherosclerosis occlude the affected artery by increasing the thickness of the intima. The focal thickening of the intima is due to a large increase in smooth muscle cells, formation of new connective tissue matrix by these smooth muscle cells and, in hyperlipidemic individuals, the accumulation of intracellular and extracellular lipid. Additionally, monocytes and T lymphocytes infiltrate the artery wall. Various forms of "injury" may lead to cellular infiltration and proliferation. Localized cellular infiltration of monocytes and T cells may be due to changes in adhesive properties of the endothelial surface, involving the expression of specific adhesion molecules. The directed cell migration and proliferation may represent the cells' response to polypeptide growth factors, acting singly or in concert. These peptide growth factors also modulate matrix synthesis and degradation, angiogenesis, cell-cell adhesion and cellular metabolism, including lipid uptake. In atherosclerosis, growth factors may be delivered by infiltrating cells or by activation of cells within the artery wall. Normally, growth factors and their cell-surface receptors are expressed at low or undetectable levels. Their up-regulation in early and developing atherosclerotic lesions suggests a pathogenic role for these molecules. Increased levels of isoflavonoids, in particular genistein, which are associated with consumption of soy-based diets, inhibit cell adhesion, alter growth factor activity and inhibit cell proliferation involved in lesion formation.

  7. Inhibition of lipoprotein-associated phospholipase A2 ameliorates inflammation and decreases atherosclerotic plaque formation in ApoE-deficient mice.

    Directory of Open Access Journals (Sweden)

    Wen-yi Wang

    Full Text Available BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2 is thought to play modulatory roles in the development of atherosclerosis. Here we evaluated the effects of a specific lp-PLA2 inhibitor on atherosclerosis in ApoE-deficient mice and its associated mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: ApoE-deficient mice fed an atherogenic high-fat diet for 17 weeks were divided into two groups. One group was administered the specific lp-PLA2 inhibitor, darapladib (50 mg/kg/day; p.o. daily for 6 weeks, while the control group was administered saline. We observed no differences in body weight and serum lipids levels between the two groups at the end of the dietary period. Notably, serum lp-PLA2 activity as well as hs-CRP (C-reactive protein and IL-6 (Interleukin-6 levels were significantly reduced in the darapladib group, compared with the vehicle group, while the serum PAF (platelet-activating factor levels were similar between the two groups. Furthermore, the plaque area through the arch to the abdominal aorta was reduced in the darapladib group. Another finding of interest was that the macrophage content was decreased while collagen content was increased in atherosclerotic lesions at the aortic sinus in the darapladib group, compared with the vehicle group. Finally, quantitative RT-PCR performed to determine the expression patterns of specific inflammatory genes at atherosclerotic aortas revealed lower expression of MCP-1, VCAM-1 and TNF-α in the darapladib group. CONCLUSIONS/SIGNIFICANCE: Inhibition of lp-PLA2 by darapladib leads to attenuation of in vivo inflammation and decreased plaque formation in ApoE-deficient mice, supporting an anti-atherogenic role during the progression of atherosclerosis.

  8. Modeling of Experimental Atherosclerotic Plaque Delamination.

    Science.gov (United States)

    Leng, Xiaochang; Chen, Xin; Deng, Xiaomin; Sutton, Michael A; Lessner, Susan M

    2015-12-01

    A cohesive zone model (CZM) approach is applied to simulate atherosclerotic plaque delamination experiments in mouse abdominal aorta specimens. A three-dimensional finite element model is developed for the experiments. The aortic wall is treated as a fiber-reinforced, highly deformable, incompressible material, and the Holzapfel-Gasser-Ogden (HGO) model is adopted for the aortic bulk material behavior. Cohesive elements are placed along the plaque-media interface along which delamination occurs. The 3D specimen geometry is created based on images from the experiments and certain simplifying approximations. A set of HGO and CZM parameter values is determined based on values suggested in the literature and through matching simulation predictions of the load vs. load-point displacement curve with experimental measurements for one loading-delamination-unloading cycle. Using this set of parameter values, simulation predictions for four other loading-delamination-unloading cycles are obtained, which show good agreement with experimental measurements. The findings of the current study demonstrate the applicability of the CZM approach in arterial tissue failure simulations.

  9. Atherosclerotic plaque rupture: local or systemic process?

    NARCIS (Netherlands)

    Lutgens, Esther; van Suylen, Robert-Jan; Faber, Birgit C.; Gijbels, Marion J.; Eurlings, Petra M.; Bijnens, Ann-Pascale; Cleutjens, Kitty B.; Heeneman, Sylvia; Daemen, Mat J. A. P.

    2003-01-01

    It is generally established that the unstable plaque is the major cause of acute clinical sequelae of atherosclerosis. Unfortunately, terms indicating lesions prone to plaque instability, such as "vulnerable plaque," and the different phenotypes of unstable plaques, such as plaque rupture, plaque

  10. In silico analyses of metagenomes from human atherosclerotic plaque samples

    DEFF Research Database (Denmark)

    Mitra, Suparna; Drautz-Moses, Daniela I; Alhede, Morten

    2015-01-01

    a challenge. RESULTS: To investigate microbiome diversity within human atherosclerotic tissue samples, we employed high-throughput metagenomic analysis on: (1) atherosclerotic plaques obtained from a group of patients who underwent endarterectomy due to recent transient cerebral ischemia or stroke. (2......) Presumed stabile atherosclerotic plaques obtained from autopsy from a control group of patients who all died from causes not related to cardiovascular disease. Our data provides evidence that suggest a wide range of microbial agents in atherosclerotic plaques, and an intriguing new observation that shows...... these microbiota displayed differences between symptomatic and asymptomatic plaques as judged from the taxonomic profiles in these two groups of patients. Additionally, functional annotations reveal significant differences in basic metabolic and disease pathway signatures between these groups. CONCLUSIONS: We...

  11. Correlation between aortic/carotid atherosclerotic plaques and cerebral infarction.

    Science.gov (United States)

    Wang, Baojun; Sun, Shaoli; Liu, Guorong; Li, Yuechun; Pang, Jiangxia; Zhang, Jingfen; Yang, Lijuan; Li, Ruiming; Zhang, Hui; Jiang, Changchun; Li, Xiue

    2013-08-01

    The aim of this study was to investigate the correlation between aortic/carotid atherosclerotic plaques and cerebral infarction. We examined 116 cases of cerebral infarction using transcranial Doppler ultrasound in order to exclude cerebrovascular stenosis. Transesophageal echocardiography and color Doppler ultrasound were used to detect aortic atherosclerotic plaques (AAPs) and carotid atherosclerotic plaques (CAPs). AAPs were detected in a total of 70 of the 116 cases (60.3%), including 56 with moderate/severe atherosclerotic changes (48.3%). The difference in the incidence of various types of infarction between APP severity levels was significant (PCAPs (55.2%), including 46 with unstable plaque (39.7%). The difference in the incidence of various types of infarction between CAP stability levels was significant (PCAP are significant causes of embolic infarction without stenosis in the internal carotid arteries.

  12. Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques

    Science.gov (United States)

    Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

    2016-03-01

    Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification areas. We also show that calcification morphology and the plaque’s collagen content--two determinants of atherosclerotic plaque stability--are interlinked.

  13. Review: Mechanical Characterization of Carotid Arteries and Atherosclerotic Plaques.

    Science.gov (United States)

    de Korte, Chris L; Fekkes, Stein; Nederveen, Aart J; Manniesing, Rashindra; Hansen, Hendrik Rik H G

    2016-10-01

    Cardiovascular disease (CVD) is a leading cause of death and is in the majority of cases due to the formation of atherosclerotic plaques in arteries. Initially, thickening of the inner layer of the arterial wall occurs. Continuation of this process leads to plaque formation. The risk of a plaque to rupture and thus to induce an ischemic event is directly related to its composition. Consequently, characterization of the plaque composition and its proneness to rupture are of crucial importance for risk assessment and treatment strategies. The carotid is an excellent artery to be imaged with ultrasound because of its superficial position. In this review, ultrasound-based methods for characterizing the mechanical properties of the carotid wall and atherosclerotic plaque are discussed. Using conventional echography, the intima media thickness (IMT) can be quantified. There is a wealth of studies describing the relation between IMT and the risk for myocardial infarction and stroke. Also the carotid distensibility can be quantified with ultrasound, providing a surrogate marker for the cross-sectional mechanical properties. Although all these parameters are associated with CVD, they do not easily translate to individual patient risk. Another technique is pulse wave velocity (PWV) assessment, which measures the propagation of the pressure pulse over the arterial bed. PWV has proven to be a marker for global arterial stiffness. Recently, an ultrasound-based method to estimate the local PWV has been introduced, but the clinical effectiveness still needs to be established. Other techniques focus on characterization of plaques. With ultrasound elastography, the strain in the plaque due to the pulsatile pressure can be quantified. This technique was initially developed using intravascular catheters to image coronaries, but recently noninvasive methods were successfully developed. A high correlation between the measured strain and the risk for rupture was established. Acoustic

  14. Haemodynamical stress in mouse aortic arch with atherosclerotic plaques: Preliminary study of plaque progression

    OpenAIRE

    Assemat, P.; Siu, K.K.; Armitage, J.A.; Hokke, S.N.; Dart, A; Chin-Dusting, J; Hourigan, K.

    2014-01-01

    Atherosclerotic plaques develop at particular sites in the arterial tree, and this regional localisation depends largely on haemodynamic parameters (such as wall shear stress; WSS) as described in the literature. Plaque rupture can result in heart attack or stroke and hence understanding the development and vulnerability of atherosclerotic plaques is critically important. The purpose of this study is to characterise the haemodynamics of blood flow in the mouse aortic arch using numerical mode...

  15. 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.

  16. Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.

    Directory of Open Access Journals (Sweden)

    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.

  17. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque.

    Science.gov (United States)

    Goel, Sunny; Miller, Avraham; Agarwal, Chirag; Zakin, Elina; Acholonu, Michael; Gidwani, Umesh; Sharma, Abhishek; Kulbak, Guy; Shani, Jacob; Chen, On

    2015-01-01

    Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level.

  18. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    Directory of Open Access Journals (Sweden)

    Sunny Goel

    2015-01-01

    Full Text Available Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level.

  19. Complement factor C5a induces atherosclerotic plaque disruptions

    Science.gov (United States)

    Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul HA; Bot, Ilze

    2014-01-01

    Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE−/− mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. PMID:25124749

  20. Decreased cathepsin K levels in human atherosclerotic plaques are associated with plaque instability.

    Science.gov (United States)

    Zhao, Huiying; Qin, Xiujiao; Wang, Shuai; Sun, Xiwei; Dong, Bin

    2017-10-01

    Investigating the determinants and dynamics of atherosclerotic plaque instability is a key area of current cardiovascular research. Extracellular matrix degradation from excessive proteolysis induced by enzymes such as cathepsin K (Cat K) is implicated in the pathogenesis of unstable plaques. The current study assessed the expression of Cat K in human unstable atherosclerotic plaques. Specimens of popliteal arteries with atherosclerotic plaques were classified as stable (K and cystatin C (Cys C) were assessed by immunohistochemical examination and levels of Cat K mRNA were detected by semi-quantitative reverse transcriptase polymerase chain reaction. Morphological changes including a larger lipid core, endothelial proliferation with foam cells and destruction of internal elastic lamina were observed in unstable atherosclerotic plaques. In unstable plaques, the expression of Cat K protein and mRNA was upregulated, whereas Cys C protein expression was downregulated. The interplay between Cat K and Cys C may underlie the progression of plaques from stable to unstable and the current study indicated that Cat K and Cys C are potential targets for preventing and treating vulnerable atherosclerotic plaque ruptures.

  1. Vulnerable atherosclerotic plaque detection by resonance Raman spectroscopy

    Science.gov (United States)

    Liu, Cheng-hui; Boydston-White, Susie; Weisberg, Arel; Wang, Wubao; Sordillo, Laura A.; Perotte, Adler; Tomaselli, Vincent P.; Sordillo, Peter P.; Pei, Zhe; Shi, Lingyan; Alfano, Robert R.

    2016-12-01

    A clear correlation has been observed between the resonance Raman (RR) spectra of plaques in the aortic tunica intimal wall of a human corpse and three states of plaque evolution: fibrolipid plaques, calcified and ossified plaques, and vulnerable atherosclerotic plaques (VPs). These three states of atherosclerotic plaque lesions demonstrated unique RR molecular fingerprints from key molecules, rendering their spectra unique with respect to one another. The vibrational modes of lipids, cholesterol, carotenoids, tryptophan and heme proteins, the amide I, II, III bands, and methyl/methylene groups from the intrinsic atherosclerotic VPs in tissues were studied. The salient outcome of the investigation was demonstrating the correlation between RR measurements of VPs and the thickness measurements of fibrous caps on VPs using standard histopathology methods, an important metric in evaluating the stability of a VP. The RR results show that VPs undergo a structural change when their caps thin to 66 μm, very close to the 65-μm empirical medical definition of a thin cap fibroatheroma plaque, the most unstable type of VP.

  2. Characterization of HSP27 phosphorylation sites in human atherosclerotic plaque secretome

    DEFF Research Database (Denmark)

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

    2007-01-01

    Atherosclerosis is one of the main causes of death in developed countries. Atheroma plaque formation is promoted by the interaction between the cells conforming the arterial wall, smooth muscle cells, and endothelial cells, together with lipoproteins and inflammatory cells (mainly macrophages and T......-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......, 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...

  3. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    OpenAIRE

    Goel, Sunny; Miller, Avraham; Agarwal, Chirag; Zakin, Elina; Acholonu, Michael; Gidwani, Umesh; Sharma, Abhishek; Kulbak, Guy; Shani, Jacob; Chen, On

    2015-01-01

    Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstabl...

  4. 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.

  5. Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression

    NARCIS (Netherlands)

    Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

    AIMS: Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte

  6. Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque

    Science.gov (United States)

    Hamblin, Michael R.; Tawakol, Ahmed; Castano, Ana P.; Gad, Faten; Zahra, Touqir; Ahmadi, Atosa; Stern, Jeremy; Ortel, Bernhard; Chirico, Stephanie; Shirazi, Azadeh; Syed, Sakeena; Muller, James E.

    2003-06-01

    Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular

  7. Atherosclerotic plaque detection by confocal Brillouin and Raman microscopies

    Science.gov (United States)

    Meng, Zhaokai; Basagaoglu, Berkay; Yakovlev, Vladislav V.

    2015-02-01

    Atherosclerosis, the development of intraluminal plaque, is a fundamental pathology of cardiovascular system and remains the leading cause of morbidity and mortality worldwide. Biomechanical in nature, plaque rupture occurs when the mechanical properties of the plaque, related to the morphology and viscoelastic properties, are compromised, resulting in intraluminal thrombosis and reduction of coronary blood flow. In this report, we describe the first simultaneous application of confocal Brillouin and Raman microscopies to ex-vivo aortic wall samples. Such a non-invasive, high specific approach allows revealing a direct relationship between the biochemical and mechanical properties of atherosclerotic tissue.

  8. Uniaxial tensile testing approaches for characterisation of atherosclerotic plaques.

    Science.gov (United States)

    Walsh, M T; Cunnane, E M; Mulvihill, J J; Akyildiz, A C; Gijsen, F J H; Holzapfel, G A

    2014-03-03

    The pathological changes associated with the development of atherosclerotic plaques within arterial vessels result in significant alterations to the mechanical properties of the diseased arterial wall. There are several methods available to characterise the mechanical behaviour of atherosclerotic plaque tissue, and it is the aim of this paper to review the use of uniaxial mechanical testing. In the case of atherosclerotic plaques, there are nine studies that employ uniaxial testing to characterise mechanical behaviour. A primary concern regarding this limited cohort of published studies is the wide range of testing techniques that are employed. These differing techniques have resulted in a large variance in the reported data making comparison of the mechanical behaviour of plaques from different vasculatures, and even the same vasculature, difficult and sometimes impossible. In order to address this issue, this paper proposes a more standardised protocol for uniaxial testing of diseased arterial tissue that allows for better comparisons and firmer conclusions to be drawn between studies. To develop such a protocol, this paper reviews the acquisition and storage of the tissue, the testing approaches, the post-processing techniques and the stress-strain measures employed by each of the nine studies. Future trends are also outlined to establish the role that uniaxial testing can play in the future of arterial plaque mechanical characterisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Complement factor C5a induces atherosclerotic plaque disruptions.

    Science.gov (United States)

    Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul H A; Bot, Ilze

    2014-10-01

    Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE(-/-) mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. A new finite element method for inverse problems in structural analysis: application to atherosclerotic plaque elasticity reconstruction

    OpenAIRE

    Bouvier, Adeline,; Deleaval, Flavien; Doyley, Marvin,; Tacheau, Antoine,; Finet, Gérard; Lefloch, Simon; Cloutier, Guy; Pettigrew, Roderic; Ohayon, Jacques

    2014-01-01

    International audience; Atherosclerotic plaque rupture remains the leading cause of acute coronary syndrome (ACS), myocardial infarction and stroke (Lloyd-Jones et al. 2010). Atherosclerotic lesions develop inside the arterial wall. Vulnerable plaque (VP), which is characterised by a relatively large extracellular necrotic core and a thin fibrous cap infiltrated by macrophages, is prone to rupture (Virmani et al. 2000). The rupture of the thin-cap fibroatheroma may lead to the formation of a ...

  11. Research Progress on the Risk Factors and Outcomes of Human Carotid Atherosclerotic Plaques.

    Science.gov (United States)

    Xiong, Xiang-Dong; Xiong, Wei-Dong; Xiong, Shang-Shen; Chen, Gui-Hai

    2017-03-20

    Atherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention. We searched the PubMed database for recently published research articles up to June 2016, with the key words of "risk factors", "outcomes", "blood components", "molecular mechanisms", "cellular mechanisms", and "human carotid atherosclerotic plaques". The articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected. This review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque. Carotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis.

  12. 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

  13. Compressive mechanical properties of atherosclerotic plaques - Indentation test to characterise the local anisotropic behaviour

    NARCIS (Netherlands)

    C.-K. Chai (Chen-Ket); L. Speelman (Lambert); C.W.J. Oomens (Cees); F.P.T. Baaijens (Frank)

    2014-01-01

    textabstractAccurate material models and associated parameters of atherosclerotic plaques are crucial for reliable biomechanical plaque prediction models. These biomechanical models have the potential to increase our understanding of plaque progression and failure, possibly improving risk assessment

  14. Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

    Science.gov (United States)

    2015-01-01

    Background Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue. Methods Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue. Results Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen. Conclusions Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large

  15. Detection and characterization of atherosclerotic plaques by Raman probe spectroscopy and optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Matthäus, Christian; Dochow, Sebastian; Egodage, Kokila D.; Schie, Iwan; Romeike, Bernd F.; Brehm, Bernhard R.; Popp, Jürgen

    2017-02-01

    Visualization and characterization of inner arterial plaque depositions is of vital diagnostic interest. Established intravascular imaging techniques provide valuable morphological information, but cannot deliver information about the chemical composition of individual plaques. Probe based Raman spectroscopy offers the possibility for a biochemical characterization of atherosclerotic plaque formations during an intravascular intervention. From post mortem studies it is well known that the severity of a plaque and its stability are strongly correlated with its biochemical composition. Especially the identification of vulnerable plaques remains one of the most important and challenging aspects in cardiology. Thus, specific information about the composition of a plaque would greatly improve the risk assessment and management. Furthermore, knowledge about the composition can offer new therapeutic and medication strategies. Plaque calcifications as well as major lipid components such as cholesterol, cholesterol esters and triglycerides can be spectroscopically easily differentiated. Intravascular optical coherence tomography (OCT) is currently a prominent catheter based imaging technique for the localization and visualization of atherosclerotic plaque depositions. The high resolution of OCT with 10 to 15 µm allows for very detailed characterization of morphological features such as different plaque formations, thin fibrous caps and accurate measurements of lesion lengths. In combination with OCT imaging the obtained spectral information can provide substantial information supporting on on-site diagnosis of various plaque types and therefor an improved risk assessment. The potential and feasibility of combining OCT with Raman spectroscopy is demonstrated on excised plaque samples, as well as under in vivo conditions. Acknowledgements: Financial support from the Carl Zeiss Foundation is greatly acknowledged.

  16. 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.

  17. Gene expression and 18FDG uptake in atherosclerotic carotid plaques

    DEFF Research Database (Denmark)

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

    2010-01-01

    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......) 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...... destabilization. Accordingly, FDG-PET could prove to be an important predictor of cerebrovascular events in patients with carotid plaques....

  18. Evaluation of the incidence of periodontitis-associated bacteria in the atherosclerotic plaque of coronary blood vessels.

    Science.gov (United States)

    Zaremba, Maciej; Górska, Renata; Suwalski, Piotr; Kowalski, Jan

    2007-02-01

    Unstable atherosclerotic plaque is a dangerous clinical condition, possibly leading to acute coronary deficiency resulting in cardiac infarction. Questions about the role of inflammatory factors in the formation of pathological lesions in the endothelium of coronary vessels have often been raised. This condition may be caused by bacteria that are able to initiate clot formation in a blood vessel, destabilizing an atherosclerotic plaque that is already present. The sources of these pathogens are chronic inflammatory processes occurring in the host, including periodontal disease, which is one of the most frequent conditions. The aim of this study was to evaluate the incidence of selected anaerobic bacteria in subgingival and atherosclerotic plaque in patients treated surgically because of coronary vessel obliteration. The study was performed on 20 individuals with chronic periodontitis. Subgingival plaque was collected from periodontal pockets >5 mm. DNA testing was used to identify eight pathogens responsible for periodontal tissue destruction. Material from atherosclerotic plaques was collected from the same patients during bypass surgery, and DNA testing by the same method was performed. In 13 of 20 patients, the pathogens most frequently found in severe chronic periodontitis were also found in coronary vessels. In 10 cases, those species of bacteria were also present in atherosclerotic plaque. The most frequently identified bacteria were Porphyromonas gingivalis and Treponema denticola. In patients with the severe form of chronic periodontitis, it seems that clinical attachment loss is not associated with bacterial permeability into coronary vessels. What is important is the presence of an active inflammatory process expressed by a significantly higher bleeding index in those patients in whom the examined bacterial species were found in atherosclerotic plaque.

  19. Identification of Atherosclerotic Plaques in Carotid Artery by Fluorescence Spectroscopy

    Science.gov (United States)

    Rocha, Rick; Villaverde, Antonio Balbin; Silveira, Landulfo; Costa, Maricília Silva; Alves, Leandro Procópio; Pasqualucci, Carlos Augusto; Brugnera, Aldo

    2008-04-01

    The aim of this work was to identify the presence of atherosclerotic plaques in carotid artery using the Fluorescence Spectroscopy. The most important pathogeny in the cardiovascular disorders is the atherosclerosis, which may affect even younger individuals. With approximately 1.2 million heart attacks and 750,000 strokes afflicting an aging American population each year, cardiovascular disease remains the number one cause of death. Carotid artery samples were obtained from the Autopsy Service at the University of São Paulo (São Paulo, SP, Brazil) taken from cadavers. After a histopathological analysis the 60 carotid artery samples were divided into two groups: normal (26) and atherosclerotic plaques (34). Samples were irradiated with the wavelength of 488 nm from an Argon laser. A 600 μm core optical fiber, coupled to the Argon laser, was used for excitation of the sample, whereas another 600 optical fiber, coupled to the spectrograph entrance slit, was used for collecting the fluorescence from the sample. Measurements were taken at different points on each sample and then averaged. Fluorescence spectra showed a single broad line centered at 549 nm. The fluorescence intensity for each sample was calculated by subtracting the intensity at the peak (550 nm) and at the bottom (510 nm) and then data were statistically analyzed, looking for differences between both groups of samples. ANOVA statistical test showed a significant difference (p<0,05) between both types of tissues, with regard to the fluorescence peak intensities. Our results indicate that this technique could be used to detect the presence of the atherosclerotic in carotid tissue.

  20. 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

  1. Associations of Osteocalcin, Osteoprotegerin, and Calcitonin with Inflammation Biomarkers in Atherosclerotic Plaques of Coronary Arteries.

    Science.gov (United States)

    Polonskaya, Ya V; Kashtanova, E V; Murashov, I S; Volkov, A M; Kurguzov, A V; Chernyavsky, A M; Ragino, Yu I

    2017-04-01

    We studied associations of osteocalcin, osteoprotegerin, and calcitonin with markers of inflammation in atherosclerotic plaques in coronary arteries and assessed the influence of these biomolecules on calcification of atherosclerotic plaques. The initial stage of calcification of atherosclerotic plaques is characterized by activation of inflammatory processes, which is seen from increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-α, and IL-1β). Progressive calcification of atherosclerotic plaques is accompanied by insignificant accumulation of calcitonin and osteoprotegerin. The exception is osteocalcin, its concentration significantly increased during calcification. The results suggest that severe vascular calcification can be regarded as non-specific marker of atherosclerosis. Instability of atherosclerotic plaques is associated with higher level of calcification.

  2. Murine atherosclerotic plaque imaging with the USPIO Ferumoxtran-10.

    Science.gov (United States)

    Klug, Gert; Kampf, Thomas; Ziener, Christan; Parczyk, Marco; Bauer, Elizabeth; Herold, Volker; Rommel, Eberhard; Jakob, Peter Michael; Bauer, Wolfgang Rudolf

    2009-01-01

    In this study we intended to image plaque inflammation in a murine model of atherosclerosis with MRI and Ferumoxtran-10 (Sinerem, Guerbet, France). 8 apoE-/- mice were injected 500 micromol Fe/kg or 1000 micromol Fe/kg Ferumoxtran-10. 2 apoE-/- mice were injected NaCl. After a post-contrast time of 24 to 336 hours the mice were scarificed and the aortas were imaged ex vivo. All measurements were performed on a 17.6 Tesla Bruker AVANCE 750WB MR scanner (Bruker, Germany). Spin-echo sequences and gradient-echo sequences with variable TE were performed and T2* maps were generated. Prussian-blue and hematoxilin-eosin histology were obtained afterwards and iron-uptake was quantified by counting iron positive areas. 2 apoE-/- mice were imaged in vivo before and 48 hours after 1000 micromol Fe/kg. Atheroma iron uptake was not elevated after 24 hours compared to controls. 48 hours after 1000 micromol Fe/kg but not 500 micromol Fe/kg histology revealed a 1.3- fold increase in plaque iron content compared to NaCl injected mice. Normalized T2*-times decreased from 0.86+/-0.02 in controls to 0.66+/-0.15 after a dose of 500 micromol Fe/ml and 0.59+/-0.14 in mice injected with 1000 micromol Fe/Kg (p=0.038). These results translated into a mean of 122% increase in CNR, as measured by in vivo MRI. We have demonstrated that Ferumoxtran-10 is taken up by atherosclerotic plaques in untreated apoE-/- mice and this alters plaque signal properties.

  3. Lymphatic vessels: an emerging actor in atherosclerotic plaque development.

    Science.gov (United States)

    Kutkut, Issa; Meens, Merlijn J; McKee, Thomas A; Bochaton-Piallat, Marie-Luce; Kwak, Brenda R

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease of large- to medium-sized arteries and is the main underlying cause of death worldwide. The lymphatic vasculature is critical for processes that are intimately linked to atherogenesis such as the immune response and cholesterol metabolism. However, whether lymphatic vessels truly contribute to the pathogenesis of atherosclerosis is less clear despite increasing research efforts in this field. PubMed and Ovid MEDLINE databases were searched. In addition, key review articles were screened for relevant original publications. Current knowledge about lymphatic vessels in the arterial wall came from studies that examined the presence and location of such vessels in human atherosclerotic plaque specimens, as well as in a variety of arteries in animal models for atherosclerosis (e.g. rabbits, dogs, rats and mice). Generally, three experimental approaches have been used to investigate the functional role of plaque-associated lymphatic vessels; experimental lymphostasis was used to investigate lymphatic drainage of the arterial wall, and more recently, studies with genetic interventions and/or surgical transplantation have been performed. Lymphatic vessels seem to be mostly present in the adventitial layer of the arterial walls of animals and humans. They are involved in reverse cholesterol transport from atherosclerotic lesions, and arteries with a dense lymphatic network seem naturally protected against atherosclerosis. Lymphangiogenesis is a process that is an important part of the inflammatory loop in atherosclerosis. However, how augmenting or impeding the distribution of lymphatic vessels impacts disease progression remains to be investigated in future studies. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  4. Texture based segmentation method to detect atherosclerotic plaque from optical tomography images

    Science.gov (United States)

    Prakash, Ammu; Hewko, Mark; Sowa, Michael; Sherif, Sherif

    2013-06-01

    Optical coherence tomography (OCT) imaging has been widely employed in assessing cardiovascular disease. Atherosclerosis is one of the major cause cardio vascular diseases. However visual detection of atherosclerotic plaque from OCT images is often limited and further complicated by high frame rates. We developed a texture based segmentation method to automatically detect plaque and non plaque regions from OCT images. To verify our results we compared them to photographs of the vascular tissue with atherosclerotic plaque that we used to generate the OCT images. Our results show a close match with photographs of vascular tissue with atherosclerotic plaque. Our texture based segmentation method for plaque detection could be potentially used in clinical cardiovascular OCT imaging for plaque detection.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  6. Differential effects of daily-moderate versus weekend-binge alcohol consumption on atherosclerotic plaque development in mice.

    Science.gov (United States)

    Liu, Weimin; Redmond, Eileen M; Morrow, David; Cullen, John P

    2011-12-01

    We examined the effect of daily-moderate (2 drinks/day, 7 days/week) and weekend-binge (7 drinks/day, 2 days/week) patterns of alcohol consumption on plasma lipid levels and physiological parameters of atherosclerotic plaque development. ApoE k/o mouse were fed (1) 'daily-moderate' (blood alcohol content: 0.07%) or (2) 'weekend-binge' (blood alcohol content: 0.23%), or (3) an isocaloric cornstarch mix. Then, to induce atherosclerotic plaque formation, all groups underwent partial carotid artery ligation, started on an atherogenic diet and continued on the alcohol feeding regimen. After 2 weeks plasma lipid levels and atherosclerotic plaque formation were assessed. While there was an increase in HDL-C levels in both binge and moderate groups, LDL-C levels were significantly decreased in the daily-moderate drinking mice and significantly elevated in the weekend-binge drinking mice. In the daily-moderate alcohol group there was a decrease in atherosclerotic plaque volume, concomitant with an increase in lumen volume and decreased macrophage accumulation, when compared to no alcohol mice. In contrast, after 4 weeks of weekend-binge alcohol there was an increase in plaque volume, concomitant with a decrease in lumen volume and increased deposition of macrophages. These findings demonstrate for the first time a differential effect of daily-moderate vs. weekend-binge alcohol consumption on atherosclerotic plaque development and highlight the importance of patterns of alcohol consumption, as opposed to total amount consumed, in relation to the cardiovascular effects of alcohol. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. 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.

  8. Leukotriene B4 levels in human atherosclerotic plaques and abdominal aortic aneurysms.

    Directory of Open Access Journals (Sweden)

    Pleunie van den Borne

    Full Text Available BACKGROUND: Leukotriene B4 (LTB4 has been associated with the initiation and progression of atherosclerosis and abdominal aortic aneurysm (AAA formation. However, associations of LTB4 levels with tissue characteristics and adverse clinical outcome of advanced atherosclerosis and AAA are scarcely studied. We hypothesized that LTB4 levels are associated with a vulnerable plaque phenotype and adverse clinical outcome. Furthermore, that LTB4 levels are associated with inflammatory AAA and adverse clinical outcome. METHODS: Atherosclerotic plaques and AAA specimens were selected from two independent databases for LTB4 measurements. Plaques were isolated during carotid endarterectomy from asymptomatic (n = 58 or symptomatic (n = 317 patients, classified prior to surgery. LTB4 levels were measured without prior lipid extraction and levels were corrected for protein content. LTB4 levels were related to plaque phenotype, baseline patient characteristics and clinical outcome within three years following surgery. Seven non-diseased mammary artery specimens served as controls. AAA specimens were isolated during open repair, classified as elective (n = 189, symptomatic (n = 29 or ruptured (n = 23. LTB4 levels were measured similar to the plaque measurements and were related to tissue characteristics, baseline patient characteristics and clinical outcome. Twenty-six non-diseased aortic specimens served as controls. RESULTS: LTB4 levels corrected for protein content were not significantly associated with histological characteristics specific for vulnerable plaques or inflammatory AAA as well as clinical presentation. Moreover, it could not predict secondary manifestations independently investigated in both databases. However, LTB4 levels were significantly lower in controls compared to plaque (p = 0.025 or AAA (p = 0.017. CONCLUSIONS: LTB4 levels were not associated with a vulnerable plaque phenotype or inflammatory AAA or clinical

  9. Vascular neuropeptide Y contributes to atherosclerotic plaque progression and perivascular mast cell activation.

    Science.gov (United States)

    Lagraauw, H Maxime; Westra, Marijke M; Bot, Martine; Wezel, Anouk; van Santbrink, Peter J; Pasterkamp, Gerard; Biessen, Erik A L; Kuiper, Johan; Bot, Ilze

    2014-07-01

    Neuropeptide Y is an abundantly expressed neurotransmitter capable of modulating both immune and metabolic responses related to the development of atherosclerosis. NPY receptors are expressed by a number of vascular wall cell types, among which mast cells. However, the direct effects of NPY on atherosclerotic plaque development and progression remain to be investigated. In this study we thus aimed to determine whether NPY is expressed in atherosclerotic plaques and to establish its role in atherosclerotic plaque development. NPY expression was seen to be increased up to 2-fold in unstable human endarterectomy plaques, as compared to stable plaques, and to be significantly upregulated during lesion progression in apoE(-/-) mice. In apoE(-/-) mice focal overexpression of NPY in the carotid artery significantly increased atherosclerotic plaque size compared to controls, while plaque composition was unaffected. Interestingly, perivascular mast cell activation was significantly higher in the NPY-overexpressing mice, suggesting that NPY may impact plaque progression in part via mast cell activation. Furthermore, in vitro NPY-induced murine mast cell activation resulted in the release of pro-atherogenic mediators including IL-6 and tryptase. Our data show that NPY expression is increased during atherogenesis and in particular in unstable plaques. Furthermore, perivascular overexpression of NPY promoted plaque development and perivascular mast cell activation, suggestive of a role for NPY-induced mast cell activation in lesion progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Paramagnetic Manganese in the Atherosclerotic Plaque of Carotid Arteries

    Directory of Open Access Journals (Sweden)

    Yury Chelyshev

    2016-01-01

    Full Text Available The search for adequate markers of atherosclerotic plaque (AP instability in the context of assessment of the ischemic stroke risk in patients with atherosclerosis of the carotid arteries as well as for solid physical and chemical factors that are connected with the AP stability is extremely important. We investigate the inner lining of the carotid artery specimens from the male patients with atherosclerosis (27 patients, 42–64 years old obtained during carotid endarterectomy by using different analytical tools including ultrasound angiography, X-ray analysis, immunological, histochemical analyses, and high-field (3.4 T pulse electron paramagnetic resonance (EPR at 94 GHz. No correlation between the stable and unstable APs in the sense of the calcification is revealed. In all of the investigated samples, the EPR spectra of manganese, namely, Mn2+ ions, are registered. Spectral and relaxation characteristics of Mn2+ ions are close to those obtained for the synthetic (nano hydroxyapatite species but differ from each other for stable and unstable APs. This demonstrates that AP stability could be specified by the molecular organization of their hydroxyapatite components. The origin of the obtained differences and the possibility of using EPR of Mn2+ as an AP stability marker are discussed.

  11. Angiopoietin-2 blocking antibodies reduce early atherosclerotic plaque development in mice

    NARCIS (Netherlands)

    Theelen, Thomas L.; Lappalainen, Jari P.; Sluimer, Judith C.; Gurzeler, Erika; Cleutjens, Jack P.; Gijbels, Marion J.; Biessen, Erik A. L.; Daemen, Mat J. A. P.; Alitalo, Kari; Ylä-Herttuala, Seppo

    2015-01-01

    Angiopoietin-2 (Ang-2) blocking agents are currently undergoing clinical trials for use in cancer treatment. Ang-2 has also been associated with rupture-prone atherosclerotic plaques in humans, suggesting a role for Ang-2 in plaque stability. Despite the availability of Ang-2 blocking agents, their

  12. 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...... 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.......001). Conclusions: Based on preliminary data, a quadratic relationship appears to exist between aging and plaque inflammation. In contrast, a linear relationship was observed between aging and plaque molecular calcification. These data reject the existence of a linear relationship between plaque inflammation...

  13. Preventive and therapeutic moderate aerobic exercise programs convert atherosclerotic plaques into a more stable phenotype.

    Science.gov (United States)

    Cardinot, Themis M; Lima, Thais M; Moretti, Ana I S; Koike, Marcia K; Nunes, Valeria S; Cazita, Patricia M; Krieger, Marta H; Brum, Patricia C; Souza, Heraldo P

    2016-05-15

    The mechanisms by which exercise affects atherosclerotic plaque stability remain incompletely understood. We evaluated the effects of two training protocols on both atherosclerotic plaque structure and the signaling pathways involved in plaque rupture. Male low-density lipoprotein (LDL) receptor knockout mice were fed a high-fat, high-cholesterol diet (HFD). One group was subjected to moderate exercise using a treadmill for 14weeks (preventive protocol). The other group started an exercise regimen after 16weeks of the HFD (therapeutic group). Atherosclerotic plaques within the aorta were evaluated for lipid and collagen contents, as well as for inflammatory markers. Plasma cholesterol and cytokine levels were also determined. The mice receiving a HFD developed hypercholesterolemia and atherosclerotic plaques within the aorta. The aortas from the animals in the preventive protocol exhibited smaller lipid cores and higher collagen content. These animals also exhibited lower CD40 expression within the plaques. The aortas of the mice in the therapeutic group exhibited higher collagen content, but no differences in either lipid core size or plaque size were noted. No differences in blood pressure, plasma cholesterol, cytokine levels, plaque size or metalloproteinase 9 expression were observed in the trained animals compared with the sedentary animals. Moderate aerobic exercise modified atherosclerotic plaque characteristics and converted the plaques into a more stable phenotype, increasing the collagen content in response to both exercise programs. Furthermore, moderate aerobic exercise reduced the animals' fat content and decreased the activity of the CD40-CD40L signaling pathway in the preventive group. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 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...... polymerase chain reaction in the final multivariate model, indicating that 64Cu-DOTATATE PET is detecting alternatively activated macrophages. This association could potentially improve noninvasive identification and characterization of vulnerable plaques....

  15. The role of damage- and pathogen-associated molecular patterns in inflammation-mediated vulnerability of atherosclerotic plaques.

    Science.gov (United States)

    Rai, Vikrant; Agrawal, Devendra K

    2017-10-01

    Atherosclerosis is a chronic inflammatory disease resulting in the formation of the atherosclerotic plaque. Plaque formation starts with the inflammation in fatty streaks and progresses through atheroma, atheromatous plaque, and fibroatheroma leading to development of stable plaque. Hypercholesterolemia, dyslipidemia, and hyperglycemia are the risk factors for atherosclerosis. Inflammation, infection with viruses and bacteria, and dysregulation in the endothelial and vascular smooth muscle cells leads to advanced plaque formation. Death of the cells in the intima due to inflammation results in secretion of damage-associated molecular patterns (DAMPs) such as high mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), alarmins (S100A8, S100A9, S100A12, and oxidized low-density lipoproteins), and infection with pathogens leads to secretion of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides, lipoteichoic acids, and peptidoglycans. DAMPs and PAMPs further activate the inflammatory surface receptors such as TREM-1 and toll-like receptors and downstream signaling kinases and transcription factors leading to increased secretion of pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-1β, IL-6, and interferon-γ and matrix metalloproteinases (MMPs). These mediators and cytokines along with MMPs render the plaque vulnerable for rupture leading to ischemic events. In this review, we have discussed the role of DAMPs and PAMPs in association with inflammation-mediated plaque vulnerability.

  16. Molecular analysis of oral bacteria in dental biofilm and atherosclerotic plaques of patients with vascular disease.

    Science.gov (United States)

    Fernandes, Clarissa Pessoa; Oliveira, Francisco Artur Forte; Silva, Paulo Goberlânio de Barros; Alves, Ana Paula Negreiros Nunes; Mota, Mário Rogério Lima; Montenegro, Raquel Carvalho; Burbano, Rommel Mario Rodriguez; Seabra, Aline Damasceno; Lobo Filho, José Glauco; Lima, Danilo Lopes Ferreira; Soares Filho, Antônio Wilon Evelin; Sousa, Fabrício Bitu

    2014-07-01

    Oral bacteria have been detected in atherosclerotic plaques at a variable frequency; however, the connection between oral health and vascular and oral bacterial profiles of patients with vascular disease is not clearly established. The aim of this study was to evaluate the presence of oral bacterial DNA in the mouth and atherosclerotic plaques, in addition to assessing the patients' caries and periodontal disease history. Thirty samples of supragingival and subgingival plaque, saliva and atherosclerotic plaques of 13 patients with carotid stenosis or aortic aneurysm were evaluated, through real-time polymerase chain reaction, for the presence of Streptococcus mutans (SM), Prevotella intermedia (PI), Porphyromonas gingivalis (PG) and Treponema denticola (TD). All patients were submitted to oral examination using the DMFT (decayed, missing and filled teeth) and PSR (Periodontal Screening and Recording) indexes. Histopathological analysis of the atherosclerotic plaques was performed. Most of the patients were edentulous (76.9%). SM, PI, PG and TD were detected in 100.0%, 92.0%, 15.3% and 30.7% of the oral samples, respectively. SM was the most prevalent targeted bacteria in atherosclerotic plaques, detected in 100% of the samples, followed by PI (7.1%). The vascular samples were negative for PG and TD. There was a statistically significant difference (p<0.05) between the presence of PG and TD in the oral cavity and vascular samples. SM was found at a high frequency in oral and vascular samples, even in edentulous patients, and its presence in atherosclerotic plaques suggests the possible involvement of this bacterium in the disease progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Role of infrasound pressure waves in atherosclerotic plaque rupture: a theoretical approach.

    Science.gov (United States)

    Tsatsaris, Athanasios; Koukounaris, Efstathios; Motsakos, Theodoros; Perrea, Despina

    2007-01-01

    To investigate the role of infrasound aortic pressure waves (IPW) in atherosclerotic plaque rupture. Atherosclerotic plaques have been simulated partly, in two dimensions, as being short or long Conical Intersections (CIS), that is to say elliptic, parabolic or hyperbolic surfaces. Consequently, the course and reflection of the generated aortic pressure wave (infrasound domain-less than 20Hz) has been examined around the simulated plaques. The incidence of IPW on plaque surface results both in reflection and "refraction" of the wave. The IPW course within tissue, seems to be enhanced by high Cu-level presence at these areas according to recent evidence (US2003000388213). The "refracted", derived wave travels through plaque tissue and is eventually accumulated to the foci of the respective CIS-plaque geometry. The foci location within or underneath atheroma declares zones where infrasound energy is mostly absorbed. This process, among other mechanisms may contribute to plaque rupture through the development of local hemorrhage and inflammation in foci areas. In future, detection of foci areas and repair (i.e. via Laser Healing Microtechnique) may attenuate atherosclerotic plaque rupture behavior.

  18. 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.

  19. Effect of rosuvastatin on inflammatory factors and carotid atherosclerotic plaque in patients with acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    YAN Jun

    2013-10-01

    Full Text Available Carotid atherosclerosis is closely related with ischemic stroke occurrence, development and recurrence. This study aims to make an evaluation of the effects of rosuvastatin on inflammatory factors, serum lipid and carotid atherosclerotic plaque in patients with acute ischemic stroke. In this study, 98 patients with acute ischemic stroke and carotid atherosclerosis were given oral administration of rosuvastatin calcium (10 mg once every night, and the course of treatment was 6 months. After treatment, the changes of serum high-sensitivity C-reactive protein (hs-CRP, tumor necrosis factor-alpha (TNF-α and blood lipid were measured, as well as carotid atherosclerotic intima-media thickness (IMT and the calculation of carotid atherosclerotic plaque score. According to the examination results, after 6 months' treatment with rosuvastatin, serum hs-CRP, TNF-α, total cholesterol (TC, triglyceride (TG and low-density lipoprotein cholestrol (LDL-C decreased significantly (P < 0.01, for all, while high-density lipoprotein cholestrol (HDL-C increased significantly (P < 0.01; the total number of plaque reduced, while the number of stable plaque increased (P < 0.05; carotid artery IMT and carotid artery plaque score decreased significantly (P < 0.05. There were significant differences between before and after treatment. The results of this study show that rosuvastatin plays a role in anti-inflammation and alleviates the degree of carotid atherosclerotic plaque.

  20. Intravascular photoacoustic imaging of exogenously labeled atherosclerotic plaque through luminal blood

    Science.gov (United States)

    Yeager, Doug; Karpiouk, Andrei; Wang, Bo; Amirian, James; Sokolov, Konstantin; Smalling, Richard; Emelianov, Stanislav

    2012-10-01

    Combined intravascular ultrasound and intravascular photoacoustic (IVUS/IVPA) imaging has been previously established as a viable means for assessing atherosclerotic plaque morphological and compositional characteristics using both endogenous and exogenous contrast. In this study, IVUS/IVPA imaging of atherosclerotic rabbit aortas following systemic injection of gold nanorods (AUNRs) with peak absorbance within the tissue optical window is performed. Ex vivo imaging results reveal a high photoacoustic signal from localized AUNRs in regions with atherosclerotic plaques. Corresponding histological staining further confirms the preferential extravasation of AUNRs in atherosclerotic regions with compromised luminal endothelium and acute inflammation. The ability to detect AUNRs using combined IVUS and photoacoustic imaging in the presence of luminal saline and luminal blood is evaluated using both spectroscopic and single wavelength IVPA imaging techniques. Results demonstrate that AUNR detection within the arterial wall can be achieved using both methods, even in the case of imaging through luminal blood.

  1. Delayed 18F-fluorodeoxyglucose PET/CT imaging improves quantitation of atherosclerotic plaque inflammation

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Thomassen, Anders; Takx, Richard A P

    2014-01-01

    BACKGROUND: This study aimed to determine if delayed (18)F-fluorodeoxyglucose ((18)FDG) PET/CT imaging improves quantitation of atherosclerotic plaque inflammation. Blood-pool activity can disturb the arterial (18)FDG signal. With time, blood-pool activity declines. Therefore, delayed imaging can...... at 180 minutes significant positive relations were observed between SCORE % and carotid (τ = 0.25, P = .045) and aortic (τ = 0.33, P = .008) cSUVMAX. CONCLUSIONS: Delayed (18)FDG PET/CT imaging at 180 minutes improves quantitation of atherosclerotic plaque inflammation over imaging at 90 minutes....... Therefore, the optimal acquisition time-point to assess atherosclerotic plaque inflammation lies beyond the advocated time-point of 90 minutes after (18)FDG administration....

  2. Assessment of atherosclerotic plaque inflammation can be improved by delayed time point FDG PET CT imaging

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

    2013-01-01

    Objectives: Blood pool FDG activity can cloud the atherosclerotic plaque FDG signal. Over time, blood pool FDG activity declines. Therefore, delayed time point FDG PET CT imaging can potentially enhance the assessment of atherosclerotic plaque inflammation. Methods: Twelve healthy volunteers...... without traditional cardiovascular risk factors and three subjects with angina pectoris were prospectively assessed by dual time point 18-FDG PET CT imaging at 90 and 180 minutes after tracer injection. The ratio between aortic SUVmax and the blood pool SUVmean (TBR) was calculated to show the change......,35; df = 12; P = 0.037). Conclusions: Based on these preliminary data, we can make three conclusions: 1) aging and male gender are significantly correlated to atherosclerotic plaque FDG avidity, 2) over time, a significant increase is observed in TBR, and 3) the increase in cSUV over time results...

  3. 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......-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...... with aortic calcifications compared to those without. CONCLUSIONS: Human macrophage foam cells degrade the atherosclerotic plaques though cathepsin K mediated processes, resulting in increase in levels of CTX-I. Serum CTX-I was not elevated in women with aortic calcification, likely due to the contribution...

  4. Insulin decreases atherosclerotic plaque burden and increases plaque stability via nitric oxide synthase in apolipoprotein E-null mice.

    Science.gov (United States)

    Mori, Yusaku; Chiang, Simon; Bendeck, Michelle P; Giacca, Adria

    2016-08-01

    It has been argued whether insulin accelerates or prevents atherosclerosis. Although results from in vitro studies have been conflicting, recent in vivo mice studies demonstrated antiatherogenic effects of insulin. Insulin is a known activator of endothelial nitric oxide synthase (NOS), leading to increased production of NO, which has potent antiatherogenic effects. We aimed to examine the role of NOS in the protective effects of insulin against atherosclerosis. Male apolipoprotein E-null mice (8 wk old) fed a high-cholesterol diet (1.25% cholesterol) were assigned to the following 12-wk treatments: control, insulin (0.05 U/day via subcutaneous pellet), N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME, via drinking water at 100 mg/l), and insulin plus l-NAME. Insulin reduced atherosclerotic plaque burden in the descending aorta by 42% compared with control (plaque area/aorta lumen area: control, 16.5 ± 1.9%; insulin, 9.6 ± 1.3%, P < 0.05). Although insulin did not decrease plaque burden in the aortic sinus, macrophage accumulation in the plaque was decreased by insulin. Furthermore, insulin increased smooth muscle actin and collagen content and decreased plaque necrosis, consistent with increased plaque stability. In addition, insulin treatment increased plasma NO levels, decreased inducible NOS staining, and tended to increase phosphorylated vasodilator-stimulated phosphoprotein staining in the plaques of the aortic sinus. All these effects of insulin were abolished by coadministration of l-NAME, whereas l-NAME alone showed no effect. Insulin also tended to increase phosphorylated endothelial NOS and total neuronal NOS staining, effects not modified by l-NAME. In conclusion, we demonstrate that insulin treatment decreases atherosclerotic plaque burden and increases plaque stability through NOS-dependent mechanisms. Copyright © 2016 the American Physiological Society.

  5. The content of copper and zinc in human ulcered atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Radak Đorđe

    2004-01-01

    Full Text Available INTRODUCTION Copper and zinc have significant antiatherogenic effect influencing activity of antioxidant enzyms (giutathion-peroxidase i superoxid-dismutase, mechanism of apoptosis and other mechanisms. Few studies showed increased copper and zinc concentration in atherosclerotic plaque in comparison to normal vascular tissue. AIM The aim of the study was to compare copper and zinc concentrations in carotid artery tissue without significant atherosclerotic changes and human ulcered atherosclerotic plaque. MATERIAL AND METHODS Study was conducted on 66 patients. Carotid endarterectomy due to the significant carotid atherosclerotic changes with cerebrovascular disorders was performed in 54 patients (81.8%. Control group consisted of 12 patients (18.2% without carotid atherosclerotic changes operated due to the symptomatic kinking and coiling of carotid artery. Operated group consisted of 38 man (62.96% and 16 woman (37.04%. Control group had the same number of patients: six men (50% and six women (50%. Preoperatively, all patients were examined by vascular surgeon, neurologist and cardiologist. Duplex sonografy of carotid and vertebral arteries was performed by Aloca DSD 630 ultrasound with mechanical and linear transducer 7.7 MHz. Indication for surgical treatment was obtained according to non-invasive diagnostic protocol and neurological symptoms. Copper and zinc concentration in human ulcered atherosclerotic plaque and carotid artery segment were estimated by spectophotometry (Varian AA-5. RESULTS Average age of our patients was 59.8±8.1 years. For males average age was 76.1 ±9.8 years. And for females 42.4±5.8 years. In group with carotid endarterectomy female patients were significantly younger than male patients (p<0.01. In group with carotid endarterectomy clinically determined neurological disorders were found in 47 patients (87.03%-35 male (74.47% and 12 female patients (25.53%. Regarding risk factors for cardiovascular diseases, no

  6. {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.)

  7. Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase

    DEFF Research Database (Denmark)

    Morgan, P E; Laura, R P; Maki, R A

    2015-01-01

    the curve (AUC). Mean serum SCN(-) concentrations were elevated in the supplemented mice (200-320 μM) relative to controls (plaque areas at sacrifice were 26% lower in the SCN(-)-supplemented mice compared with controls (P = 0.0417), but plaque morphology...... was not appreciably altered. Serum MPO levels steadily increased in mice on the high-fat diet, however, comparison of SCN(-)-supplemented versus control mice showed no significant changes in MPO protein, cholesterol, or triglyceride levels; thiol levels were decreased in supplemented mice at one time-point. Plaque...

  8. Positron emission tomography of the vulnerable atherosclerotic plaque in man – a contemporary review

    DEFF Research Database (Denmark)

    Pedersen, Sune F; Hag, Anne Mette F; Klausen, Thomas L

    2014-01-01

    to treat symptomatic patients with high-grade carotid artery stenosis due to atherosclerosis - a procedure known as carotid endarterectomy (CEA). By removing the atherosclerotic plaque from the affected carotid artery of these patients, CEA is beneficial by preventing subsequent ipsilateral ischemic stroke...

  9. 3D reconstruction of carotid atherosclerotic plaque: comparison between spatial compound ultrasound models and anatomical models

    DEFF Research Database (Denmark)

    Lind, Bo L.; Fagertun, Jens; Wilhjelm, Jens E.

    2007-01-01

    This study deals with the creation of 3D models that can work as a tool for discriminating between tissue and background in the development of tissue classification methods. Ten formalin-fixed atherosclerotic carotid plaques removed by endarterectomy were scanned with 3D multi-angle spatial...

  10. β-Sarcoglycan Deficiency Reduces Atherosclerotic Plaque Development in ApoE-Null Mice.

    Science.gov (United States)

    Murugesan, Vignesh; Degerman, Eva; Holmen-Pålbrink, Ann-Kristin; Duner, Pontus; Knutsson, Anki; Hultgårdh-Nilsson, Anna; Rauch, Uwe

    2017-01-01

    Smooth muscle cells are important for atherosclerotic plaque stability. Their proper ability to communicate with the extracellular matrix is crucial for maintaining the correct tissue integrity. In this study, we have investigated the role of β-sarcoglycan within the matrix-binding dystrophin-glycoprotein complex in the development of atherosclerosis. Atherosclerotic plaque development was significantly reduced in ApoE-deficient mice lacking β-sarcoglycan, and their plaques contained an increase in differentiated smooth muscle cells. ApoE-deficient mice lacking β-sarcoglycan showed a reduction in ovarian adipose tissue and adipocyte size, while the total weight of the animals was not significantly different. Western blot analysis of adipose tissues showed a decreased activation of protein kinase B, while that of AMP-activated kinase was increased in mice lacking β-sarcoglycan. Analysis of plasma in β-sarcoglycan-deficient mice revealed reduced levels of leptin, adiponectin, insulin, cholesterol, and triglycerides but increased levels of IL-6, IL-17, and TNF-α. Our results indicate that the dystrophin-glycoprotein complex and β-sarcoglycan can affect the atherosclerotic process. Furthermore, the results show the effects of β-sarcoglycan deficiency on adipose tissue and lipid metabolism, which may also have contributed to the atherosclerotic plaque reduction. © 2017 S. Karger AG, Basel.

  11. A Meta Analysis and Hierarchical Classification of HU-Based Atherosclerotic Plaque Characterization Criteria

    NARCIS (Netherlands)

    Kristanto, Wisnumurti; van Ooijen, Peter M. A.; Jansen-van der Weide, Marijke C.; Vliegenthart, Rozemarijn; Oudkerk, Matthijs

    2013-01-01

    Background: Many computed tomography (CT) studies have reported that lipid-rich, presumably rupture-prone atherosclerotic plaques can be characterized according to their Hounsfield Unit (HU) value. However, the published HU-based characterization criteria vary considerably. The present study aims to

  12. Atherosclerotic plaque in carotid arteries in systemic lupus erythematosus: frequency and associated risk factors

    Directory of Open Access Journals (Sweden)

    Alexandre Wagner Silva de Souza

    Full Text Available CONTEXT AND OBJECTIVE: Atherosclerotic disease is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE patients. No previous study has estimated carotid disease prevalence in such patients in Brazil. The aim was to evaluate the prevalence of atherosclerotic plaque in carotid arteries, in SLE patients and controls, and to verify possible associations between risk factors and carotid plaque. DESIGN AND SETTING: Cross-sectional study, at Universidade Federal de São Paulo - Escola Paulista de Medicina. METHODS: Carotid plaque prevalence was assessed by B-mode ultrasound in 82 female SLE patients of mean age 34.0 years and 62 controls of mean age 35.7 years. Plaque was defined as a distinct area of hyperechogenicity and/or focal protrusion of the vessel wall into the lumen. Risk factors for coronary disease and SLE-related variables were determined. RESULTS: 50% of patients and 29% of controls presented carotid plaque. Older age, longer disease duration, higher Systemic Lupus International Collaborating Clinics (SLICC score, higher levels of low-density lipoprotein and greater diabetes, obesity, premature ovarian failure and family history of coronary artery disease were found in patients with carotid plaque than in those without plaque. Patients with plaque were younger than controls with plaque. SLE diagnosis, obesity, older age, higher SLICC score and longer disease duration were independent risk factors for carotid plaque. CONCLUSION: Young patients with SLE present higher prevalence of carotid plaque than controls. SLE diagnosis was a significant risk factor for carotid atherosclerosis.

  13. Atherosclerotic plaque delamination: Experiments and 2D finite element model to simulate plaque peeling in two strains of transgenic mice.

    Science.gov (United States)

    Merei, Bilal; Badel, Pierre; Davis, Lindsey; Sutton, Michael A; Avril, Stéphane; Lessner, Susan M

    2017-03-01

    Finite element analyses using cohesive zone models (CZM) can be used to predict the fracture of atherosclerotic plaques but this requires setting appropriate values of the model parameters. In this study, material parameters of a CZM were identified for the first time on two groups of mice (ApoE(-/-) and ApoE(-/-) Col8(-/-)) using the measured force-displacement curves acquired during delamination tests. To this end, a 2D finite-element model of each plaque was solved using an explicit integration scheme. Each constituent of the plaque was modeled with a neo-Hookean strain energy density function and a CZM was used for the interface. The model parameters were calibrated by minimizing the quadratic deviation between the experimental force displacement curves and the model predictions. The elastic parameter of the plaque and the CZM interfacial parameter were successfully identified for a cohort of 11 mice. The results revealed that only the elastic parameter was significantly different between the two groups, ApoE(-/-) Col8(-/-) plaques being less stiff than ApoE(-/-) plaques. Finally, this study demonstrated that a simple 2D finite element model with cohesive elements can reproduce fairly well the plaque peeling global response. Future work will focus on understanding the main biological determinants of regional and inter-individual variations of the material parameters used in the model. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  15. 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 (primary wavelength (≈1.0). Results suggest that, without flushing the luminal 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.

  16. 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.

  17. 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...... in the ground truth used for training: I) soft labels are created by Gaussian blurring of the original binary histology segmentations to reduce weights at the boundaries between components, and are weighted by the estimated registration accuracy of the histology and in vivo imaging data (measured by overlap...

  18. Tools for improving the diagnosis of atherosclerotic plaque using ultrasound

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

    , named ``XTRA'', has been designed, implemented, tested, and subsequently used for \\emph{in vitro} investigation of the MACI technique. The MACI method has been investigated on various tissue mimicking phantoms, on porcine tissue samples and on human carotid plaque specimens. Generally, the results show....... An increase of 30% in the axial width and 10% in the lateral width of the PSF was found, thus, the point resolution capability is only reduced marginally. Visualization of tissue interfaces was investigated using rubber tube phantoms, porcine aorta, and human plaque specimens. The MACI images show improved...... of eight regions were detectable when using MACI, compared to only three out of eight when using conventional B-mode imaging. Finally, two human carotid plaque specimens were scanned in 3D (by mechanical movement of the transducer in one direction). The MACI images were subjectively found to give a more...

  19. 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...... 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...

  20. Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel 18F-Folate Radiotracer

    Directory of Open Access Journals (Sweden)

    Adrienne Müller

    2014-03-01

    Full Text Available Folate receptor β (FR-β is overexpressed on activated, but not resting, macrophages involved in a variety of inflammatory and autoimmune diseases. A pivotal step in atherogenesis is the subendothelial accumulation of macrophages. In nascent lesions, they coordinate the scavenging of lipids and cellular debris to define the likelihood of plaque inflammation and eventually rupture. In this study, we determined the presence of FR-β-expressing macrophages in atherosclerotic lesions by the use of a fluorine-18-labeled folate-based radiotracer. Human endarterectomized specimens were used to measure gene expression levels of FR-β and CD68. Increased FR-β and CD68 levels were found in atherosclerotic plaques compared to normal artery walls by quantitative real-time polymerase chain reaction. Western blotting and immunohistochemistry demonstrated prominent FR-β protein levels in plaques. FR- β-positive cells colocalized with activated macrophages (CD68 in plaque tissue. Carotid sections incubated with 3′-aza-2′- [18F]fluorofolic acid displayed increased accumulation in atherosclerotic plaques through in vitro autoradiography. Specific binding of the radiotracer correlated with FR-β-expressing macrophages. These results demonstrate high FR-β expression in atherosclerotic lesions of human carotid tissue correlating with CD68-positive macrophages. Areas of high 3′-aza-2′-[18F]fluorofolic acid binding within the lesions represented FR-β-expressing macrophages. Selectively targeting FR-β-positive macrophages through folate-based radiopharmaceuticals may be useful for noninvasive imaging of plaque inflammation.

  1. Atherosclerotic disease in axial spondyloarthritis: increased frequency of carotid plaques.

    Science.gov (United States)

    Rueda-Gotor, Javier; Corrales, Alfonso; Blanco, Ricardo; Fuentevilla, Patricia; Portilla, Virginia; Expósito, Rosa; Mata, Cristina; Pina, Trinitario; González-Juanatey, Carlos; Llorca, Javier; González-Gay, Miguel A

    2015-01-01

    To establish whether subclinical atherosclerosis is increased in patients with axial spondyloarthritis (ax-SpA). A set of 149 consecutive patients with no history of cardiovascular disease that fulfilled the Assessment of SpondyloArthritis International Society classification criteria for ax-SpA was studied by carotid ultrasonography. Carotid intima-media thickness (cIMT) and plaques were assessed. A series of 181 community-based controls with no cardiovascular disease were studied for comparison. To establish whether ax-SpA might have a direct effect on the risk of carotid plaques or an indirect effect via its putative influence on hypertension, dyslipidaemia or obesity, we obtained adjusted odds ratios (OR) for each clinical factor by the development of adjusted models. cIMT was increased in patients (0.621±0.123 mm) when compared to controls (0.607±0.117 mm) but the difference was not significant (p=0.30). Nevertheless, carotid plaques were more commonly observed in patients with ax-SpA than in controls (41.6% vs. 26.4%; p=0.003). Patients with plaques had longer duration of the disease than those without plaques (20.5±11.2 years vs. 12.0±8.6 years; p<0.001). Plaques were more frequent in patients with hip involvement (crude odds ratio 3.15, 95% confidence interval [CI] 1.02-9.75; p=0.05), syndesmophytes (crude OR 4.94, 95% CI 2.14-11.4; p<0.001), in patients with higher functional limitation and mobility index measured by BASFI (crude OR 1.16, 95% CI 1.02-1.33; p=0.03) and BASMI (crude OR 1.45, 95% CI 1.19-1.77; p<0.001), and in those with psoriasis (crude OR 3.94, 95% CI 1.31-11.84; p=0.02. However, except for psoriasis that continued being a strong risk factor for plaques after adjustment, the relationship between other clinical features of ax-SpA and carotid plaques disappeared in the adjusted models. Our results confirm the presence of subclinical atherosclerosis in patients with ax-SpA.

  2. Induction of atherosclerotic plaque rupture in apolipoprotein E-/- mice after adenovirus-mediated transfer of p53

    NARCIS (Netherlands)

    Thüsen, J.H. von der; Vlijmen, B.J.M. van; Hoeben, R.C.; Kockx, M.M.; Havekes, L.M.; Berkel, T.J.C. van; Biessen, E.A.L.

    2002-01-01

    Background - The presence of the tumor-suppressor gene p53 in advanced atherosclerotic plaques and the sensitivity to p53-induced cell death of smooth muscle cells isolated from these plaques have fueled speculation about the role of p53 in lesion destabilization and plaque rupture. In this study,

  3. Amyloid plaque formation precedes dendritic spine loss.

    Science.gov (United States)

    Bittner, Tobias; Burgold, Steffen; Dorostkar, Mario M; Fuhrmann, Martin; Wegenast-Braun, Bettina M; Schmidt, Boris; Kretzschmar, Hans; Herms, Jochen

    2012-12-01

    Amyloid-beta plaque deposition represents a major neuropathological hallmark of Alzheimer's disease. While numerous studies have described dendritic spine loss in proximity to plaques, much less is known about the kinetics of these processes. In particular, the question as to whether synapse loss precedes or follows plaque formation remains unanswered. To address this question, and to learn more about the underlying kinetics, we simultaneously imaged amyloid plaque deposition and dendritic spine loss by applying two-photon in vivo microscopy through a cranial window in double transgenic APPPS1 mice. As a result, we first observed that the rate of dendritic spine loss in proximity to plaques is the same in both young and aged animals. However, plaque size only increased significantly in the young cohort, indicating that spine loss persists even many months after initial plaque appearance. Tracking the fate of individual spines revealed that net spine loss is caused by increased spine elimination, with the rate of spine formation remaining constant. Imaging of dendritic spines before and during plaque formation demonstrated that spine loss around plaques commences at least 4 weeks after initial plaque formation. In conclusion, spine loss occurs, shortly but with a significant time delay, after the birth of new plaques, and persists in the vicinity of amyloid plaques over many months. These findings hence give further hope to the possibility that there is a therapeutic window between initial amyloid plaque deposition and the onset of structural damage at spines.

  4. Dietary carnosine prevents early atherosclerotic lesion formation in apolipoprotein E-null mice.

    Science.gov (United States)

    Barski, Oleg A; Xie, Zhengzhi; Baba, Shahid P; Sithu, Srinivas D; Agarwal, Abhinav; Cai, Jian; Bhatnagar, Aruni; Srivastava, Sanjay

    2013-06-01

    Atherosclerotic lesions are associated with the accumulation of reactive aldehydes derived from oxidized lipids. Although inhibition of aldehyde metabolism has been shown to exacerbate atherosclerosis and enhance the accumulation of aldehyde-modified proteins in atherosclerotic plaques, no therapeutic interventions have been devised to prevent aldehyde accumulation in atherosclerotic lesions. We examined the efficacy of carnosine, a naturally occurring β-alanyl-histidine dipeptide, in preventing aldehyde toxicity and atherogenesis in apolipoprotein E-null mice. In vitro, carnosine reacted rapidly with lipid peroxidation-derived unsaturated aldehydes. Gas chromatography mass-spectrometry analysis showed that carnosine inhibits the formation of free aldehydes 4-hydroxynonenal and malonaldialdehyde in Cu(2+)-oxidized low-density lipoprotein. Preloading bone marrow-derived macrophages with cell-permeable carnosine analogs reduced 4-hydroxynonenal-induced apoptosis. Oral supplementation with octyl-D-carnosine decreased atherosclerotic lesion formation in aortic valves of apolipoprotein E-null mice and attenuated the accumulation of protein-acrolein, protein-4-hydroxyhexenal, and protein-4-hydroxynonenal adducts in atherosclerotic lesions, whereas urinary excretion of aldehydes as carnosine conjugates was increased. The results of this study suggest that carnosine inhibits atherogenesis by facilitating aldehyde removal from atherosclerotic lesions. Endogenous levels of carnosine may be important determinants of atherosclerotic lesion formation, and treatment with carnosine or related peptides could be a useful therapy for the prevention or the treatment of atherosclerosis.

  5. Multimodal nonlinear imaging of atherosclerotic plaques differentiation of triglyceride and cholesterol deposits

    Directory of Open Access Journals (Sweden)

    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.

  6. Safrole-2',3'-oxide induces atherosclerotic plaque vulnerability in apolipoprotein E-knockout mice.

    Science.gov (United States)

    Su, Le; Zhang, Haiyan; Zhao, Jing; Zhang, Shangli; Zhang, Yun; Zhao, Baoxiang; Miao, Junying

    2013-02-27

    Safrole-2',3'-oxide (SFO) is the major electrophilic metabolite of safrole (4-allyl-1, 2-methylenedioxybenzene), a natural plant constituent found in essential oils of numerous edible herbs and spices and in food containing these herbs, such as pesto sauce, cola beverages and bologna sausages. The effects of SFO in mammalian systems, especially the cardiovascular system, are little known. Disruption of vulnerable atherosclerotic plaques in atherosclerosis, a chronic inflammatory disease, is the main cause of cardiovascular events. In this study, we investigated SFO-induced atherosclerotic plaque vulnerability (possibility of rupture) in apolipoprotein E-knockout (apoE(-/-)) mice. Lipid area in vessel wall reached 59.8% in high dose SFO (SFO-HD) treated group, which is only 31.2% in control group. SFO treatment changed the lesion composition to an unstable phenotype, increased the number of apoptotic cells in plaque and the endothelium in plaques was damaged after SFO treatment. Furthermore, compared with control groups, the plaque endothelium level of p75(NTR) was 3-fold increased and the liver level of p75(NTR) was 17.4-fold increased by SFO-HD. Meanwhile, the serum level of KC (a functional homolog of IL-8 and the main proinflammatory alpha chemokine in mice) in apoE(-/-) mice was up to 357pg/ml in SFO-HD treated group. Thus, SFO contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating p75(NTR) and IL-8 and cell apoptosis in plaque. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. A Quantitative Model of Early Atherosclerotic Plaques Parameterized Using In Vitro Experiments.

    Science.gov (United States)

    Thon, Moritz P; Ford, Hugh Z; Gee, Michael W; Myerscough, Mary R

    2018-01-01

    There are a growing number of studies that model immunological processes in the artery wall that lead to the development of atherosclerotic plaques. However, few of these models use parameters that are obtained from experimental data even though data-driven models are vital if mathematical models are to become clinically relevant. We present the development and analysis of a quantitative mathematical model for the coupled inflammatory, lipid and macrophage dynamics in early atherosclerotic plaques. Our modeling approach is similar to the biologists' experimental approach where the bigger picture of atherosclerosis is put together from many smaller observations and findings from in vitro experiments. We first develop a series of three simpler submodels which are least-squares fitted to various in vitro experimental results from the literature. Subsequently, we use these three submodels to construct a quantitative model of the development of early atherosclerotic plaques. We perform a local sensitivity analysis of the model with respect to its parameters that identifies critical parameters and processes. Further, we present a systematic analysis of the long-term outcome of the model which produces a characterization of the stability of model plaques based on the rates of recruitment of low-density lipoproteins, high-density lipoproteins and macrophages. The analysis of the model suggests that further experimental work quantifying the different fates of macrophages as a function of cholesterol load and the balance between free cholesterol and cholesterol ester inside macrophages may give valuable insight into long-term atherosclerotic plaque outcomes. This model is an important step toward models applicable in a clinical setting.

  8. A rotational ablation tool for calcified atherosclerotic plaque removal.

    Science.gov (United States)

    Kim, Min-Hyeng; Kim, Hyung-Jung; Kim, Nicholas N; Yoon, Hae-Sung; Ahn, Sung-Hoon

    2011-12-01

    Atherosclerosis is a major cardiovascular disease involving accumulations of lipids, white blood cells, and other materials on the inside of artery walls. Since the calcification found in the advanced stage of atherosclerosis dramatically enhances the mechanical properties of the plaque, restoring the original lumen of the artery remains a challenge. High-speed rotational atherectomy, when performed with an ablating grinder to remove the plaque, produces much better results in the treatment of calcified plaque compared to other methods. However, the high-speed rotation of the Rotablator commercial rotational atherectomy device produces microcavitation, which should be avoided because of the serious complications it can cause. This research involves the development of a high-speed rotational ablation tool that does not generate microcavitation. It relies on surface modification to achieve the required surface roughness. The surface roughness of the tool for differential cutting was designed based on lubrication theory, and the surface of the tool was modified using Nd:YAG laser beam engraving. Electron microscope images and profiles indicated that the engraved surface of the tool had approximately 1 μm of root mean square surface roughness. The ablation experiment was performed on hydroxyapatite/polylactide composite with an elastic modulus similar to that of calcified plaque. In addition, differential cutting was verified on silicone rubber with an elastic modulus similar to that of a normal artery. The tool performance and reliability were evaluated by measuring the ablation force exerted, the size of the debris generated during ablation, and through visual inspection of the silicone rubber surface.

  9. Ultrasound-Based Carotid Elastography for Detection of Vulnerable Atherosclerotic Plaques Validated by Magnetic Resonance Imaging.

    Science.gov (United States)

    Huang, Chengwu; Pan, Xiaochang; He, Qiong; Huang, Manwei; Huang, Lingyun; Zhao, Xihai; Yuan, Chun; Bai, Jing; Luo, Jianwen

    2016-02-01

    Ultrasound-based carotid elastography has been developed to estimate the mechanical properties of atherosclerotic plaques. The objective of this study was to evaluate the in vivo capability of carotid elastography in vulnerable plaque detection using high-resolution magnetic resonance imaging as reference. Ultrasound radiofrequency data of 46 carotid plaques from 29 patients (74 ± 5 y old) were acquired and inter-frame axial strain was estimated with an optical flow method. The maximum value of absolute strain rate for each plaque was derived as an indicator for plaque classification. Magnetic resonance imaging of carotid arteries was performed on the same patients to classify the plaques into stable and vulnerable groups for carotid elastography validation. The maximum value of absolute strain rate was found to be significantly higher in vulnerable plaques (2.15 ± 0.79 s(-1), n = 27) than in stable plaques (1.21 ± 0.37 s(-1), n = 19) (p magnetic resonance imaging, was proven, revealing the potential of carotid elastography as an important tool in atherosclerosis assessment and stroke prevention. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  10. Divergent JAM-C Expression Accelerates Monocyte-Derived Cell Exit from Atherosclerotic Plaques.

    Directory of Open Access Journals (Sweden)

    Paul F Bradfield

    Full Text Available Atherosclerosis, caused in part by monocytes in plaques, continues to be a disease that afflicts the modern world. Whilst significant steps have been made in treating this chronic inflammatory disease, questions remain on how to prevent monocyte and macrophage accumulation in atherosclerotic plaques. Junctional Adhesion Molecule C (JAM-C expressed by vascular endothelium directs monocyte transendothelial migration in a unidirectional manner leading to increased inflammation. Here we show that interfering with JAM-C allows reverse-transendothelial migration of monocyte-derived cells, opening the way back out of the inflamed environment. To study the role of JAM-C in plaque regression we used a mouse model of atherosclerosis, and tested the impact of vascular JAM-C expression levels on monocyte reverse transendothelial migration using human cells. Studies in-vitro under inflammatory conditions revealed that overexpression or gene silencing of JAM-C in human endothelium exposed to flow resulted in higher rates of monocyte reverse-transendothelial migration, similar to antibody blockade. We then transplanted atherosclerotic, plaque-containing aortic arches from hyperlipidemic ApoE-/- mice into wild-type normolipidemic recipient mice. JAM-C blockade in the recipients induced greater emigration of monocyte-derived cells and further diminished the size of atherosclerotic plaques. Our findings have shown that JAM-C forms a one-way vascular barrier for leukocyte transendothelial migration only when present at homeostatic copy numbers. We have also shown that blocking JAM-C can reduce the number of atherogenic monocytes/macrophages in plaques by emigration, providing a novel therapeutic strategy for chronic inflammatory pathologies.

  11. Influence of insonification angle on echogenicity of B-mode images of atherosclerotic plaque in vitro

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Jespersen, Søren Kragh; Hansen, J. U.

    1998-01-01

    A newly developed (off-line) spatial compound scanner was used to scan formalin-fixed atherosclerotic carotid plaques. Forty-eight B-mode images were recorded using 7 insonification angles. All calculations were done on the envelope-detected image data. The mean amplitude level (MAL) in (relative......) volts was calculated for the plaque region in each image. The standard deviation over the 48 MAL values were for each of the 7 angles between 0.12 V and 0.18 V. For each scan plane, the standard deviation was also calculated over the 7 images. The mean and standard deviation of these 48 numbers were 0...

  12. Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR -/- mice.

    Science.gov (United States)

    Gajda, Mariusz; Jawień, Jacek; Mateuszuk, Lukasz; Lis, Grzegorz J; Radziszewski, Andrzej; Chłopicki, Stefan; Litwin, Jan A

    2008-01-01

    This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA), macrophages (rat anti-CD68) and T lymphocytes (rabbit anti-CD3). Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment.

  13. Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR -/- mice.

    Directory of Open Access Journals (Sweden)

    Stefan Chłopicki

    2008-06-01

    Full Text Available This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/- mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA, macrophages (rat anti-CD68 and T lymphocytes (rabbit anti-CD3. Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment.

  14. Research progress of noninvasive high - resolution magnetic resonance imaging in carotid atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Peng GAO

    2017-07-01

    Full Text Available Carotid atherosclerotic stenosis is closely related to recurrent ischemic stroke. Currently, therapies for carotid artery stenosis are mainly intensive medication or surgery, including carotid artery stenting (CAS and carotid endarterectomy (CEA. The prevention of stroke lies in identifying risk factors for carotid artery stenosis, screening patients with high risk of recurrent stroke, so as to benefit from medication or surgery. However, therapeutic schedule is formulated only according to the degrees of carotid artery stenosis, and there lacks of individualized treatment. Recently, new imaging modalities, such as noninvasive high.resolution MRI (HRMRI could detect the vulnerability of carotid atherosclerotic plaque. Compared with the degree of carotid artery stenosis measured by conventional DSA, noninvasive HRMRI can precisely predict the risk of ipsilateral stroke according to plaque morphology, so as to guide individualized treatment. DOI: 10.3969/j.issn.1672-6731.2017.05.012

  15. Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR -/- mice.

    OpenAIRE

    Stefan Chłopicki; Andrzej Radziszewski; Grzegorz J Lis; Lukasz Mateuszuk; Jacek Jawień; Mariusz Gajda; Jan A Litwin

    2008-01-01

    This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA), macrophages (rat anti-CD68) and T...

  16. The Immune Response Is Involved in Atherosclerotic Plaque Calcification: Could the RANKL/RANK/OPG System Be a Marker of Plaque Instability?

    Directory of Open Access Journals (Sweden)

    Fabrizio Montecucco

    2007-01-01

    Full Text Available Atherogenesis is characterized by an intense inflammatory process, involving immune and vascular cells. These cells play a crucial role in all phases of atherosclerotic plaque formation and complication through cytokine, protease, and prothrombotic factor secretion. The accumulation of inflammatory cells and thus high amounts of soluble mediators are responsible for the evolution of some plaques to instable phenotype which may lead to rupture. One condition strongly associated with plaque rupture is calcification, a physiopathological process orchestrated by several soluble factors, including the receptor activator of nuclear factor NFκB ligand (RANKL/receptor activator of nuclear factor NFκB (RANK/osteoprotegerin (OPG system. Although some studies showed some interesting correlations with acute ischemic events, at present, more evidences are needed to evaluate the predictive and diagnostic value of serum sRANKL and OPG levels for clinical use. The major limitation is probably the poor specificity of these factors for cardiovascular disease. The identification of tissue-specific isoforms could increase the importance of sRANKL and OPG in predicting calcified plaque rupture and the dramatic ischemic consequences in the brain and the heart.

  17. The association between Chlamydia pneumoniae DNA in atherosclerotic plaque and major risk factors in patients undergoing coronary artery bypass grafting

    NARCIS (Netherlands)

    Hedayat, Daryoosh Kamal; Jebeli, Mohammad; Mandegar, Mohammad Hossein; Bagheri, Jamshid; Nabavi, Seyed Abbas; Eghtesadi-Araghi, Payam; Mohammadzadeh, Robabeh; Darehzereshki, Ali; Chitsaz, Sam; Abbasi, Ali

    Background and aim: This study was conducted to investigate the prevalence of Chlamydia pneumoniae pathogen inside the atherosclerotic plaque of patients undergoing CABG by using PCR assay and to determine whether there is any association between the presence of bacteria in atherosclerotic lesions

  18. Ex vivo detection of macrophages in atherosclerotic plaques using intravascular ultrasonic-photoacoustic imaging

    Science.gov (United States)

    Quang Bui, Nhat; Hlaing, Kyu Kyu; Lee, Yong Wook; Kang, Hyun Wook; Oh, Junghwan

    2017-01-01

    Macrophages are excellent imaging targets for detecting atherosclerotic plaques as they are involved in all the developmental stages of atherosclerosis. However, no imaging technique is currently capable of visualizing macrophages inside blood vessel walls. The current study develops an intravascular ultrasonic-photoacoustic (IVUP) imaging system combined with indocyanine green (ICG) as a contrast agent to provide morphological and compositional information about the targeted samples. Both tissue-mimicking vessel phantoms and atherosclerotic plaque-mimicking porcine arterial tissues are used to demonstrate the feasibility of mapping macrophages labeled with ICG by endoscopically applying the proposed hybrid technique. A delay pulse triggering technique is able to sequentially acquire photoacoustic (PA) and ultrasound (US) signals from a single scan without using any external devices. The acquired PA and US signals are used to reconstruct 2D cross-sectional and 3D volumetric images of the entire tissue with the ICG-loaded macrophages injected. Due to high imaging contrast and sensitivity, the IVUP imaging vividly reveals structural information and detects the spatial distribution of the ICG-labeled macrophages inside the samples. ICG-assisted IVUP imaging can be a feasible imaging modality for the endoscopic detection of atherosclerotic plaques.

  19. Evaluating intensity normalization for multispectral classification of carotid atherosclerotic plaque

    Science.gov (United States)

    Gao, Shan; van't Klooster, Ronald; van Wijk, Diederik F.; Nederveen, Aart J.; Lelieveldt, Boudewijn P. F.; van der Geest, Rob J.

    2015-03-01

    Intensity normalization is an important preprocessing step for automatic plaque analysis in MR images as most segmentation algorithms require the images to have a standardized intensity range. In this study, we derived several intensity normalization approaches with inspiration from expert manual analysis protocols, for classification of carotid vessel wall plaque from in vivo multispectral MRI. We investigated intensity normalization based on a circular region centered at lumen (nCircle); based on sternocleidomastoid muscle (nSCM); based on intensity scaling (nScaling); based on manually classified fibrous tissue (nManuFibrous) and based on automatic classified fibrous tissue (nAutoFibrous). The proposed normalization methods were evaluated using three metrics: (1) Dice similarity coefficient (DSC) between manual and automatic segmentation obtained by classifiers using different normalizations; (2) correlation between proposed normalizations and normalization used by expert; (3) Mahalanobis Distance between pairs of components. In the performed classification experiments, features of normalized image, smoothed, gradient magnitude and Laplacian images at multi-scales, distance to lumen, distance to outer wall, wall thickness were calculated for each vessel wall (VW) pixel. A supervised pattern recognition system, based on a linear discriminate classifier, was trained using the manual segmentation result to classify each VW pixel to be one of the four classes: fibrous tissue, lipid, calcification, and loose matrix according to the highest posterior probability. We evaluated our method on image data of 23 patients. Compared to the result of conventional square region based intensity normalizatio n, nScaling resulted in significant increase in DSC for lipid (p = 0.006) and nAutoFibrous resulted in significant increase in DSC for calcification (p = 0.004). In conclusion, it was demonstrated that the conventional region based normalization approach is not optimal and n

  20. High-resolution intravascular magnetic resonance quantification of atherosclerotic plaque at 3T

    Directory of Open Access Journals (Sweden)

    Qian Di

    2012-03-01

    Full Text Available Abstract Background The thickness of fibrous caps (FCT of atherosclerotic lesions is a critical factor affecting plaque vulnerability to rupture. This study tests whether 3 Tesla high-resolution intravascular cardiovascular magnetic resonance (CMR employing tiny loopless detectors can identify lesions and accurately measure FCT in human arterial specimens, and whether such an approach is feasible in vivo using animal models. Methods Receive-only 2.2 mm and 0.8 mm diameter intravascular loopless CMR detectors were fabricated for a clinical 3 Tesla MR scanner, and the absolute signal-to-noise ratio determined. The detectors were applied in a two-step protocol comprised of CMR angiography to identify atherosclerotic lesions, followed by high-resolution CMR to characterize FCT, lesion size, and/or vessel wall thickness. The protocol was applied in fresh human iliac and carotid artery specimens in a human-equivalent saline bath. Mean FCT measured by 80 μm intravascular CMR was compared with histology of the same sections. In vivo studies compared aortic wall thickness and plaque size in healthy and hyperlipidemic rabbit models, with post-mortem histology. Results Histology confirmed plaques in human specimens, with calcifications appearing as signal voids. Mean FCT agreed with histological measurements within 13% on average (correlation coefficient, R = 0.98; Bland-Altman analysis, -1.3 ± 68.9 μm. In vivo aortic wall and plaque size measured by 80 μm intravascular CMR agreed with histology. Conclusion Intravascular 3T CMR with loopless detectors can both locate atherosclerotic lesions, and accurately measure FCT at high-resolution in a strategy that appears feasible in vivo. The approach shows promise for quantifying vulnerable plaque for evaluating experimental therapies.

  1. Vitamin K-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype.

    Directory of Open Access Journals (Sweden)

    Leon J Schurgers

    Full Text Available Vitamin K-antagonists (VKA are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE(-/- model of atherosclerosis.A total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD. VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE(-/- mice (10 weeks received a Western type diet (WTD for 12 weeks, after which mice were fed a WTD supplemented with vitamin K(1 (VK(1, 1.5 mg/g or vitamin K(1 and warfarin (VK(1&W; 1.5 mg/g & 3.0 mg/g for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden.VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE(-/- mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle.

  2. {sup 18}F-FDG in distinction of atherosclerotic plaque: Innovation in PET/MRI technology

    Energy Technology Data Exchange (ETDEWEB)

    Benedetto, Raquel; Fonseca, Lea Mirian Barbosa da, E-mail: benedettoraquel@yahoo.com.b [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Carneiro, Michel Pontes; Junqueira, Flavia Albuquerque; Coutinho Junior, Antonio [Clinica de Diagnostico por Imagem (CDPI), Rio de Janeiro, RJ (Brazil); Ristow, Arno von [Centervasc, Rio de Janeiro, RJ (Brazil)

    2009-12-15

    The glucose analogue, {sup 18}F-FDG, can be used to image inflammatory cell activity non-invasively by PET. In the present study, we investigate the possibility of using {sup 18}F-FDG to characterize atherosclerotic plaques. A 77-year-old man with symptomatic carotid atherosclerosis was imaged using {sup 18}F-FDG-PET and co-registered MRI. A plaque with intense fibrotic and necrotic content was obtained. Due to the fact that the tissue showed up as inactive, according to the metabolic activity, it was not possible to observe {sup 18}F-FDG uptake. Our aim was to confirm that it could be clinically used to predict the inflammatory activity of the plaque. (author)

  3. 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...

  4. Simultaneous Non-contrast Angiography and intraPlaque hemorrhage (SNaP) imaging for carotid atherosclerotic disease evaluation

    NARCIS (Netherlands)

    Wang, J.; Boernert, P.; Zhao, H.; Hippe, D.; Xihai Zhao; Balu, N.; Ferguson, M.S.; Hatsukami, T.S.; Xu, J.; Yuan, C.; Kerwin, W.S.

    2012-01-01

    A Simultaneous Non-contrast Angiography and intraPlaque hemorrhage (SNAP) MR imaging technique was proposed to detect both luminal stenosis and hemorrhage in atherosclerosis patients in a single scan. 13patients with diagnosed carotid atherosclerotic plaque were recruited after informed consent. All

  5. Digital Image Analysis of Ultrasound B-mode images of Carotid Atherosclerotic Plaque: Correlation with Histological Examination

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Rosendal, Kim; Grønholdt, Marie-Louise Moes

    1996-01-01

    This paper reports on a study of how well texture features extracted from B-mode images of atherosclerotic plaque correlates with histological results obtained from the same plaque after carotid endarterectomy. The study reveals that a few second order texture features (diagonal moment, standard...

  6. Near-infrared autofluorescence induced by intraplaque hemorrhage and heme degradation as marker for high-risk atherosclerotic plaques.

    Science.gov (United States)

    Htun, Nay Min; Chen, Yung Chih; Lim, Bock; Schiller, Tara; Maghzal, Ghassan J; Huang, Alex L; Elgass, Kirstin D; Rivera, Jennifer; Schneider, Hans G; Wood, Bayden R; Stocker, Roland; Peter, Karlheinz

    2017-07-13

    Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients.Atherosclerosis diagnosis relies primarily on imaging and early detection of high-risk atherosclerotic plaques is important for risk stratification of patients and stabilization therapies. Here Htun et al. demonstrate that vulnerable atherosclerotic plaques generate near-infrared autofluorescence that can be detected via emission computed tomography.

  7. Non-calcified coronary atherosclerotic plaque visualization on CT : effects of contrast-enhancement and lipid-content fractions

    NARCIS (Netherlands)

    Kristanto, Wisnumurti; van Ooijen, Peter M. A.; Greuter, Marcel J. W.; Groen, Jaap M.; Vliegenthart, Rozemarijn; Oudkerk, Matthijs

    Computed tomography (CT) may characterize lipid-rich and presumably rupture-prone non-calcified coronary atherosclerotic plaque based on its Hounsfield-Unit (HU), but still inconclusively. This study aimed to evaluate factors influencing the HU-value of non-calcified plaque using software

  8. Fluorescence imaging of macrophages in atherosclerotic plaques using plasmonic gold nanorose

    Science.gov (United States)

    Wang, Tianyi; Sapozhnikova, Veronika; Mancuso, J. Jacob; Willsey, Brian; Qiu, Jinze; Ma, Li L.; Li, Xiankai; Johnston, Keith P.; Feldman, Marc D.; Milner, Thomas E.

    2011-03-01

    Macrophages are one of the most important cell types involved in the progression of atherosclerosis which can lead to myocardial infarction. To detect macrophages in atherosclerotic plaques, plasmonic gold nanorose is introduced as a nontoxic contrast agent for fluorescence imaging. We report macrophage cell culture and ex vivo tissue studies to visualize macrophages targeted by nanorose using scanning confocal microscopy. Atherosclerotic lesions were created in the aorta of a New Zealand white rabbit model subjected to a high cholesterol diet and double balloon injury. The rabbit was injected with nanoroses coated with dextran. A HeNe laser at 633 nm was used as an excitation light source and a acousto-optical beam splitter was utilized to collect fluorescence emission in 650-760 nm spectral range. Results of scanning confocal microscopy of macrophage cell culture and ex vivo tissue showed that nanoroses produce a strong fluorescence signal. The presence of nanorose in ex vivo tissue was further confirmed by photothermal wave imaging. These results suggest that scanning confocal microscopy can identify the presence and location of nanorose-loaded macrophages in atherosclerotic plaques.

  9. Inducible reduction in pregnancy-associated plasma protein-A gene expression inhibits established atherosclerotic plaque progression in mice.

    Science.gov (United States)

    Bale, Laurie K; Chakraborty, Suban; Conover, Cheryl A

    2014-04-01

    Pregnancy-associated plasma protein-A (PAPP-A) is a novel zinc metalloproteinase implicated in cardiovascular disease. The aim of this study was to determine whether a reduction in PAPP-A expression in the adult affects the progression of established atherosclerotic plaque. Apolipoprotein E-null mice were fed a high-fat diet for 5 weeks to initiate early-stage plaque development before tamoxifen-inducible, Cre recombinase-mediated excision of the floxed PAPP-A gene. High-fat feeding was continued, and after 10 weeks the aorta and brachiocephalic artery were harvested for atherosclerotic plaque analyses of overall burden and morphology, respectively. An inducible decrease in PAPP-A gene expression significantly inhibited atherosclerotic plaque progression as assessed by a 70% reduction in plaque burden in the aorta (P = .012) without an effect on the elevated circulating levels of cholesterol and triglycerides in this model. Furthermore, this reduction in PAPP-A prevented the development of advanced plaque with necrotic cores and buried fibrous caps in the brachiocephalic artery. These data indicate PAPP-A as a potential target to limit progression of established atherosclerotic plaque.

  10. Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy.

    Directory of Open Access Journals (Sweden)

    Abigail S Haka

    Full Text Available The progressive accumulation of monocyte-derived cells in the atherosclerotic plaque is a hallmark of atherosclerosis. However, it is now appreciated that monocytes represent a heterogeneous circulating population of cells that differ in functionality. New approaches are needed to investigate the role of monocyte subpopulations in atherosclerosis since a detailed understanding of their differential mobilization, recruitment, survival and emigration during atherogenesis is of particular importance for development of successful therapeutic strategies. We present a novel methodology for the in vivo examination of monocyte subpopulations in mouse models of atherosclerosis. This approach combines cellular labeling by fluorescent beads with multiphoton microscopy to visualize and monitor monocyte subpopulations in living animals. First, we show that multiphoton microscopy is an accurate and timesaving technique to analyze monocyte subpopulation trafficking and localization in plaques in excised tissues. Next, we demonstrate that multiphoton microscopy can be used to monitor monocyte subpopulation trafficking in atherosclerotic plaques in living animals. This novel methodology should have broad applications and facilitate new insights into the pathogenesis of atherosclerosis and other inflammatory diseases.

  11. Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy.

    Science.gov (United States)

    Haka, Abigail S; Potteaux, Stephane; Fraser, Haley; Randolph, Gwendalyn J; Maxfield, Frederick R

    2012-01-01

    The progressive accumulation of monocyte-derived cells in the atherosclerotic plaque is a hallmark of atherosclerosis. However, it is now appreciated that monocytes represent a heterogeneous circulating population of cells that differ in functionality. New approaches are needed to investigate the role of monocyte subpopulations in atherosclerosis since a detailed understanding of their differential mobilization, recruitment, survival and emigration during atherogenesis is of particular importance for development of successful therapeutic strategies. We present a novel methodology for the in vivo examination of monocyte subpopulations in mouse models of atherosclerosis. This approach combines cellular labeling by fluorescent beads with multiphoton microscopy to visualize and monitor monocyte subpopulations in living animals. First, we show that multiphoton microscopy is an accurate and timesaving technique to analyze monocyte subpopulation trafficking and localization in plaques in excised tissues. Next, we demonstrate that multiphoton microscopy can be used to monitor monocyte subpopulation trafficking in atherosclerotic plaques in living animals. This novel methodology should have broad applications and facilitate new insights into the pathogenesis of atherosclerosis and other inflammatory diseases.

  12. An integrated method for atherosclerotic carotid plaque segmentation in ultrasound image.

    Science.gov (United States)

    Qian, Chunjun; Yang, Xiaoping

    2018-01-01

    Carotid artery atherosclerosis is an important cause of stroke. Ultrasound imaging has been widely used in the diagnosis of atherosclerosis. Therefore, segmenting atherosclerotic carotid plaque in ultrasound image is an important task. Accurate plaque segmentation is helpful for the measurement of carotid plaque burden. In this paper, we propose and evaluate a novel learning-based integrated framework for plaque segmentation. In our study, four different classification algorithms, along with the auto-context iterative algorithm, were employed to effectively integrate features from ultrasound images and later also the iteratively estimated and refined probability maps together for pixel-wise classification. The four classification algorithms were support vector machine with linear kernel, support vector machine with radial basis function kernel, AdaBoost and random forest. The plaque segmentation was implemented in the generated probability map. The performance of the four different learning-based plaque segmentation methods was tested on 29 B-mode ultrasound images. The evaluation indices for our proposed methods were consisted of sensitivity, specificity, Dice similarity coefficient, overlap index, error of area, absolute error of area, point-to-point distance, and Hausdorff point-to-point distance, along with the area under the ROC curve. The segmentation method integrated the random forest and an auto-context model obtained the best results (sensitivity 80.4 ± 8.4%, specificity 96.5 ± 2.0%, Dice similarity coefficient 81.0 ± 4.1%, overlap index 68.3 ± 5.8%, error of area -1.02 ± 18.3%, absolute error of area 14.7 ± 10.9%, point-to-point distance 0.34 ± 0.10 mm, Hausdorff point-to-point distance 1.75 ± 1.02 mm, and area under the ROC curve 0.897), which were almost the best, compared with that from the existed methods. Our proposed learning-based integrated framework investigated in this study could be useful for

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

    Science.gov (United States)

    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

    2014-08-01

    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. 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. 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. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Protein corona and phospholipase activity drive selective accumulation of nanomicelles in atherosclerotic plaques.

    Science.gov (United States)

    Lechuga-Vieco, Ana V; Groult, Hugo; Pellico, Juan; Mateo, Jesús; Enríquez, Jose A; Ruiz-Cabello, Jesús; Herranz, Fernando

    2018-01-06

    ApoB-100 and Phosphatidylcholine-specific phospholipase C (PC-PLC) are important contributors to atherosclerosis development. ApoB-100 is the main structural protein of LDL, being directly associated with atherosclerosis plaque generation. PC-PLC is highly expressed in atherosclerosis lesions and contributes to their progression. We show how phosphatidylcholine-coated nanomicelles can be used for specific characterisation of atherosclerosis plaque. Results show that ApoB-100 in the protein corona of the nanomicelle targets the particles to atherosclerotic areas in apolipoprotein E -/- mice. Furthermore, PC-PLC selectively removes the polar heads from the phospholipid coating of the nanomicelles leading to their accumulation. To fully characterise the behaviour of the nanomicelles, we developed multimodal probes using a nanoemulsion step. Hybrid imaging revealed plaque accumulation of the nanomicelles and colocalisation with PC-PLC expression and ApoB-100 in the plaque. This study shows how protein corona composition and enzyme-driven nanomaterial accumulation can be used for detection of atherosclerosis. Copyright © 2018. Published by Elsevier Inc.

  15. Evidence for contribution of the y chromosome in atherosclerotic plaque occurrence in men.

    Science.gov (United States)

    Voskarides, Konstantinos; Hadjipanagi, Despina; Papazachariou, Louiza; Griffin, Maura; Panayiotou, Andrie G

    2014-08-01

    Diseases such as atherosclerosis and coronary artery disease demonstrate disparate population prevalence or present with variable severity in men and women. While the usual explanation points to hormonal status, the role of the Y chromosome has been implicated, but not sufficiently studied. We genotyped six markers of the male-specific region of the Y chromosome, representing the major haplogroups (YAP, G, I, J, K, and R) in 373 male participants of the "Cyprus Study" with ultrasonic data on subclinical atherosclerosis. Of the five major haplogroups identified, two (J and K) accounted for roughly 67% of the Y-chromosome variance among these Greek Cypriot men. Carriers of haplogroup K had a 2.5-fold higher age-adjusted risk for having an atherosclerotic plaque present in any of the four bifurcations scanned, compared to men with other Y-chromosome lineages (OR=2.51; 95% CI=1.18 to 5.33; p=0.017). Carriers of the YAP haplogroup had about 50% less risk for having a plaque in the femoral bifurcation versus the rest (OR=0.46; 95% CI=0.27 to 0.77; p<0.001). We show a possible contribution of the Y chromosome in atherosclerotic phenotypes in men adding to the previous findings for coronary artery disease. Additional studies are warranted as evidence suggests that the Y chromosome could serve as a biomarker for the health status of men.

  16. KLF4 Dependent Phenotypic Modulation of SMCs Plays a Key Role in Atherosclerotic Plaque Pathogenesis

    Science.gov (United States)

    Shankman, Laura S.; Gomez, Delphine; Cherepanova, Olga A.; Salmon, Morgan; Alencar, Gabriel F.; Haskins, Ryan M.; Swiatlowska, Pamela; Newman, Alexandra A. C.; Greene, Elizabeth S.; Straub, Adam C.; Isakson, Brant; Randolph, Gwendalyn J.; Owens, Gary K.

    2015-01-01

    Herein we employ Myh11-CreERT2 ROSA floxed STOP eYFP Apoe−/− smooth muscle cell (SMC) lineage tracing mice to show that traditional methods for detecting SMCs based on immuno-staining fail to detect > 80% of SMC-derived cells within advanced atherosclerotic lesions. These unidentified SMC-derived cells exhibit phenotypes of other cell lineages including macrophages (Mϕs), and mesenchymal stem cells (MSCs). SMC-specific conditional knockout (KO) of Krüppel-like factor 4 (KLF4) resulted in reduced numbers of SMC-derived MSC-, and Mϕ-like cells, marked reductions in lesion size, and increases in multiple indices of plaque stability, including an increase in fibrous cap thickness. Results of in vivo KLF4 ChIP-Seq analyses, and studies in cultured SMC treated with cholesterol identified > 800 KLF4 target genes including many that regulate pro-inflammatory responses of SMC. Results indicate that the contribution of SMCs within atherosclerotic plaques has been greatly underestimated, and that KLF4-dependent transitions in SMC phenotype are critical in lesion pathogenesis. PMID:25985364

  17. Preliminary in vivo atherosclerotic carotid plaque characterization using the accumulated axial strain and relative lateral shift strain indices

    Science.gov (United States)

    Shi, Hairong; Mitchell, Carol C.; McCormick, Matthew; Kliewer, Mark A.; Dempsey, Robert J.; Varghese, Tomy

    2008-11-01

    In this paper, we explore two parameters or strain indices related to plaque deformation during the cardiac cycle, namely, the maximum accumulated axial strain in plaque and the relative lateral shifts between plaque and vessel wall under in vivo clinical ultrasound imaging conditions for possible identification of vulnerable plaque. These strain indices enable differentiation between calcified and lipidic plaque tissue utilizing a new perspective based on the stiffness and mobility of the plaque. In addition, they also provide the ability to distinguish between softer plaques that undergo large deformations during the cardiac cycle when compared to stiffer plaque tissue. Soft plaques that undergo large deformations over the cardiac cycle are more prone to rupture and to release micro-emboli into the cerebral bloodstream. The ability to identify vulnerable plaque, prone to rupture, would significantly enhance the clinical utility of this method for screening patients. We present preliminary in vivo results obtained from ultrasound radio frequency data collected over 16 atherosclerotic plaque patients before these patients undergo a carotid endarterectomy procedure. Our preliminary in vivo results indicate that the maximum accumulated axial strain over a cardiac cycle and the maximum relative lateral shift or displacement of the plaque are useful strain indices that provide differentiation between soft and calcified plaques.

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

    Science.gov (United States)

    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.

  19. Expression of the vitamin K-dependent proteins GAS6 and protein S and the TAM receptor tyrosine kinases in human atherosclerotic carotid plaques.

    Science.gov (United States)

    Hurtado, B; Muñoz, X; Recarte-Pelz, P; García, N; Luque, A; Krupinski, J; Sala, N; García de Frutos, P

    2011-05-01

    The GAS6/ProS-TAM system is composed of two vitamin K-dependent ligands (GAS6 and protein S) and their three protein tyrosine kinase receptors TYRO3, AXL and MERTK, known as the TAM receptors. The system plays a prominent role in conditions of injury, inflammation and repair. In murine models of atherosclerotic plaque formation, mutations in its components affect atherosclerosis severity. Here we used Taqman low-density arrays and immunoblotting to study mRNA and protein expression of GAS6, ProS and the TAM receptors in human carotid arteries with different degrees of atherosclerosis. The results show a clear down-regulation of the expression of AXL in atheroma plaques with respect to normal carotids that is matched by decreased abundance of AXL in protein extracts detected by immunoblotting. A similar decrease was observed in PROS1 mRNA expression in atherosclerotic carotids compared to the normal ones, but in this case protein S (ProS) was clearly increased in protein extracts of carotid arteries with increasing grade of atherosclerosis, suggesting that ProS is carried into the plaque. MERTK was also increased in atherosclerotic carotid arteries with respect to the normal ones, suggesting that the ProS-MERTK axis is functional in advanced human atherosclerotic plaques. MERTK was expressed in macrophages, frequently in association with ProS, while ProS was abundant also in the necrotic core. Our data suggest that the ProS-MERTK ligand-receptor pair was active in advanced stages of atherosclerosis, while AXL signalling is probably down-regulated.

  20. Delineation of atherosclerotic plaque using subharmonic imaging filtering techniques and a commercial intravascular ultrasound system.

    Science.gov (United States)

    Sridharan, Anush; Eisenbrey, John R; Machado, Priscilla; deMuinck, Ebo D; Doyley, Marvin M; Forsberg, Flemming

    2013-01-01

    The ability to delineate atherosclerotic plaque from the surrounding tissue using custom-developed subharmonic imaging (SHI) digital filtering techniques was investigated in vivo using a commercially available system. Atherosclerosis was induced in the aorta of two Watanabe Heritable Hyperlipidemic rabbits following which injections of an ultrasound contrast agent (UCA) Definity (Lantheus Medical Imaging, N Billerica, Massachusetts) were administered. Imaging was performed using a Galaxy intravascular ultrasound (IVUS) scanner (Boston Scientific, Natick, Massachusetts) equipped with an Atlantis® SR Pro Imaging Catheter (Boston Scientific). Four preliminary band-pass filters were designed to isolate the subharmonic signal (from surrounding tissue) and applied to the radio-frequency (RF) data. Preliminary filter performances were compared in terms of vessel-tissue contrast-to-tissue ratio (CTR) and visual examination. Based on preliminary results, a subharmonic adaptive filter and a stopband (SB) filter were designed and applied to the RF data. Images were classified as fundamental, SHI, and SB. Four readers performed qualitative analysis of 168 randomly selected images (across all three imaging modes). The images were scored for overall image quality, image noise, plaque visualization, and vessel lumen visualization. A Wilcoxon signed-rank test was used to compare the scores followed by intraclass correlation (ICC) evaluation. Quantitative analysis was performed by calculating the CTRs for the vessel-to-plaque and vessel-to-tissue (compared using a paired student's t test). Qualitative analysis showed SHI and SB to have significantly less image noise relative to the fundamental mode (p < 0.001). Fundamental mode scored significantly higher than SHI and SB for the remaining three categories. ICC showed mixed results among reader evaluation for delineation of plaque. However, quantitatively, SHI produced the best vessel-plaque CTR.

  1. Atherosclerotic plaque ultrasound video encoding, wireless transmission, and quality assessment using H.264.

    Science.gov (United States)

    Panayides, A; Pattichis, M S; Pattichis, Constantinos S; Loizou, C P; Pantziaris, M; Pitsillides, Andreas

    2011-05-01

    We propose a unifying framework for efficient encoding, transmission, and quality assessment of atherosclerotic plaque ultrasound video. The approach is based on a spatially varying encoding scheme, where video-slice quantization parameters are varied as a function of diagnostic significance. Video slices are automatically set based on a segmentation algorithm. They are then encoded using a modified version of H.264/AVC flexible macroblock ordering (FMO) technique that allows variable quality slice encoding and redundant slices (RSs) for resilience over error-prone transmission channels. We evaluate our scheme on a representative collection of ten ultrasound videos of the carotid artery for packet loss rates up to 30%. Extensive simulations incorporating three FMO encoding methods, different quantization parameters, and different packet loss scenarios are investigated. Quality assessment is based on a new clinical rating system that provides independent evaluations of the different parts of the video (subjective). We also use objective video-quality assessment metrics and estimate their correlation to the clinical quality assessment of plaque type. We find that some objective quality assessment measures computed over the plaque video slices gave very good correlations to mean opinion scores (MOSs). Here, MOSs were computed using two medical experts. Experimental results show that the proposed method achieves enhanced performance in noisy environments, while at the same time achieving significant bandwidth demands reductions, providing transmission over 3G (and beyond) wireless networks.

  2. Combined acoustic-photoacoustic and fluorescence imaging catheter for the detection of the atherosclerotic plaque

    Science.gov (United States)

    Abran, Maxime; Matteau-Pelletier, Carl; Zerouali-Boukhal, Karim; Tardif, Jean-Claude; Lesage, Frédéric

    2011-03-01

    In industrialized countries, cardiovascular diseases remain the main cause of mortality. The detection of atherosclerosis and its associated plaque using imaging techniques allows studying the efficacy of new drugs in vivo. Intravascular ultrasound (IVUS) imaging has been demonstrated to be a powerful tool to uncover structural information of atherosclerotic plaques. Recently, intravascular photoacoustic (IVPA) has been combined with IVUS imaging to add functional and/or molecular information. The IVPA/IVUS combination has been demonstrated in phantoms and ex vivo tissues to provide relevant information about the composition of the plaque, as well as its vulnerability. In this work, we extend previous work by developing a combined IVPA/IVUS system using a rotating ultrasound transducer in a catheter to which an optical fiber is attached. In addition, a third modality was included through fluorescence detection in the same fiber at a distinct wavelength from PA, opening the door to complementary information using fluorescence activatable probes. Cylindrical silicon phantoms with inclusions containing fluorophores or ink were used to validate the system. Bleaching of the fluorophore by the pulsed laser used for photoacoustic was quantified. IVUS images were obtained continuously and used to co-register photoacoustic and fluorescence signals.

  3. 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.

  4. Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.

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    Kurt Reifenberg

    Full Text Available Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1 and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE(-/- mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet as indicated by aortic plaque area en face (p<0.05. Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD, significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD, significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.

  5. [Theoretical thinking on relationship between toxic-stasis pathogenicity and atherosclerotic vulnerable plaque].

    Science.gov (United States)

    Zhang, Jing-Chun; Chen, Ke-Ji

    2008-04-01

    Vulnerable plaque rupture is the main cause of acute coronary syndrome (ACS), a representative cardiovascular thrombotic disease. Considering that the Western medical pathogenetic recognition on vulnerable plaque inflammatory reaction and thrombus formation is similar to the etiopathogenesis and clinical characteristics of toxin and stasis as well as the clinical manifestation of toxic-stasis in TCM, the authors believe that it is necessary to expand the previous TCM thinking on taking blood stasis as the main etiopathogenesis for ACS to that ACS is caused by the toxic-stasis induced vulnerable plaque rupture. Therefore to make sense, depending evidence-based medical principle, the relationship between toxic-stasis and vulnerable plaque forming and rupturing, and to form the clinical norm for diagnosis and treatment of toxic-stasis should be helpful for the prevention and control of ACS.

  6. 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

  7. Correction of lumen contrast-enhancement influence on non-calcified coronary atherosclerotic plaque quantification on CT

    NARCIS (Netherlands)

    Kristanto, Wisnumurti; Tuncay, Volkan; Vliegenthart, Rozemarijn; van Ooijen, Peter M. A.; Oudkerk, Matthijs

    Lumen contrast-enhancement influences non-calcified atherosclerotic plaque Hounsfield-unit (HU) values in computed tomography (CT). This study aimed to construct and validate an algorithm to correct for this influence. Three coronary vessel phantoms with 1, 2, and 4 mm circular hollow lumina; with

  8. 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

  9. The presence of some cytokines and Chlamydia pneumoniae in the atherosclerotic carotid plaque in patients with carotid artery stenosis

    Directory of Open Access Journals (Sweden)

    Dariusz Janczak

    2015-02-01

    Full Text Available Background: Over the last few years the role of microorganisms in the pathogenesis of atherosclerosis has been widely discussed. Chlamydia pneumoniae activates immune cells to produce cytokines that are responsible for the formation of atheromatous carotid lesions.Material and methods: The study was carried out at the Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, in 2002-2003, on 100 consecutive symptomatic patients with internal carotid stenosis, who underwent an endarterectomy procedure. Each patient had their carotid artery sampled in order to find C. pneumoniae DNA using the nested PCR method and some cytokines (TGF-β, VEGF, FGF, TNF-α using immunohistochemical examination. The control group consisted of 20 young organ donors who had been diagnosed with brain death and who had their healthy carotid artery harvested. Analogous genetic and immunohistochemical tests were performed.Results: We did not confirm the presence of either cytokines or C. pneumoniae in the healthy carotid arteries. The presence of FGF was probably due to intima fibroblast activity, which is responsible for elastin and collagen synthesis for the extracellular matrix. C. pneumoniae was discovered in 68% of patients with carotid plaques. Three cytokines (TGF-β, FGF, TNF-α were detected in atherosclerotic internal carotid arteries as well.Conclusion: Chronic infection by C. pneumoniae may exacerbate carotid plaque development and may lead to its destabilization.

  10. Bilateral symmetry of local inflammatory activation in human carotid atherosclerotic plaques.

    Science.gov (United States)

    Benetos, Georgios; Toutouzas, Konstantinos; Drakopoulou, Maria; Tolis, Elias; Masoura, Constantina; Nikolaou, Charalampia; Tsekoura, Dorothea; Tsiamis, Eleftherios; Grassos, Harris; Siores, Elias; Stefanadis, Christodoulos; Tousoulis, Dimitris

    2015-01-01

    Only a few studies have investigated the structural and functional characteristics of carotid arteries bilaterally. Furthermore, there is controversy as to whether inflammation in paired vascular beds is a local or systemic phenomenon. We aimed to examine, in patients with coronary artery disease, whether intra-subject left and right carotid arteries have similar inflammatory status, as determined non-invasively by microwave radiometry (MWR). Consecutive patients (n=200) with significant coronary artery disease were evaluated via an ultrasound echo-colour Doppler (US-ECD) study of both carotid arteries and temperature measurements with MWR. During thermography, thermal heterogeneity (ΔT) was defined as the maximum temperature along the carotid artery minus the minimum temperature. Mean T was similar between the left and right carotid arteries (0.78 ± 0.48 vs. 0.84 ± 0.52°C, p=0.12). Mean right intima-media thickness (IMT) was greater compared to mean left IMT (2.16 ± 1.20 vs. 1.93 ± 0.94 mm, p<0.01). In all carotids, there was a correlation between left and right carotid plaque ΔT (R=0.38, p<0.001) and between left and right IMT (R=0.48, p<0.001). Independent predictors for the presence of bilateral carotid plaques were found to be the extent of coronary artery disease, high ΔT, and therapy with angiotensin II receptor blockers; predictors for the presence of high ΔT bilaterally were bilateral carotid plaques, male sex, diabetes mellitus, and hypertension. There is bilateral inflammatory activation in the carotid atherosclerotic lesions of patients with coronary artery disease. At this stage of carotid disease, arterial hypertension and diabetes mellitus are more strongly correlated with bilateral functional abnormalities in carotid plaques than with structural changes.

  11. ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis.

    Science.gov (United States)

    Zhang, Yue Hui; Hao, Qing Qing; Wang, Xiao Yu; Chen, Xu; Wang, Nan; Zhu, Li; Li, Shu Ying; Yu, Qing Tao; Dong, Bo

    2015-06-01

    Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied. Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated. Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity. The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway. © The Author(s) 2014.

  12. Potent Vasoconstrictor Kisspeptin-10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist.

    Science.gov (United States)

    Sato, Kengo; Shirai, Remina; Hontani, Mina; Shinooka, Rina; Hasegawa, Akinori; Kichise, Tomoki; Yamashita, Tomoyuki; Yoshizawa, Hayami; Watanabe, Rena; Matsuyama, Taka-Aki; Ishibashi-Ueda, Hatsue; Koba, Shinji; Kobayashi, Youichi; Hirano, Tsutomu; Watanabe, Takuya

    2017-04-14

    Kisspeptin-10 (KP-10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor, GPR54, have currently received much attention in relation to pre-eclampsia. However, it still remains unknown whether KP-10 could affect atherogenesis. We evaluated the effects of KP-10 on human umbilical vein endothelial cells, human monocyte-derived macrophages, human aortic smooth muscle cells in vitro, and atherosclerotic lesions in apolipoprotein E-deficient (ApoE-/-) mice in vivo. KP-10 significantly increased the adhesion of human monocytes to human umbilical vein endothelial cells, which was significantly inhibited by pretreatment with P234, a GPR54 antagonist. KP-10 stimulated mRNA expression of tumor necrosis factor-α, interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin in human umbilical vein endothelial cells. KP-10 significantly enhanced oxidized low-density lipoprotein-induced foam cell formation associated with upregulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in human monocyte-derived macrophages. In human aortic smooth muscle cells, KP-10 significantly suppressed angiotensin II-induced migration and proliferation, but enhanced apoptosis and activities of matrix metalloproteinase (MMP)-2 and MMP-9 by upregulation of extracellular signal-regulated kinase 1 and 2, p38, Bcl-2-associated X protein, and caspase-3. Four-week-infusion of KP-10 into ApoE-/- mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration and vascular inflammation as well as decreased intraplaque vascular smooth muscle cells contents. Proatherosclerotic effects of endogenous and exogenous KP-10 were completely canceled by P234 infusion in ApoE-/- mice. Our results suggest that KP-10 may contribute to accelerate the progression and instability of atheromatous plaques, leading to plaque rupture. The GPR54 antagonist may be

  13. Atherosclerotic plaque identification by virtual histology intravascular ultrasound in a rabbit abdominal aorta model of vulnerable plaque.

    Science.gov (United States)

    Lin, Qing-Fei; Luo, Yu-Kun; Zhao, Zi-Wen; Cai, Wei; Zhen, Xing-Chun; Chen, Liang-Long

    2013-11-01

    This study aimed to evaluate the utility of virtual histology intravascular ultrasound (VH-IVUS) for recognizing vulnerable plaque compared to histological pathological analysis. Four-month-old New Zealand rabbits (n = 16) were randomly divided into two groups: one fed a high-fat diet and subjected to balloon injury (experimental, n = 10) and one fed a high-fat diet alone (control, n = 6). Blood lipid profiles of overnight-fasted rabbits were measured at week 2 (beginning of study) and week 12 (end of study). At week 12, experimental group rabbits underwent IVUS under anaesthesia. Rabbits were sacrificed and a 5-cm segment of the abdominal aorta was removed. Arterial sections were subjected to pathological and immunohistochemical analyses. Serum lipid levels increased in all rabbits fed with high-fat diet, with low-density lipid cholesterol (LDL-C) levels increasing the most. Levels of six biomarkers (high sensitivity C-reactive protein, matrix metalloproteinase-3, interleukin [IL]-1, IL-10, tumour necrosis factor-α, and oxidized [ox]-LDL) showed no differences between the two groups at week 2, but were higher in the experimental group at week 12. A total of 276 atherosclerotic plaques in the experimental group were analysed. VH-IVUS had sensitivities of 87% and 92% for detection of noncalcified and calcified thin-cap fibroatheromas, respectively. VH-IVUS correctly identified 85% and 89% of noncalcified and calcified fibroatheromas, respectively. For detection of pathological intimal thickening, VH-IVUS showed a sensitivity of 79% and positive predictive value of 78%. Linear regression analysis showed a strong correlation between histology and VH-IVUS for the percent area of fibrous fibro-fatty tissue, necrotic calcified tissue, and confluent necrotic core. The intra-observer and inter-observer variability of the intimal and medial-adventitial boundaries was low. Endothelial injury followed by a high-fat diet in rabbits is a viable method for inducing

  14. Effect of sexual steroids on the calcium content of aortic atherosclerotic plaque of oophorectomized rabbits

    Directory of Open Access Journals (Sweden)

    J.M. Aldrighi

    2005-05-01

    Full Text Available We determined the effect of conjugated equine estrogen plus medroxyprogesterone acetate on calcium content of aortic atherosclerotic lesions in oophorectomized adult New Zealand rabbits submitted to a cholesterol rich diet. Five groups of 10 animals each were studied: G1 = control, G2 = cholesterol diet only, G3 = diet plus conjugated equine estrogen (0.625 mg/day; G4 and G5 = diet, conjugated equine estrogen (0.625 mg/day plus medroxyprogesterone acetate (5 and 10 mg/day, respectively. Mean weight varied from 2.7 ± 0.27 to 3.1 ± 0.20 kg (P = 0.38 between groups at the beginning and 3.1 ± 0.27 to 3.5 ± 0.20 kg (P = 0.35 at the end of the experiment. Cholesterol and triglyceride levels were determined at the time of oophorectomy, 21 days after surgery (time 0, and at the end of follow-up of 90 days. The planimetric method was used to measure plaque and caryometric method for histopathologic examination of the aorta. Calcium content was determined by the method of von Kossa. A similar increase in cholesterol occurred in all treated groups without differences between them at the end of the study. Groups G4 and G5 had smaller areas of atherosclerotic lesions (2.33 ± 2.8 and 2.45 ± 2.1 cm², respectively than the groups receiving no progestogens (G2: 5.6 ± 4 and G3: 4.6 ± 2.8 cm²; P = 0.02. The relation between lesion area and total aorta area was smaller in groups treated with combined drugs compared to the groups receiving no progesterone (G4: 14.9 ± 13 and G5: 14.2 ± 13.4 vs G2: 35.8 ± 26 and G3: 25 ± 8 cm², respectively; P = 0.017. Oral conjugated equine estrogen (0.625 mg/day plus medroxyprogesterone acetate (5 or 10 mg/day provoked a greater reduction in atherosclerotic plaque area and calcium content in treated groups, suggesting a dose-dependent effect.

  15. Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by Regulating NF-κB Dependent Matrix Metalloproteinase-9 Expression via LPA2 in Macrophages

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    Xi Chen

    2017-04-01

    Full Text Available Lysophosphatidic acid (LPA, one of the simplest phospholipid signaling molecules, participates in formation and disruption of atherosclerotic plaque. Matrix metalloproteinases (MMPs contribute to atherosclerotic plaque rupture by involving in extracellular matrix (ECM degradation and then thinning fibrous cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated with coronary plaque instability, but the relationship between LPA and MMP-9 remains unclear. The present work therefore aimed at elucidating association between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in macrophages. We found that plasma LPA and MMP-9 levels were correlated positively (r = 0.31, P < 0.05 and both elevated significantly in patients with acute myocardial infarct (AMI. Consistent with peripheral blood levels, histochemical staining indicated that autotaxin (ATX, LPA-producing ectoenzyme, and MMP-9 were expressed frequently in the necrotic core and fibrous cap of human unstable plaques, which might increase the instability of plaque. Experiments in vitro were done with THP-1-derived macrophages and showed that LPA enhanced the expression, secretion and activity of MMP-9 in a time- and dose-dependent manner. Induction of LPA on pro-MMP-9 and active-MMP-9 was confirmed in human peripheral blood monocyte-derived macrophages. PDTC, NF-κB inhibitor, but not inhibitor of AP-1 and PPARγ, effectively prevented LPA-induced MMP-9 expression and NF-κB p65 siRNA decreased MMP-9 transcription, confirming that LPA might induce MMP-9 elevation by activating NF-κB pathway. In addition, knockdown of LPA2 attenuated LPA-induced MMP-9 expression and nucleus p65 levels. These findings revealed that LPA upregulated the expression of MMP-9 through activating NF-κB pathway in the LPA2 dependent manner, hence blocking LPA receptors signaling may provide therapeutic strategy to target plaque destabilization.

  16. Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice

    Science.gov (United States)

    Alexander, Matthew R.; Moehle, Christopher W.; Johnson, Jason L.; Yang, Zhengyu; Lee, Jae K.; Jackson, Christopher L.; Owens, Gary K.

    2011-01-01

    Clinical complications of atherosclerosis arise primarily as a result of luminal obstruction due to atherosclerotic plaque growth, with inadequate outward vessel remodeling and plaque destabilization leading to rupture. IL-1 is a proinflammatory cytokine that promotes atherogenesis in animal models, but its role in plaque destabilization and outward vessel remodeling is unclear. The studies presented herein show that advanced atherosclerotic plaques in mice lacking both IL-1 receptor type I and apolipoprotein E (Il1r1–/–Apoe–/– mice) unexpectedly exhibited multiple features of plaque instability as compared with those of Il1r1+/+Apoe–/– mice. These features included reduced plaque SMC content and coverage, reduced plaque collagen content, and increased intraplaque hemorrhage. In addition, the brachiocephalic arteries of Il1r1–/–Apoe–/– mice exhibited no difference in plaque size, but reduced vessel area and lumen size relative to controls, demonstrating a reduction in outward vessel remodeling. Interestingly, expression of MMP3 was dramatically reduced within the plaque and vessel wall of Il1r1–/–Apoe–/– mice, and Mmp3–/–Apoe–/– mice showed defective outward vessel remodeling compared with controls. In addition, MMP3 was required for IL-1–induced SMC invasion of Matrigel in vitro. Taken together, these results show that IL-1 signaling plays a surprising dual protective role in advanced atherosclerosis by promoting outward vessel remodeling and enhancing features of plaque stability, at least in part through MMP3-dependent mechanisms. PMID:22201681

  17. Echo-lucency of computerized ultrasound images of carotid atherosclerotic plaques are associated with increased levels of triglyceride-rich lipoproteins as well as increased plaque lipid content

    DEFF Research Database (Denmark)

    Grønholdt, Marie-Louise Moes; Nordestgaard, Børge G.; Weibe, Brit M.

    1998-01-01

    Background-Echo-lucency of carotid atherosclerotic plaques on computerized ultrasound B-mode images has been associated with a high incidence of brain infarcts as evaluated on CT scans. We tested the hypotheses that triglyceride-rich lipoproteins in the fasting and postprandial state predict...... computer processed to yield a measure of echogenicity (gray-scale level). Lipoproteins were measured before and hourly ibr 4 hours after a standardized fatty meal, A subgroup of 58 patients underwent endarterectomy. On linear regression analysis, echu-lucency (low gray-scale level) was associated......-rich lipoproteins predict echo-lucency of carotid plaques, which is associated with increased plaque Lipid content, Because echo-lucency has been associated with a high incidence of brain infarcts on CT scans, triglyceride-rich lipoproteins may predict a plaque type particularly vulnerable to rupture....

  18. Echolucency of computerized ultrasound images of carotid atherosclerotic plaques are associated with increased levels of triglyceride-rich lipoproteins as well as increased plaque lipid content

    DEFF Research Database (Denmark)

    Grønholdt, Marie-Louise M.; Nordestgaard, Børge; Wiebe, Britt M.

    1998-01-01

    Background-Echo-lucency of carotid atherosclerotic plaques on computerized ultrasound B-mode images has been associated with a high incidence of brain infarcts as evaluated on CT scans. We tested the hypotheses that triglyceride-rich lipoproteins in the fasting and postprandial state predict...... computer processed to yield a measure of echogenicity (gray-scale level). Lipoproteins were measured before and hourly ibr 4 hours after a standardized fatty meal, A subgroup of 58 patients underwent endarterectomy. On linear regression analysis, echu-lucency (low gray-scale level) was associated......-rich lipoproteins predict echo-lucency of carotid plaques, which is associated with increased plaque Lipid content, Because echo-lucency has been associated with a high incidence of brain infarcts on CT scans, triglyceride-rich lipoproteins may predict a plaque type particularly vulnerable to rupture....

  19. Characterization of atherosclerotic plaque by reflection spectroscopy and thermography: a comparison

    Science.gov (United States)

    Lilledahl, Magnus B.; Haugen, Olav A.; Randeberg, Lise L.; Svaasand, Lars O.

    2005-04-01

    Many methods for detecting and measuring vulnerable atherosclerotic plaques have been proposed. These include reflection spectroscopy, thermography, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). This paper presents an analysis and a comparison of two of these methods, near-infrared reflection spectroscopy (NIRS) and thermography. Most of the published literature evaluate methods statistically. A more analytic approach will make it easier to compare the different methods and determine if the measured signal will be strong enough in a real measurement situation. This is the approach taken in this article. Eight samples of human aorta were examined by NIRS and subsequently prepared for histology. A total of 28 measurement points were selected. A measure of the lipid content based on reflection spectra is proposed. Comparisons of this lipid measure with histology show that the lipid content in the plaques yields relatively small changes in the value of this lipid-index. Reflectance spectra from models based on the diffusion approximation for total reflectance were simulated. Temperature measurements were performed on three Watanabe heritable hyperlipidemic (WHHL) rabbits and one New Zealand white (NZW) rabbit with a thermistor-type intravascular temperature sensor. The measurements gave no significant signals which correlated with the subsequent histology. A simple analytic model was developed which indicates that a temperature increase of more than 0.01-0.04 °C at the surface of a vessel wall, due to inflammation in a plaque, is unlikely. Such a small temperature difference will probably be obscured by normal variation in the vessel wall temperature.

  20. Pregnancy associated plasma protein-A (PAPP-A) is not a marker of the vulnerable atherosclerotic plaque.

    Science.gov (United States)

    Iversen, Kasper; Teisner, Ane; Dalager, Soren; Olsen, Karen Ege; Floridon, Charlotte; Teisner, Børge

    2011-03-01

    To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A. Vulnerable plaques and control tissues were examined by immunohistochemistry. Volunteers and patients with non-atherosclerotic disease were examined for release of PAPP-A during ischemia and medical treatment. Non-atherosclerotic tissue samples were examined after incubation with heparins. We were not able to detect PAPP-A in vulnerable plaques. Patients and volunteers experiencing ischemic events without atherosclerotic lesions only had elevated PAPP-A when treated with heparin. When tissue from normal artery wall was incubated with heparin, PAPP-A was eluted. This was not the case for non-arterial tissue samples. Elevation of PAPP-A in patients with acute coronary syndromes seems to be caused by heparin induced release of PAPP-A from the arterial wall and not due to excretion from vulnerable plaques. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin.

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    Chunmei Qi

    Full Text Available Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA modified ultra-small super paramagnetic iron oxide (USPIO was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI.Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30. Group A with atherosclerosis plaque (n = 10 were controls. VP was established in groups B (n = 10 and C (n = 10 using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured.DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05.After successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.

  3. In vivo detection of activated platelets allows characterizing rupture of atherosclerotic plaques with molecular magnetic resonance imaging in mice.

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    Dominik von Elverfeldt

    Full Text Available BACKGROUND: Early and non-invasive detection of platelets on micro atherothrombosis provides a means to identify unstable plaque and thereby allowing prophylactic treatment towards prevention of stroke or myocardial infarction. Molecular magnetic resonance imaging (mMRI of activated platelets as early markers of plaque rupture using targeted contrast agents is a promising strategy. In this study, we aim to specifically image activated platelets in murine atherothrombosis by in vivo mMRI, using a dedicated animal model of plaque rupture. METHODS: An antibody targeting ligand-induced binding sites (LIBS on the glycoprotein IIb/IIIa-receptor of activated platelets was conjugated to microparticles of iron oxide (MPIO to form the LIBS-MPIO contrast agent causing a signal-extinction in T2*-weighted MRI. ApoE(-/- mice (60 weeks-old were fed a high fat diet for 5 weeks. Using a small needle, the surface of their carotid plaques was scratched under blood flow to induce atherothrombosis. In vivo 9.4 Tesla MRI was performed before and repetitively after intravenous injection of either LIBS-MPIO versus non-targeted-MPIO. RESULTS: LIBS-MPIO injected animals showed a significant signal extinction (p<0.05 in MRI, corresponding to the site of plaque rupture and atherothrombosis in histology. The signal attenuation was effective for atherothrombosis occupying ≥ 2% of the vascular lumen. Histology further confirmed significant binding of LIBS-MPIO compared to control-MPIO on the thrombus developing on the surface of ruptured plaques (p<0.01. CONCLUSION: in vivo mMRI detected activated platelets on mechanically ruptured atherosclerotic plaques in ApoE(-/- mice with a high sensititvity. This imaging technology represents a unique opportunity for noninvasive detection of atherothrombosis and the identification of unstable atherosclerotic plaques with the ultimate promise to prevent strokes and myocardial infarctions.

  4. Tiaozhi Tongmai Granules reduce atherogenesis and promote the expression of ATP-binding cassette transporter A1 in rabbit atherosclerotic plaque macrophages and the liver

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    Qing Sun

    2014-07-01

    Conclusions: Tiaozhi Tongmai Granules appear to have an anti-atherogenic effect that is most likely mediated by simultaneously upregulating the protein expression of ABCA1 in rabbit atherosclerotic plaque macrophages and in the liver.

  5. Cadmium exposure and atherosclerotic carotid plaques –Results from the Malmö diet and Cancer study

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. A tissue-engineered 3D model of light scattering in atherosclerotic plaques

    Science.gov (United States)

    Levitz, David; Hinds, Monica T.; Wang, Ruikang K.; Ma, Zhenhe; Ishii, Katsu; Tran, Noi; McCarty, Owen J. T.; Hanson, Stephen R.; Jacques, Steven L.

    2007-02-01

    The development of atherosclerotic plaques includes changes in the cellular and extracellular composition of the arterial wall. Although these changes in composition affect the manner in which light scatters in the vessel wall and thus affect any optical signal, experimentally determining how features of atherosclerosis affect optical signals has remained elusive. Using current tissue-engineering methods, we developed a 3D tissue construct model for assessing how certain features of atherosclerosis (the increased concentrations of lipids and macrophages) affect optical signals. The model is based on vascular tissue constructs made of smooth muscle cells (SMCs) and macrophages (M\\Fgr s) that are co-cultured inside a 3D scaffold matrix of collagen fibers with interspersed lipids. To make the scaffold matrix, powdered collagen was dissolved in acetic acid, homogenized, and neutralized by sequential dialyses to yield a soft gel of 2 μm thick collagen fibers in which cells were seeded. In "normal" constructs, only SMCs were seeded in the collagen gel; in "athero-like" constructs, both SMCs and M\\Fgr s (loaded or unloaded with lipid) were seeded in the gel. To demonstrate the use of this model, sets of slab-shaped normal and athero-like constructs were imaged by optical coherence tomography (OCT) and qualitatively analyzed. 2D frames from 3D OCT image cubes were compared to 2D histology sections. Our results indicate that the cellular composition of the construct affects morphological features of the OCT image.

  7. Chlamydia pneumoniae in the atherosclerotic plaques of coronary artery disease patients.

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    Morteza Izadi

    2013-12-01

    Full Text Available An association between Chlamydia pneumoniae (C. pneumoniae and cardiovascular disease has been demonstrated. In this study, we aimed to study this potential relationship in 105 Iranian patients. Coronary artery specimens from 105 Iranian patients undergoing CABG were analyzed by PCR method for C. pneumoniae. Serological evaluation for C. pneumoniae IgG and IgM was performed using ELISA. 53 specimens from mamillary artery were also investigated. C. pneumoniae PCR test result was positive for 23 (21.9% of patients with coronary artery atherosclerosis, but none of the specimens from the mamillary artery was positive for C. pneumoniae when it was evaluated by the PCR (P<0.001. Coronary artery disease patients with and without a history of unstable angina or myocardial infarction were comparable in C. pneumoniae PCR test positive rates (P=0.618. Relevance of IgG and IgM positivity were also studied by correlating it to the study parameters, but no difference was found. CRP was significantly higher in the IgM positive group (P<0.001. A significant proportion of coronary atherosclerotic plaques are infected with C. pneumoniae while no infection was found in the normal mamillary artery specimens. No association was found between acute coronary syndromes and serological and PCR positivity. Further prospective randomized controlled studies with large patient population are needed to confirm our findings.

  8. Topographic association of angioscopic yellow plaques with coronary atherosclerotic plaque: assessment with quantitative colorimetry in human coronary artery autopsy specimens.

    Science.gov (United States)

    Ishibashi, Fumiyuki; Lisauskas, Jennifer B; Kawamura, Akio; Waxman, Sergio

    2008-01-01

    Yellow plaques seen during coronary angioscopy are thought to be the surrogates for superficial intimal lipids in coronary plaque. Given diffuse and heterogeneous nature of atherosclerosis, yellow plaques in coronaries may be seen as several yellow spots on diffuse coronary plaque. We examined the topographic association of yellow plaques with coronary plaque. In 40 non-severely stenotic ex-vivo coronary segments (average length: 52.2 +/- 3.1 mm), yellow plaques were examined by angioscopy with quantitative colorimetry. The segments were cut perpendicular to the long axis of the vessel at 2 mm intervals, and 1045 slides with 5 microm thick tissue for whole segments were prepared. To construct the plaque surface, each tissue slice was considered to be representative of the adjacent 2 mm. The circumference of the lumen and the lumen border of plaque were measured in each slide, and the plaque surface region was constructed. Coronary plaque was in 37 (93%) of 40 segments, and consisted of a single mass [39.9 +/- 3.9 (0-100) mm, 311.3 +/- 47.4 (0.0-1336.2) mm2]. In 30 (75%) segments, multiple (2-9) yellow plaques were detected on a mass of coronary plaque. The number of yellow plaques correlated positively with coronary plaque surface area (r = 0.77, P colorimetry, some of them are associated with lipid cores underneath thin fibrous caps, may be used to assess the extent of coronary plaque. Further research using angioscopy could be of value to study the association of high-risk coronaries with acute coronary syndromes.

  9. Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae

    NARCIS (Netherlands)

    de Boer, O. J.; van der Wal, A. C.; Houtkamp, M. A.; Ossewaarde, J. M.; Teeling, P.; Becker, A. E.

    2000-01-01

    OBJECTIVE: Atherosclerotic lesions are characterized by an immune mediated chronic inflammation. Seroepidemiological studies support a relationship between atherosclerotic disease and infection with C. pneumoniae; an association further endorsed by immunocytochemical and DNA directed studies.

  10. Exposure to Cigarette Smoke and the Morphology of Atherosclerotic Plaques in the Extracranial Arteries Assessed by Computed Tomography Angiography in Patients with Essential Hypertension.

    Science.gov (United States)

    Gać, Paweł; Jaźwiec, Przemysław; Mazur, Grzegorz; Poręba, Rafał

    2017-01-01

    The aim of the study was to determine the relationship between exposure to cigarette smoke and the morphology of atherosclerotic plaques in the extracranial arteries assessed by computed tomography angiography in patients with hypertension. The study included 61 hypertensive patients: 17 active smokers (group A), 18 non-smokers, declaring environmental exposure to tobacco smoke (group B), and 26 non-smokers, not declaring exposure to cigarette smoke (group C). The number of segments with plaques was significantly higher in group A compared to groups B and C. The number of segments with non-calcified and mixed plaques was significantly higher in group A and group B than in group C. A positive correlation between cigarette-years and the number of segments with atherosclerotic plaques was noted. In summary, both active smoking and environmental exposure to tobacco smoke appear to increase the number of segments of the extracranial arteries with non-calcified and mixed atherosclerotic plaques.

  11. Stabilizing role of platelet P2Y(12 receptors in shear-dependent thrombus formation on ruptured plaques.

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    Reyhan Nergiz-Unal

    Full Text Available BACKGROUND: In most models of experimental thrombosis, healthy blood vessels are damaged. This results in the formation of a platelet thrombus that is stabilized by ADP signaling via P2Y(12 receptors. However, such models do not predict involvement of P2Y(12 in the clinically relevant situation of thrombosis upon rupture of atherosclerotic plaques. We investigated the role of P2Y(12 in thrombus formation on (collagen-containing atherosclerotic plaques in vitro and in vivo, by using a novel mouse model of atherothrombosis. METHODOLOGY: Plaques in the carotid arteries from Apoe(-/- mice were acutely ruptured by ultrasound treatment, and the thrombotic process was monitored via intravital fluorescence microscopy. Thrombus formation in vitro was assessed in mouse and human blood perfused over collagen or plaque material under variable conditions of shear rate and coagulation. Effects of two reversible P2Y(12 blockers, ticagrelor (AZD6140 and cangrelor (AR-C69931MX, were investigated. PRINCIPAL FINDINGS: Acute plaque rupture by ultrasound treatment provoked rapid formation of non-occlusive thrombi, which were smaller in size and unstable in the presence of P2Y(12 blockers. In vitro, when mouse or human blood was perfused over collagen or atherosclerotic plaque material, blockage or deficiency of P2Y(12 reduced the thrombi and increased embolization events. These P2Y(12 effects were present at shear rates >500 s(-1, and they persisted in the presence of coagulation. P2Y(12-dependent thrombus stabilization was accompanied by increased fibrin(ogen binding. CONCLUSIONS/SIGNIFICANCE: Platelet P2Y(12 receptors play a crucial role in the stabilization of thrombi formed on atherosclerotic plaques. This P2Y(12 function is restricted to high shear flow conditions, and is preserved in the presence of coagulation.

  12. Targeted Inhibition of Pregnancy-Associated Plasma Protein-A Activity Reduces Atherosclerotic Plaque Burden in Mice.

    Science.gov (United States)

    Conover, Cheryl A; Bale, Laurie K; Oxvig, Claus

    2016-02-01

    The metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A), has been implicated in the development of cardiovascular disease in humans and mouse models. In the latter, genetic deletion or overexpression of PAPP-A confirmed a major role for PAPP-A in atherosclerosis. In this study, we tested the hypothesis that targeting PAPP-A proteolytic activity by an inhibitory monoclonal antibody (mAb-PA) reduces atherosclerotic plaque progression. Apolipoprotein E knock-out mice on high-fat diet were treated with mAb-PA or isotype control. Control mice had a 10-fold increase in aortic plaque after 10 weeks. Aortic plaque burden was reduced by ∼ 70% in mice treated with mAb-PA (P = 0.0002). Treatment was efficacious even in the face of elevated cholesterol and triglycerides. This study demonstrates proof-of-principle and provides feasibility for a novel therapeutic strategy to inhibit atherosclerotic plaque burden by selective targeting of PAPP-A.

  13. Calculation of arterial wall temperature in atherosclerotic arteries: effect of pulsatile flow, arterial geometry, and plaque structure

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    Kim Taehong

    2007-03-01

    Full Text Available Abstract Background This paper presents calculations of the temperature distribution in an atherosclerotic plaque experiencing an inflammatory process; it analyzes the presence of hot spots in the plaque region and their relationship to blood flow, arterial geometry, and inflammatory cell distribution. Determination of the plaque temperature has become an important topic because plaques showing a temperature inhomogeneity have a higher likelihood of rupture. As a result, monitoring plaque temperature and knowing the factors affecting it can help in the prevention of sudden rupture. Methods The transient temperature profile in inflamed atherosclerotic plaques is calculated by solving an energy equation and the Navier-Stokes equations in 2D idealized arterial models of a bending artery and an arterial bifurcation. For obtaining the numerical solution, the commercial package COMSOL 3.2 was used. The calculations correspond to a parametric study where arterial type and size, as well as plaque geometry and composition, are varied. These calculations are used to analyze the contribution of different factors affecting arterial wall temperature measurements. The main factors considered are the metabolic heat production of inflammatory cells, atherosclerotic plaque length lp, inflammatory cell layer length lmp, and inflammatory cell layer thickness dmp. Results The calculations indicate that the best location to perform the temperature measurement is at the back region of the plaque (0.5 ≤ l/lp ≤ 0.7. The location of the maximum temperature, or hot spot, at the plaque surface can move during the cardiac cycle depending on the arterial geometry and is a direct result of the blood flow pattern. For the bending artery, the hot spot moves 0.6 millimeters along the longitudinal direction; for the arterial bifurcation, the hot spot is concentrated at a single location due to the flow recirculation observed at both ends of the plaque. Focusing on the

  14. Synthesis of acid-stabilized iron oxide nanoparticles and comparison for targeting atherosclerotic plaques: evaluation by MRI, quantitative MPS, and TEM alternative to ambiguous Prussian blue iron staining.

    Science.gov (United States)

    Scharlach, Constantin; Kratz, Harald; Wiekhorst, Frank; Warmuth, Carsten; Schnorr, Jörg; Genter, Gesche; Ebert, Monika; Mueller, Susanne; Schellenberger, Eyk

    2015-07-01

    To further optimize citrate-stabilized VSOPs (very small iron oxide particles, developed for MR angiography) for identification of atherosclerotic plaques, we modified their surface during synthesis using eight other acids for electrostatic stabilization. This approach preserves effective production for clinical application. Five particles were suitable to be investigated in targeting plaques of apoE(-/-) mice. Accumulation was evaluated by ex vivo MRI, TEM, and quantitatively by magnetic particle spectroscopy (MPS). Citric- (VSOP), etidronic-, tartaric-, and malic-acid-coated particles accumulated in atherosclerotic plaques with highest accumulation for VSOP (0.2‰ of injected dose). Targets were phagolysosomes of macrophages and of altered endothelial cells. In vivo MRI with VSOP allowed for definite plaque identification. Prussian blue staining revealed abundant endogenous iron in plaques, indistinguishable from particle iron. In apoE(-/-) mice, VSOPs are still the best anionic iron oxide particles for imaging atherosclerotic plaques. MPS allows for quantification of superparamagnetic nanoparticles in such small specimens. The presence of vulnerable plaques in arteries is important for the prediction of acute coronary events. VSOP (very small iron oxide particles, developed for MR angiography) have been shown to be very sensitive in identifying atherosclerotic plaques. The authors studied here further modification to the surface of VSOP during synthesis and compared their efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Phenotype commitment in vascular smooth muscle cells derived from coronary atherosclerotic plaques: differential gene expression of endothelial Nitric Oxide Synthase

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    ML Rossi

    2009-06-01

    Full Text Available Unstable angina and myocardial infarction are the clinical manifestations of the abrupt thrombotic occlusion of an epicardial coronary artery as a result of spontaneous atherosclerotic plaque rupture or fissuring, and the exposure of highly thrombogenic material to blood. It has been demonstrated that the proliferation of vascular smooth muscle cells (VSMCs and impaired bioavailabilty of nitric oxide (NO are among the most important mechanisms involved in the progression of atherosclerosis. It has also been suggested that a NO imbalance in coronary arteries may be involved in myocardial ischemia as a result of vasomotor dysfunction triggering plaque rupture and the thrombotic response. We used 5’ nuclease assays (TaqMan™ PCRs to study gene expression in coronary plaques collected by means of therapeutic directional coronary atherectomy from 15 patients with stable angina (SA and 15 with acute coronary syndromes (ACS without ST elevation. Total RNA was extracted from the 30 plaques and the cDNA was amplified in order to determine endothelial nitric oxide synthase (eNOS gene expression. Analysis of the results showed that the expression of eNOS was significantly higher (p<0.001 in the plaques from the ACS patients. Furthermore, isolated VSMCs from ACS and SA plaques confirmed the above pattern even after 25 plating passages. In situ RT-PCR was also carried out to co-localize the eNOS messengers and the VSMC phenotype.

  16. Joint learning of ultrasonic backscattering statistical physics and signal confidence primal for characterizing atherosclerotic plaques using intravascular ultrasound.

    Science.gov (United States)

    Sheet, Debdoot; Karamalis, Athanasios; Eslami, Abouzar; Noël, Peter; Chatterjee, Jyotirmoy; Ray, Ajoy K; Laine, Andrew F; Carlier, Stephane G; Navab, Nassir; Katouzian, Amin

    2014-01-01

    Intravascular Ultrasound (IVUS) is a predominant imaging modality in interventional cardiology. It provides real-time cross-sectional images of arteries and assists clinicians to infer about atherosclerotic plaques composition. These plaques are heterogeneous in nature and constitute fibrous tissue, lipid deposits and calcifications. Each of these tissues backscatter ultrasonic pulses and are associated with a characteristic intensity in B-mode IVUS image. However, clinicians are challenged when colocated heterogeneous tissue backscatter mixed signals appearing as non-unique intensity patterns in B-mode IVUS image. Tissue characterization algorithms have been developed to assist clinicians to identify such heterogeneous tissues and assess plaque vulnerability. In this paper, we propose a novel technique coined as Stochastic Driven Histology (SDH) that is able to provide information about co-located heterogeneous tissues. It employs learning of tissue specific ultrasonic backscattering statistical physics and signal confidence primal from labeled data for predicting heterogeneous tissue composition in plaques. We employ a random forest for the purpose of learning such a primal using sparsely labeled and noisy samples. In clinical deployment, the posterior prediction of different lesions constituting the plaque is estimated. Folded cross-validation experiments have been performed with 53 plaques indicating high concurrence with traditional tissue histology. On the wider horizon, this framework enables learning of tissue-energy interaction statistical physics and can be leveraged for promising clinical applications requiring tissue characterization beyond the application demonstrated in this paper. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. SPECT/CT Imaging of High-Risk Atherosclerotic Plaques using Integrin-Binding RGD Dimer Peptides.

    Science.gov (United States)

    Yoo, Jung Sun; Lee, Jonghwan; Jung, Jae Ho; Moon, Byung Seok; Kim, Soonhag; Lee, Byung Chul; Kim, Sang Eun

    2015-06-30

    Vulnerable atherosclerotic plaques with unique biological signatures are responsible for most major cardiovascular events including acute myocardial infarction and stroke. However, current clinical diagnostic approaches for atherosclerosis focus on anatomical measurements such as the degree of luminal stenosis and wall thickness. An abundance of neovessels with elevated expression of integrin αvβ3 is closely associated with an increased risk of plaque rupture. Herein we evaluated the potential of an αvβ3 integrin-targeting radiotracer, (99m)Tc-IDA-D-[c(RGDfK)]2, for SPECT/CT imaging of high-risk plaque in murine atherosclerosis models. In vivo uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 was significantly higher in atherosclerotic aortas than in relatively normal aortas. Comparison with the negative-control peptide, (99m)Tc-IDA-D-[c(RADfK)]2, proved specific binding of (99m)Tc-IDA-D-[c(RGDfK)]2 for plaque lesions in in vivo SPECT/CT and ex vivo autoradiographic imaging. Histopathological characterization revealed that a prominent SPECT signal of (99m)Tc-IDA-D-[c(RGDfK)]2 corresponded to the presence of high-risk plaques with a large necrotic core, a thin fibrous cap, and vibrant neoangiogenic events. Notably, the RGD dimer based (99m)Tc-IDA-D-[c(RGDfK)]2 showed better imaging performance in comparison with the common monomeric RGD peptide probe (123)I-c(RGDyV) and fluorescence tissue assay corroborated this. Our preclinical data demonstrated that (99m)Tc-IDA-D-[c(RGDfK)]2 SPECT/CT is a sensitive tool to noninvasively gauge atherosclerosis beyond vascular anatomy by assessing culprit plaque neovascularization.

  18. Proprotein convertases in human atherosclerotic plaques: the overexpression of FURIN and its substrate cytokines BAFF and APRIL.

    Science.gov (United States)

    Turpeinen, Hannu; Raitoharju, Emma; Oksanen, Anna; Oksala, Niku; Levula, Mari; Lyytikäinen, Leo-Pekka; Järvinen, Otso; Creemers, John W M; Kähönen, Mika; Laaksonen, Reijo; Pelto-Huikko, Markku; Lehtimäki, Terho; Pesu, Marko

    2011-12-01

    Proprotein convertase subtilisin/kexin (PCSK) enzymes cleave proproteins into mature end products. Previously, MBTPS1 and PCSK9 have been shown to regulate cholesterol metabolism and LDL receptor recycling, whereas FURIN and PCSK5 have been suggested to inactivate lipases and regulate inflammation in atherosclerosis. Here, we systematically analyzed the expression of PCSKs and their targets in advanced atherosclerotic plaques. Microarray and quantitative real-time PCR experiments showed that FURIN (42.86 median fold, p = 2.1e-8), but no other PCSK, is universally overexpressed in the plaques of different vascular regions. The mRNA expression screen of PCSK target proteins in plaques identified many known factors, but it also identified the significant upregulation of the previously overlooked furin-processed B cell activating cytokines APRIL (TNFSF13, 2.52 median fold, p = 3.0e-5) and BAFF (TNFSF13B, 2.97 median fold, p = 7.6e-6). The dysregulation of FURIN did not associate with its htSNPs or the previously reported regulatory SNP (-229, rs4932178) in the promoter. Immunohistochemistry experiments showed the upregulation of FURIN in the plaque lymphocytes and macrophages where it was co-expressed with BAFF/TNFSF13B and APRIL/TNFSF13. Our data unequivocally show that FURIN is the primary PCSK that is dysregulated in the immune cells of advanced human atherosclerotic plaques, which implies a role for this enzyme in plaque pathology. Therefore, drugs that inhibit FURIN in arteries may modulate the course of this disease. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban

    Directory of Open Access Journals (Sweden)

    Qianxing Zhou

    2011-01-01

    Full Text Available Aim. Thrombin not only plays a central role in thrombus formation and platelet activation, but also in induction of inflammatory processes. Activated factor X (FXa is traditionally known as an important player in the coagulation cascade responsible for thrombin generation. We assessed the hypothesis that rivaroxaban, a direct FXa inhibitor, attenuates plaque progression and promotes stability of advanced atherosclerotic lesions in an in vivo model. Methods and Results. Rivaroxaban (1 or 5 mg/kg body weight/day or standard chow diet was administered for 26 weeks to apolipoprotein E-deficient mice (n=20 per group with already established atherosclerotic lesions. There was a nonsignificant reduction of lesion progression in the high-concentration group, compared to control mice. FXa inhibition with 5 mg Rivaroxaban/kg/day resulted in increased thickness of the protective fibrous caps (12.3±3.8 μm versus 10.1±2.7 μm; P<.05, as well as in fewer medial erosions and fewer lateral xanthomas, indicating plaque stabilizing properties. Real time-PCR from thoracic aortas revealed that rivaroxaban (5 mg/kg/day treatment reduced mRNA expression of inflammatory mediators, such of IL-6, TNF-α, MCP-1, and Egr-1 (P<.05. Conclusions. Chronic administration of rivaroxaban does not affect lesion progression but downregulates expression of inflammatory mediators and promotes lesion stability in apolipoprotein E-deficient mice.

  20. Coffee consumption and calcified atherosclerotic plaques in the coronary arteries: The NHLBI Family Heart Study.

    Science.gov (United States)

    Patel, Yash R; Gadiraju, Taraka V; Ellison, R Curtis; Hunt, Steven C; Carr, John Jeffrey; Heiss, Gerardo; Arnett, Donna K; Pankow, James S; Gaziano, J Michael; Djoussé, Luc

    2017-02-01

    While a recent meta-analysis of prospective studies reported that coffee consumption is associated with a lower risk of cardiovascular disease mortality, limited and inconsistent data are available on the relation of coffee intake with subclinical disease. Thus, the aim of the present study was to see the association of coffee consumption with the prevalence of atherosclerotic plaque in the coronary arteries in NHLBI Family Heart Study. In a cross-sectional design, we studied 1929 participants of the NHLBI Family Heart Study without known coronary heart disease. Coffee consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac computed tomography. We defined prevalent CAC as an Agatston score of ≥100 and used generalized estimating equations to calculate prevalence ratios of CAC as well as a sensitivity analysis at a range of cutpoints for CAC. Mean age was 56.7 years and 59% of the study subjects were female. In adjusted analysis for age, sex, BMI, smoking, alcohol, physical activity, field center, and energy intake, prevalence ratio (95% CI) for CAC was 1.0 (reference), 0.92 (0.57-1.49), 1.34 (0.86-2.08), 1.30 (0.84-2.02), and 0.99 (0.60-1.64) for coffee consumption of almost never, coffee consumption and prevalent CAC when CAC cut points of 0, 50, 150, 200, and 300 were used. These data do not provide evidence for an association between coffee consumption and prevalent CAC in adult men and women. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  1. Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  2. Assessment of hemodynamic changes near carotid atherosclerotic plaques by using magnetic resonance imaging and computational fluid dynamics

    Directory of Open Access Journals (Sweden)

    Li-na JING

    2014-07-01

    Full Text Available Objective To establish a platform by using carotid MRI and computational fluid dynamics (CFD to assess hemodynamic changes around carotid atherosclerotic plaques.  Methods Thirteen patients with carotid atherosclerosis were recruited in this study. Six volunteers were regarded as normal controls. All the patients and volunteers underwent carotid MRI and contrast-enhanced magnetic resonance angiography (CEMRA. Carotid MRI was used to visualize the plaque structures and components. All plaques were divided into different types according to plaque components. CEMRA images were used to obtain three-dimensional (3D models of carotid bifurcations, whose boundary conditions were specified using CFD front-end software, and then the mesh file of the 3D models were obtained to import to CFD software to visualize hemodynamic maps, including wall shear stress (WSS, static pressure and blood velocity.  Results Fifteen diseased internal carotid arteries (ICAs were assessed. According to the MRI appearance of the plaques, the types of these plaques were from Ⅳ-Ⅴ to Ⅷ. All of these were vulnerable plaques which caused irregular stenosis of ICAs. The WSS, static pressure and blood velocity were (79.86 ± 57.83 Pa, (-7586.81 ± 9313.83 Pa, (2.76±1.81 m/s, respectively in the diseased ICAs group and (2.52 ± 0.58 Pa, (-71.65 ± 30.89 Pa, (0.21 ± 0.06 m/s, respectively in the normal control group. In the diseased ICAs group WSS was elevated heterogenously and static pressure was decreased heterogenously near the plaques. The blood velocity near the plaques was increased but still streamlined. Statistical significant differences were shown for WSS, static pressure and blood velocity between 2 groups (P = 0.000, for all.  Conclusions The platform combining MRI and CFD can be used to analyze the plaque structures and fluid dynamic change near the plaques, suggesting hemodynamics plays an important role in the plaque progression and vulnerability. doi: 10

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Clinical feasibility of 3D automated coronary atherosclerotic plaque quantification algorithm on coronary computed tomography angiography: Comparison with intravascular ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyung-Bok [Yonsei University Health System, Yonsei-Cedar Sinai Integrative Cardiovascular Imaging Research Center, Seoul (Korea, Republic of); Myongji Hospital, Division of Cardiology, Cardiovascular Center, Goyang (Korea, Republic of); Lee, Byoung Kwon [Yonsei University College of Medicine, Division of Cardiology, Gangnam Severance Hospital, Seoul (Korea, Republic of); Shin, Sanghoon [Yonsei University Health System, Yonsei-Cedar Sinai Integrative Cardiovascular Imaging Research Center, Seoul (Korea, Republic of); National Health Insurance Corporation Ilsan Hospital, Division of Cardiology, Goyang (Korea, Republic of); Heo, Ran; Chang, Hyuk-Jae; Chung, Namsik [Yonsei University Health System, Yonsei-Cedar Sinai Integrative Cardiovascular Imaging Research Center, Seoul (Korea, Republic of); Yonsei University Health System, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of); Arsanjani, Reza [Cedars-Sinai Medical Center, Departments of Imaging and Medicine, Cedars-Sinai Heart Institute, Los Angeles, CA (United States); Kitslaar, Pieter H. [Leiden University Medical Center, Department of Radiology, Division of Image Processing, Leiden (Netherlands); Medis medical Imaging Systems B.V., Leiden (Netherlands); Broersen, Alexander; Dijkstra, Jouke [Leiden University Medical Center, Department of Radiology, Division of Image Processing, Leiden (Netherlands); Ahn, Sung Gyun [Yonsei University Wonju Severance Christian Hospital, Division of Cardiology, Wonju (Korea, Republic of); Min, James K. [New York-Presbyterian Hospital, Institute for Cardiovascular Imaging, Weill-Cornell Medical College, New York, NY (United States); Hong, Myeong-Ki; Jang, Yangsoo [Yonsei University Health System, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of)

    2015-10-15

    To evaluate the diagnostic performance of automated coronary atherosclerotic plaque quantification (QCT) by different users (expert/non-expert/automatic). One hundred fifty coronary artery segments from 142 patients who underwent coronary computed tomography angiography (CCTA) and intravascular ultrasound (IVUS) were analyzed. Minimal lumen area (MLA), maximal lumen area stenosis percentage (%AS), mean plaque burden percentage (%PB), and plaque volume were measured semi-automatically by expert, non-expert, and fully automatic QCT analyses, and then compared to IVUS. Between IVUS and expert QCT analysis, the correlation coefficients (r) for the MLA, %AS, %PB, and plaque volume were excellent: 0.89 (p < 0.001), 0.84 (p < 0.001), 0.91 (p < 0.001), and 0.94 (p < 0.001), respectively. There were no significant differences in the mean parameters (all p values >0.05) except %AS (p = 0.01). The automatic QCT analysis showed comparable performance to non-expert QCT analysis, showing correlation coefficients (r) of the MLA (0.80 vs. 0.82), %AS (0.82 vs. 0.80), %PB (0.84 vs. 0.73), and plaque volume (0.84 vs. 0.79) when they were compared to IVUS, respectively. Fully automatic QCT analysis showed clinical utility compared with IVUS, as well as a compelling performance when compared with semiautomatic analyses. (orig.)

  5. Evaluation of 68Ga-Glutamate Carboxypeptidase II Ligand Positron Emission Tomography for Clinical Molecular Imaging of Atherosclerotic Plaque Neovascularization.

    Science.gov (United States)

    Derlin, Thorsten; Thiele, Johannes; Weiberg, Desiree; Thackeray, James T; Püschel, Klaus; Wester, Hans-Jürgen; Aguirre Dávila, Lukas; Larena-Avellaneda, Axel; Daum, Günter; Bengel, Frank M; Schumacher, Udo

    2016-11-01

    Intraplaque neovascularization contributes to the progression and rupture of atherosclerotic lesions. Glutamate carboxypeptidase II (GCPII) is strongly expressed by endothelial cells of tumor neovasculature and plays a major role in hypoxia-induced neovascularization in rodent models of benign diseases. We hypothesized that GCPII expression may play a role in intraplaque neovascularization and may represent a target for imaging of atherosclerotic lesions. The aim of this study was to determine frequency, pattern, and clinical correlates of vessel wall uptake of a (68)Ga-GCPII ligand for positron emission tomographic imaging. Data from 150 patients undergoing (68)Ga-GCPII ligand positron emission tomography were evaluated. Tracer uptake in various arterial segments was analyzed and was compared with calcified plaque burden, cardiovascular risk factors, and immunohistochemistry of carotid specimens. Focal arterial uptake of (68)Ga-GCPII ligand was identified at 5776 sites in 99.3% of patients. The prevalence of uptake sites was highest in the thoracic aorta; 18.4% of lesions with tracer uptake were colocalized with calcified plaque. High injected dose (P=0.0005) and obesity (P=0.007) were significantly associated with (68)Ga-GCPII ligand accumulation, but other cardiovascular risk factors showed no association. The number of (68)Ga-GCPII ligand uptake sites was significantly associated with overweight condition (P=0.0154). Immunohistochemistry did not show GCPII expression. Autoradiographic blocking studies indicated nonspecific tracer binding. (68)Ga-GCPII ligand positron emission tomography does not identify vascular lesions associated with atherosclerotic risk. Foci of tracer accumulation are likely caused by nonspecific tracer binding and are in part noise-related. Taken together, GCPII may not be a priority target for imaging of atherosclerotic lesions. © 2016 American Heart Association, Inc.

  6. How radiation influences atherosclerotic plaque development: a biophysical approach in ApoE⁻/⁻ mice.

    Science.gov (United States)

    Kloosterman, Astrid; Dillen, Teun van; Bijwaard, Harmen; Heeneman, Sylvia; Hoving, Saske; Stewart, Fiona A; Dekkers, Fieke

    2017-11-01

    Atherosclerosis is the development of lipid-laden plaques in arteries and is nowadays considered as an inflammatory disease. It has been shown that high doses of ionizing radiation, as used in radiotherapy, can increase the risk of development or progression of atherosclerosis. To elucidate the effects of radiation on atherosclerosis, we propose a mathematical model to describe radiation-promoted plaque development. This model distinguishes itself from other models by combining plaque initiation and plaque growth, and by incorporating information from biological experiments. It is based on two consecutive processes: a probabilistic dose-dependent plaque initiation process, followed by deterministic plaque growth. As a proof of principle, experimental plaque size data from carotid arteries from irradiated ApoE[Formula: see text] mice was used to illustrate how this model can provide insight into the underlying biological processes. This analysis supports the promoting role for radiation in plaque initiation, but the model can easily be extended to include dose-related effects on plaque growth if available experimental data would point in that direction. Moreover, the model could assist in designing future biological experiments on this research topic. Additional biological data such as plaque size data from chronically-irradiated mice or experimental data sets with a larger variety in biological parameters can help to further unravel the influence of radiation on plaque development. To the authors' knowledge, this is the first biophysical model that combines probabilistic and mechanistic modeling which uses experimental data to investigate the influence of radiation on plaque development.

  7. How radiation influences atherosclerotic plaque development. A biophysical approach in ApoE{sup -/-} mice

    Energy Technology Data Exchange (ETDEWEB)

    Kloosterman, Astrid; Dillen, Teun van; Dekkers, Fieke [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Safety and Security, Bilthoven (Netherlands); Bijwaard, Harmen [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Safety and Security, Bilthoven (Netherlands); Inholland University of Applied Sciences, Medical Technology Research Group, Haarlem (Netherlands); Heeneman, Sylvia [Maastricht University Medical Center, Experimental Vascular Pathology group, Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); Hoving, Saske; Stewart, Fiona A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Biological Stress Response (H3), Amsterdam (Netherlands)

    2017-11-15

    Atherosclerosis is the development of lipid-laden plaques in arteries and is nowadays considered as an inflammatory disease. It has been shown that high doses of ionizing radiation, as used in radiotherapy, can increase the risk of development or progression of atherosclerosis. To elucidate the effects of radiation on atherosclerosis, we propose a mathematical model to describe radiation-promoted plaque development. This model distinguishes itself from other models by combining plaque initiation and plaque growth, and by incorporating information from biological experiments. It is based on two consecutive processes: a probabilistic dose-dependent plaque initiation process, followed by deterministic plaque growth. As a proof of principle, experimental plaque size data from carotid arteries from irradiated ApoE{sup -/-} mice was used to illustrate how this model can provide insight into the underlying biological processes. This analysis supports the promoting role for radiation in plaque initiation, but the model can easily be extended to include dose-related effects on plaque growth if available experimental data would point in that direction. Moreover, the model could assist in designing future biological experiments on this research topic. Additional biological data such as plaque size data from chronically-irradiated mice or experimental data sets with a larger variety in biological parameters can help to further unravel the influence of radiation on plaque development. To the authors' knowledge, this is the first biophysical model that combines probabilistic and mechanistic modeling which uses experimental data to investigate the influence of radiation on plaque development. (orig.)

  8. 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

    to plaque vulnerability. Ficolins and MBL were found both in plaques' necrotic core and tunica media. Patients with vulnerable plaques showed decreased plasma levels and intraplaque deposition of ficolin-2. Symptomatic patients experiencing a transient ischemic attack had lower plasma levels of ficolin-1...

  9. Characteristics of carotid atherosclerotic plaques of chronic lipid apheresis patients as assessed by In Vivo High-Resolution CMR - a comparative analysis

    Directory of Open Access Journals (Sweden)

    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.

  10. Ticagrelor promotes atherosclerotic plaque stability in a mouse model of advanced atherosclerosis.

    Science.gov (United States)

    Preusch, Michael R; Rusnak, Jonas; Staudacher, Kathrin; Mogler, Carolin; Uhlmann, Lorenz; Sievers, Philipp; Bea, Florian; Katus, Hugo A; Blessing, Erwin; Staudacher, Ingo

    2016-01-01

    There is increasing evidence supporting the role of platelets in atherosclerotic vascular disease. The G-protein-coupled receptor P2Y12 is a central mediator of platelet activation and aggregation but has also been linked to platelet-independent vascular disease. Ticagrelor is an oral P2Y12 antagonist that is used as a standard treatment in patients after acute myocardial infarction. However, the effects of ticagrelor on advanced atherosclerosis have not been investigated. Twenty-week-old apolipoprotein-E-deficient mice received standard chow or standard chow supplemented with 0.15% ticagrelor (approximately 270 mg/kg/day) for 25 weeks. The lesion area was evaluated in the aortic sinus by Movat's pentachrome staining and lesion composition, thickness of the fibrous cap, and size of the necrotic core evaluated by morphometry. RAW 264.7 macrophages were serum starved and treated with ticagrelor in vitro for the detection and quantification of apoptosis. In addition, oxLDL uptake in RAW 264.7 macrophages was evaluated. A trend toward the reduction of total lesion size was detected. However, data did not reach the levels of significance (control, n=11, 565,881 μm(2) [interquartile range {IQR} 454,778-603,925 μm(2)] versus ticagrelor, n=13, 462,595 μm(2) [IQR 379,740-546,037 μm(2)]; P=0.1). A significant reduction in the relative area of the necrotic core (control, n=11, 0.46 [IQR 0.4-0.51] versus ticagrelor, n=13, 0.34 [IQR 0.31-0.39]; P=0.008), and a significant increase in fibrous caps thickness (control, n=11, 3.7 μm [IQR 3.4-4.2 μm] versus ticagrelor, n=13, 4.7 [IQR 4.3-5.5 μm], P=0.04) were seen in ticagrelor-treated mice. In vitro studies demonstrated a reduction in apoptotic RAW 264.7 macrophages (control 0.07±0.03 versus ticagrelor 0.03±0.03; P=0.0002) when incubated with ticagrelor. Uptake of oxLDL in RAW 264.7 was significantly reduced when treated with ticagrelor (control 9.2 [IQR 5.3-12.9] versus ticagrelor 6.4 [IQR 2.5-9.5], P=0.02). The present

  11. Community-based statins and advanced carotid plaque: Role of CD163 positive macrophages in lipoprotein-associated phospholipase A2 activity in atherosclerotic plaque.

    Science.gov (United States)

    Otsuka, Fumiyuki; Zhao, XiaoQing; Trout, Hugh H; Qiao, Ye; Wasserman, Bruce A; Nakano, Masataka; Macphee, Colin H; Brandt, Martin; Krug-Gourley, Sue; Guo, Liang; Ladich, Elena R; Cheng, Qi; Davis, Harry R; Finn, Aloke V; Virmani, Renu; Kolodgie, Frank D

    2017-12-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzymatic inflammatory biomarker primarily bound to low-density lipoprotein cholesterol, is associated with an approximate twofold increased risk of cardiovascular disease and stroke. Despite indications that circulating Lp-PLA2 is sensitive to statins, it remains largely unknown whether statin usage exerts local effects on Lp-PLA2 expression at the site of atheromatous plaque. Carotid plaques (n = 38) were prospectively collected from symptomatic (n = 18) and asymptomatic (n = 20) patients with (n = 20) or without (n = 18) documented statin history. In all cases, endarterectomy was performed where the primary stenosis was removed in an undisturbed manner. Serial cryosections of the presenting lesion were assessed histologically for macrophages, Lp-PLA2, and cell death (apoptotic index). Symptomatic lesions exhibited less calcification, with greater inflammation characterized by increased expression of CD68+ and CD163+ macrophage subsets, and Lp-PLA2. Symptomatic plaques also exhibited greater necrotic core area and increased apoptosis, as compared with asymptomatic lesions. In contrast, statin treatment did not appear to influence any of these parameters, except for the extent of apoptosis, which was less in statin treated as compared with statin naïve lesions. Overall, Lp-PLA2 expression correlated positively with necrotic core area, CD68+ and CD163+ macrophage area, and cell death. Finally, in vitro assays and dual immunofluorescence staining confirmed CD163-expressing monocytes/macrophages are also a major source of Lp-PLA2. Statin treatment has no effect on local atherosclerotic lesion Lp-PLA2 activity, therefore, the addition of anti-inflammatory treatments to further decrease macrophage Lp-PLA2 expression in atherosclerotic lesions may reduce lesional inflammation and cell death, and prevent necrotic core expansion and lesion progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Data on the lipoprotein (a, coronary atherosclerotic burden and vulnerable plaque phenotype in angiographic obstructive coronary artery disease

    Directory of Open Access Journals (Sweden)

    Giampaolo Niccoli

    2016-06-01

    Full Text Available Lipoprotein Lp(a represents an independent risk factor for coronary artery disease (CAD. However, its association with CAD burden and lipid rich plaques prone to rupture in patients with acute coronary syndrome (ACS still remains unknown. These data aim to investigate the association among serum Lipoprotein(a (Lpa levels, coronary atherosclerotic burden and features of culprit plaque in patients with ACS and obstructive CAD. For his reason, a total of 500 ACS patients were enrolled for the angiographic cohort and 51 ACS patients were enrolled for the optical coherence tomography (OCT cohort. Angiographic CAD severity was assessed by Sullivan score and by Bogaty score including stenosis score and extent index, whereas OCT plaque features were evaluated at the site of the minimal lumen area and along the culprit segment. In the angiographic cohort, Lp(a was a weak independent predictor of Sullivan score (p30 md/dl compared to patients with lower Lp(a levels (<30 md/dl exhibited a higher prevalence of lipidic plaque at the site of the culprit stenosis (P=0.02, a wider lipid arc (p=0.003 and a higher prevalence of thin-cap fibroatheroma (p=0.004

  13. Coronary computed tomography angiography based assessment of endothelial shear stress and its association with atherosclerotic plaque distribution in-vivo.

    Directory of Open Access Journals (Sweden)

    Holger Hetterich

    Full Text Available PURPOSE: The relationship between low endothelial shear stress (ESS and coronary atherosclerosis is well established. ESS assessment so far depended on invasive procedures. The aim of this study was to demonstrate the relationship between ESS and coronary atherosclerosis by using non-invasive coronary computed tomography angiography (CTA for computational fluid dynamics (CFD simulations. METHODS: A total number of 7 consecutive patients with suspected coronary artery disease who received CTA and invasive angiography with IVUS analysis were included in this study. CTA examinations were performed using a dual-source scanner. These datasets were used to build a 3D mesh model. CFD calculations were performed using a validated CFD solver. The presence of plaque was assumed if the thickness of the intima-media complex exceeded 0.3 mm in IVUS. Plaque composition was derived by IVUS radiofrequency data analysis. RESULTS: Plaque was present in 32.1% of all analyzed cross-sections. Plaque prevalence was highest in areas of low ESS (49.6% and high ESS (34.8%. In parts exposed to intermediate-low and intermediate-high ESS few plaques were found (20.0% and 24.0% (p<0.001. Wall thickness was closely associated with local ESS. Intima-media thickness was 0.43±0.34 mm in low and 0.38±0.32 mm in high ESS segments. It was significantly lower when the arterial wall was exposed to intermediate ESS (0.25±0.18 mm and 0.28 ± 0.20 mm (p<0.001. Fibrofatty tissue was predominately found in areas exposed to low ESS (p≤0.023. CONCLUSIONS: In this study a close association of atherosclerotic plaque distribution and ESS pattern could be demonstrated in-vivo. Adding CFD analysis to coronary CTA offers the possibility to gather morphologic and physiologic data within one non-invasive examination.

  14. Association between albuminuria, atherosclerotic plaques, elevated pulse wave velocity, age, risk category and prognosis in apparently healthy individuals

    DEFF Research Database (Denmark)

    Greve, Sara V; Blicher, Marie K; Blyme, Adam

    2014-01-01

    atherosclerotic plaques or albuminuria defined as urine albumin/creatinine ratio at least 90th percentile of 0.73/1.06 mg/mmol men/women. In 2006, the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for ischemic heart disease was recorded (n...... = 229). RESULTS: With increasing age, SCORE or FRS risk group, prevalence of cfPWV at least 12 m/s (5.2, 14.5, 35.3, 53.5% or 4.4, 15.6, 50.9, 66.1% or 4.0, 9.5, 32.1, 56.1%), atherosclerotic plaque (4.0, 19.0, 35.3, 53.5% or 3.5, 16.8, 43.7, 55.9%, or 6.6, 7.6, 9.8, 20.0%) and albuminuria (7.9, 8.7, 11.......4, 20.6% or 7.9, 8.2, 16.6, 19.5% or 6.6, 7.6, 9.8, 20.0%) increased, all P albuminuria in individuals aged 61 or 71 years, with moderate or very high SCORE or intermediate or high FRS (all P 

  15. Profilin-1 is expressed in human atherosclerotic plaques and induces atherogenic effects on vascular smooth muscle cells.

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    Evren Caglayan

    2010-10-01

    Full Text Available Profilin-1 is an ubiquitous actin binding protein. Under pathological conditions such as diabetes, profilin-1 levels are increased in the vascular endothelium. We recently demonstrated that profilin-1 overexpression triggers indicators of endothelial dysfunction downstream of LDL signaling, and that attenuated expression of profilin-1 confers protection from atherosclerosis in vivo.Here we monitored profilin-1 expression in human atherosclerotic plaques by immunofluorescent staining. The effects of recombinant profilin-1 on atherogenic signaling pathways and cellular responses such as DNA synthesis (BrdU-incorporation and chemotaxis (modified Boyden-chamber were evaluated in cultured rat aortic and human coronary vascular smooth muscle cells (VSMCs. Furthermore, the correlation between profilin-1 serum levels and the degree of atherosclerosis was assessed in humans.In coronary arteries from patients with coronary heart disease, we found markedly enhanced profilin expression in atherosclerotic plaques compared to the normal vessel wall. Stimulation of rat aortic and human coronary VSMCs with recombinant profilin-1 (10(-6 M in vitro led to activation of intracellular signaling cascades such as phosphorylation of Erk1/2, p70(S6 kinase and PI3K/Akt within 10 minutes. Furthermore, profilin-1 concentration-dependently induced DNA-synthesis and migration of both rat and human VSMCs, respectively. Inhibition of PI3K (Wortmannin, LY294002 or Src-family kinases (SU6656, PP2, but not PLCγ (U73122, completely abolished profilin-induced cell cycle progression, whereas PI3K inhibition partially reduced the chemotactic response. Finally, we found that profilin-1 serum levels were significantly elevated in patients with severe atherosclerosis in humans (p<0.001 vs. no atherosclerosis or control group.Profilin-1 expression is significantly enhanced in human atherosclerotic plaques compared to the normal vessel wall, and the serum levels of profilin-1 correlate

  16. Ticagrelor promotes atherosclerotic plaque stability in a mouse model of advanced atherosclerosis

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    Preusch MR

    2016-08-01

    Full Text Available Michael R Preusch,1 Jonas Rusnak,1 Kathrin Staudacher,2 Carolin Mogler,3 Lorenz Uhlmann,4 Philipp Sievers,1 Florian Bea,1 Hugo A Katus,1 Erwin Blessing,1 Ingo Staudacher1 1Department of Internal Medicine III, 2Department of Neonatology, 3Department of Pathology, 4Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Objective: There is increasing evidence supporting the role of platelets in atherosclerotic vascular disease. The G-protein-coupled receptor P2Y12 is a central mediator of platelet activation and aggregation but has also been linked to platelet-independent vascular disease. Ticagrelor is an oral P2Y12 antagonist that is used as a standard treatment in patients after acute myocardial infarction. However, the effects of ticagrelor on advanced atherosclerosis have not been investigated.Materials and methods: Twenty-week-old apolipoprotein-E-deficient mice received standard chow or standard chow supplemented with 0.15% ticagrelor (approximately 270 mg/kg/day for 25 weeks. The lesion area was evaluated in the aortic sinus by Movat’s pentachrome staining and lesion composition, thickness of the fibrous cap, and size of the necrotic core evaluated by morphometry. RAW 264.7 macrophages were serum starved and treated with ticagrelor in vitro for the detection and quantification of apoptosis. In addition, oxLDL uptake in RAW 264.7 macrophages was evaluated.Results: A trend toward the reduction of total lesion size was detected. However, data did not reach the levels of significance (control, n=11, 565,881 µm2 [interquartile range {IQR} 454,778–603,925 µm2] versus ticagrelor, n=13, 462,595 µm2 [IQR 379,740–546,037 µm2]; P=0.1. A significant reduction in the relative area of the necrotic core (control, n=11, 0.46 [IQR 0.4–0.51] versus ticagrelor, n=13, 0.34 [IQR 0.31–0.39]; P=0.008, and a significant increase in fibrous caps thickness (control, n=11, 3.7 µm [IQR 3.4–4.2 µm] versus

  17. ACAT inhibition reduces the progression of preexisting, advanced atherosclerotic mouse lesions without plaque or systemic toxicity.

    Science.gov (United States)

    Rong, James X; Blachford, Courtney; Feig, Jonathan E; Bander, Ilda; Mayne, Jeffrey; Kusunoki, Jun; Miller, Christine; Davis, Matthew; Wilson, Martha; Dehn, Shirley; Thorp, Edward; Tabas, Ira; Taubman, Mark B; Rudel, Lawrence L; Fisher, Edward A

    2013-01-01

    Acyl-CoA:cholesterol acyltransferase (ACAT) converts cholesterol to cholesteryl esters in plaque foam cells. Complete deficiency of macrophage ACAT has been shown to increase atherosclerosis in hypercholesterolemic mice because of cytotoxicity from free cholesterol accumulation, whereas we previously showed that partial ACAT inhibition by Fujirebio compound F1394 decreased early atherosclerosis development. In this report, we tested F1394 effects on preestablished, advanced lesions of apolipoprotein-E-deficient mice. Apolipoprotein-E-deficient mice on Western diet for 14 weeks developed advanced plaques, and were either euthanized (Baseline), or continued on Western diet with or without F1394 and euthanized after 14 more weeks. F1394 was not associated with systemic toxicity. Compared with the baseline group, lesion size progressed in both groups; however, F1394 significantly retarded plaque progression and reduced plaque macrophage, free and esterified cholesterol, and tissue factor contents compared with the untreated group. Apoptosis of plaque cells was not increased, consistent with the decrease in lesional free cholesterol. There was no increase in plaque necrosis and unimpaired efferocytosis (phagocytic clearance of apoptotic cells). The effects of F1394 were independent of changes in plasma cholesterol levels. Partial ACAT inhibition by F1394 lowered plaque cholesterol content and had other antiatherogenic effects in advanced lesions in apolipoprotein-E-deficient mice without overt systemic or plaque toxicity, suggesting the continued potential of ACAT inhibition for the clinical treatment of atherosclerosis, in spite of recent trial data.

  18. Determinants of carotid atherosclerotic plaque burden in a stroke-free population

    NARCIS (Netherlands)

    Selwaness, Mariana; Hameeteman, Reinhard; Van 't Klooster, Ronald; Van den Bouwhuijsen, Quirijn; Hofman, Albert; Franco, Oscar H.; Niessen, W.J.; Klein, Stefan; Vernooij, Meike W.; Van Der Lugt, Aad; Wentzel, Jolanda J.

    2016-01-01

    Background and aims In a large stroke-free population, we sought to identify cardiovascular risk factors and carotid plaque components associated with carotid plaque burden, lumen volume and stenosis. Methods The carotid arteries of 1562 stroke-free participants from The Rotterdam Study were

  19. Fibrillar amyloid plaque formation precedes microglial activation.

    Science.gov (United States)

    Jung, Christian K E; Keppler, Kevin; Steinbach, Sonja; Blazquez-Llorca, Lidia; Herms, Jochen

    2015-01-01

    In Alzheimer's disease (AD), hallmark β-amyloid deposits are characterized by the presence of activated microglia around them. Despite an extensive characterization of the relation of amyloid plaques with microglia, little is known about the initiation of this interaction. In this study, the detailed investigation of very small plaques in brain slices in AD transgenic mice of the line APP-PS1(dE9) revealed different levels of microglia recruitment. Analysing plaques with a diameter of up to 10 μm we find that only the half are associated with clear morphologically activated microglia. Utilizing in vivo imaging of new appearing amyloid plaques in double-transgenic APP-PS1(dE9)xCX3CR1+/- mice further characterized the dynamic of morphological microglia activation. We observed no correlation of morphological microglia activation and plaque volume or plaque lifetime. Taken together, our results demonstrate a very prominent variation in size as well as in lifetime of new plaques relative to the state of microglia reaction. These observations might question the existing view that amyloid deposits by themselves are sufficient to attract and activate microglia in vivo.

  20. Differential effects of PARP inhibition on vascular cell survival and ACAT-1 expression favouring atherosclerotic plaque stability.

    Science.gov (United States)

    Hans, Chetan P; Zerfaoui, Mourad; Naura, Amarjit S; Catling, Andrew; Boulares, A Hamid

    2008-06-01

    The aim of this study was to take a combination of animal and cell culture approaches to examine the individual responses of vascular cells to varying inflammatory factors in order to gain insights on the mechanism(s) by which poly(ADP-ribose) polymerase (PARP) inhibition promotes factors of plaque stability. Apolipoprotein (ApoE(-/-)) mice fed a high-fat diet were used as a model of atherosclerosis. Primary endothelial cells, smooth muscle cells (SMCs), and ex-vivo generated foam cells (FCs) were used in our in vitro studies. PARP inhibition significantly decreased the markers of oxidative stress and caspase-3 activation and increased smooth muscle actin within plaques from ApoE(-/-) mice fed a high-fat diet. PARP inhibition protected against apoptosis and/or necrosis in SMCs and endothelial cells in response to H(2)O(2) or tumour necrosis factor (TNF). Remarkably, PARP inhibition in FCs resulted in significant sensitization to 7-ketocholesterol (7-KC) by increasing cellular-toxic-free cholesterol, potentially through a down-regulation of acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) expression. 7-KC induced necrosis exclusively in endothelial cells, which was, surprisingly, unaffected by PARP inhibition indicating that PARP inhibition does not prevent all forms of necrotic cell death. In SMCs, PARP-1 inhibition by gene deletion conferred protection against 7-KC or TNF, potentially by reducing caspase-3-like activation, preventing induction of c-Jun N-terminal protein kinase phosphorylation, and inducing extracellular signal-regulated kinase phosphorylation independently of PARP classical enzymatic activity. These data present PARP-1 as an important player in the death of cells constituting atherosclerotic plaques contributing to plaque dynamics. PARP inhibition may be a protective, a neutral, or a sensitizing factor. Additionally, PARP-1 may be a novel factor that can alter lipid metabolism. These novel functions of PARP not only challenge the current

  1. Acoustic radiation force beam sequence performance for detection and material characterization of atherosclerotic plaques: preclinical, ex vivo results.

    Science.gov (United States)

    Behler, Russell H; Czernuszewicz, Tomasz J; Wu, Chih-Da; Nichols, Timothy C; Zhu, Hongtu; Homeister, Jonathon W; Merricks, Elizabeth P; Gallippi, Caterina M

    2013-12-01

    This work presents preclinical data demonstrating performance of acoustic radiation force (ARF)-based elasticity imaging with five different beam sequences for atherosclerotic plaque detection and material characterization. Twelve trained, blinded readers evaluated parametric images taken ex vivo under simulated in vivo conditions of 22 porcine femoral arterial segments. Receiver operating characteristic (ROC) curve analysis was carried out to quantify reader performance using spatially-matched immunohistochemistry for validation. The beam sequences employed had high sensitivity (sens) and specificity (spec) for detecting Type III+ plaques (sens: 85%, spec: 79%), lipid pools (sens: 80%, spec: 86%), fibrous caps (sens: 86%, spec: 82%), calcium (sens: 96%, spec: 85%), collagen (sens: 78%, spec: 77%), and disrupted internal elastic lamina (sens: 92%, spec: 75%). 1:1 single-receive tracking yielded the highest median areas under the ROC curve (AUC), but was not statistically significantly higher than 4:1 parallel-receive tracking. Excitation focal configuration did not result in statistically different AUCs. Overall, these results suggest ARF-based imaging is relevant to detecting and characterizing plaques and support its use for diagnosing and monitoring atherosclerosis.

  2. The Clinical Value of High-Intensity Signals on the Coronary Atherosclerotic Plaques: Noncontrast T1-Weighted Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Shoichi Ehara

    2016-07-01

    Full Text Available Over the past several decades, significant progress has been made in the pathohistological assessment of vulnerable plaques and in invasive intravascular imaging techniques. However, the assessment of plaque morphology by invasive modalities is of limited value for the detection of subclinical coronary atherosclerosis and the subsequent prediction or prevention of acute cardiovascular events. Recently, magnetic resonance (MR imaging technology has reached a sufficient level of spatial resolution, which allowed the plaque visualization of large and static arteries such as the carotids and aorta. However, coronary wall imaging by MR is still challenging due to the small size of coronary arteries, cardiac and respiratory motion, and the low contrast-to-noise ratio between the coronary artery wall and the surrounding structures. Following the introduction of carotid plaque imaging with noncontrast T1-weighted imaging (T1WI, some investigators have reported that coronary artery high-intensity signals on T1WI are associated with vulnerable plaque morphology and an increased risk of future cardiac events. Although there are several limitations and issues that need to be resolved, this novel MR technique for coronary plaque imaging could influence treatment strategies for atherothrombotic disease and may be useful for understanding the pathophysiological mechanisms of atherothrombotic plaque formation.

  3. Variations in Echogenicity in Carotid and Femoral Atherosclerotic Plaques with Pycnogenol + Centella Asiatica Supplementation.

    Science.gov (United States)

    Belcaro, Gianni; Cornelli, Umberto

    2017-06-01

    This registry study evaluated echogenicity of carotid-femoral plaques in asymptomatic subjects with increased oxidative stress and risk factors (mild hypertension, hypercholesterolemia). Supplementation with the combination Pycnogenol-CA (centella asiatica) on the echogenicity of plaques was assessed at 6 months (79 subjects). A standard management (SM) plan was used in all subjects (control of risk factors, lifestyle changes); 36 subjects used the supplements +SM; 43 SM only. The groups were comparable. High-resolution ultrasound evaluated echogenicity and plaque structure. Pycnogenol (150 mg/day) and CA (Centellicum, 450 mg/day) were used. At 6 months, cholesterol was reduced (p Pycnogenol-CA appears to improve echogenicity and stability of complex plaques in 6 months.

  4. Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability

    DEFF Research Database (Denmark)

    Olson, Fredrik J; Thurison, Tine; Ryndel, Mikael

    2009-01-01

    OBJECTIVES:: To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability. DESIGN AND METHODS:: Plasma concentrations of suPAR(I-III), suPAR(II-III) and uPAR(I) were measured by time-resolved fluorescence...... immunoassays in Caucasian patients operated for symptomatic carotid atherosclerosis (n=255). Local suPAR release from plaques into the circulation was assessed in plasma passing retrogradely over the plaque in the carotid artery, collected during surgery (n=7). RESULTS:: The suPAR(I-III) (P=0.03) and su......PAR(II-III) (P=0.006) concentrations were higher after ischemic strokes and transient ischemic attacks, i.e., clinical subgroups associated with poorer prognosis and a less stable plaque phenotype, than after amaurosis fugax. Slightly elevated suPAR(I-III) levels were found in plasma from the carotid lesion...

  5. Folate receptor-β imaging using 99mTc-folate to explore distribution of polarized macrophage populations in human atherosclerotic plaque

    NARCIS (Netherlands)

    Jager, Nynke A.; Westra, Johanna; Golestani, Reza; van Dam, Gooitzen M.; Low, Philip S.; Tio, Rene A.; Slart, Riemer H. J. A.; Boersma, Hendrikus; Bijl, Marc; Zeebregts, Clark J.

    2014-01-01

    UNLABELLED: In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the

  6. Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque

    DEFF Research Database (Denmark)

    Fu, S; Davies, Michael Jonathan; Stocker, R

    1998-01-01

    Oxidative damage might be important in atherogenesis. Oxidized lipids are present at significant concentrations in advanced human plaque, although tissue antioxidants are mostly present at normal concentrations. Indirect evidence of protein modification (notably derivatization of lysine) or oxida......Oxidative damage might be important in atherogenesis. Oxidized lipids are present at significant concentrations in advanced human plaque, although tissue antioxidants are mostly present at normal concentrations. Indirect evidence of protein modification (notably derivatization of lysine...

  7. Effect of bezafibrate therapy on atherosclerotic aortic plaques detected by MRI in dyslipidemic patients with hypertriglyceridemia.

    Science.gov (United States)

    Ayaori, Makoto; Momiyama, Yukihiko; Fayad, Zahi A; Yonemura, Atsushi; Ohmori, Reiko; Kihara, Teruyoshi; Tanaka, Nobukiyo; Nakaya, Kazuhiro; Ogura, Masatsune; Sawada, Shojiro; Taniguchi, Hiroaki; Kusuhara, Masatoshi; Nagata, Masayoshi; Nakamura, Haruo; Ohsuzu, Fumitaka

    2008-01-01

    Fibrates reduce triglycerides (TG) and increase HDL-cholesterol levels, but there was no report showing plaque regression by fibrates. Using MRI, we investigated the effects of bezafibrate on aortic plaques in 22 dyslipidemic patients. All patients were asked to receive 400mg bezafibrate, but 8 who declined to have bezafibrate became the control group. Changes in vessel wall area (VWA) and lumen area (LA) from baseline to 1-year were evaluated. Bezafibrate reduced TG (-55%) and increased HDL-cholesterol levels (+29%). Bezafibrate reduced HDL size and increased LDL size. In thoracic plaques, bezafibrate reduced VWA (-6%, Preduction and HDL-cholesterol increase. Notably, VWA change in only abdominal plaques correlated with HDL size reduction and LDL size increase. Thus, bezafibrate induced plaque regression in thoracic and abdominal aortas with marked TG reduction and HDL-cholesterol increase, but the processes of plaque regression and vascular remodeling may differ between thoracic and abdominal aortas. However, because our study was not a controlled, randomized trial, further study is needed.

  8. Atherosclerotic Plaque Stability Is Affected by the Chemokine CXCL10 in Both Mice and Humans

    Directory of Open Access Journals (Sweden)

    Dolf Segers

    2011-01-01

    Full Text Available Background. The chemokine CXCL10 is specifically upregulated during experimental development of plaque with an unstable phenotype. In this study we evaluated the functional consequences of these findings in mice and humans. Methods and Results. In ApoE-/- mice, we induced unstable plaque with using a flow-altering device around the carotid artery. From week 1 to 4, mice were injected with a neutralizing CXCL10 antibody. After 9 weeks, CXCL10 inhibition resulted in a more stable plaque phenotype: collagen increased by 58% (P=0.002, smooth muscle cell content increased 2-fold (P=0.03, while macrophage MHC class II expression decreased by 50% (P=0.005. Also, the size of necrotic cores decreased by 41% (P=0.01. In 106 human carotid endarterectomy specimens we found that increasing concentrations of CXCL10 strongly associate with an increase in atheromatous plaque phenotype (ANOVA, P=0.003, with high macrophage, low smooth muscle cell, and low collagen content. Conclusions. In the present study we showed that CXCL10 is associated with the development of vulnerable plaque in human and mice. We conclude that CXCL10 might provide a new lead towards plaque-stabilizing therapy.

  9. Coronary artery plaque formation at coronary CT angiography: morphological analysis and relationship to hemodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Enrico, Benedetta [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Universita' Cattolica del Sacro Cuore, Department of Radiology, Rome (Italy); Suranyi, Pal; Costello, Philip [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Thilo, Christian; Schoepf, U.J. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Division of Cardiology, Department of Medicine, Charleston, SC (United States); Bonomo, Lorenzo [Universita' Cattolica del Sacro Cuore, Department of Radiology, Rome (Italy)

    2009-04-15

    We aimed to demonstrate that coronary CT angiography (cCTA) can be used to non-invasively study the effect of hemodynamic factors in the pathophysiology of plaque formation. cCTA data of 73 patients were analyzed. All detected plaques were classified according to location (bifurcation, non-branching segment), configuration (eccentric, concentric), orientation (myocardial, lateral, epicardial side of the vessel wall), and composition (calcified, mixed, non-calcified). Bifurcation lesions were further characterized using the Medina classification. Of 382 plaques, 8.1% were in the LM, 46.3% in the LAD, 18.3% in the LCx, and 25.9% in the RCA. Also, 25.1% were completely calcified, 72.3% were mixed, and 2.6% were purely non-calcified. Of the plaques, 51.3% were bifurcation lesions. The most frequent (40%) Medina pattern was 1.1.0 (lesion starts before, extends beyond bifurcation, sparing the side branch). Eighty percent of plaques were eccentric. A significant (p < 0.01) majority (55%) were on the myocardial side, while 17.3% were lateral, and 27.7% epicardial. Of all non-calcified and mixed plaques, 45.1% (p < 0.01) were myocardial, whereas only 14.3% were lateral, 20.6% epicardial, and 19.9% concentric. We conclude that cCTA can non-invasively study the effect of vascular hemodynamics, such as turbulent flow (bifurcations) and low shear stress (myocardial vessel wall), on the distribution and composition of atherosclerotic plaque deposition. (orig.)

  10. 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

  11. Clinical Molecular Imaging of Chemokine Receptor CXCR4 Expression in Atherosclerotic Plaque using (68)Ga-Pentixafor PET: Correlation with Cardiovascular Risk Factors and Calcified Plaque Burden.

    Science.gov (United States)

    Weiberg, Desiree; Thackeray, James T; Daum, Guenter; Sohns, Jan M; Kropf, Saskia; Wester, Hans-Jürgen; Ross, Tobias L; Bengel, Frank M; Derlin, Thorsten

    2017-08-03

    The CXC-motif chemokine receptor 4 (CXCR4) represents a promising target for molecular imaging of different CXCR4+ cell types in cardiovascular diseases including atherosclerosis and arterial wall injury. The aim of this study was to assess the prevalence, pattern, and clinical correlates of arterial wall accumulation of (68)Ga-Pentixafor, a specific CXCR4 ligand for positron emission tomography (PET). Methods: Data of fifty-one patients who underwent (68)Ga-Pentixafor PET/computed tomography (PET/CT) for non-cardiovascular indications were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed qualitatively and semiquantitatively by blood-pool-corrected target-to-background ratios (TBRs). Tracer uptake was compared with calcified plaque burden and cardiovascular risk factors. Results: Focal arterial uptake of (68)Ga-Pentixafor was seen at 1411 sites in 51 (100%) of patients. (68)Ga-Pentixafor uptake was significantly associated with calcified plaque burden (P<0.0001) and cardiovascular risk factors including age (P<0.0001), arterial hypertension (P<0.0001), hypercholesterolemia (P = 0.0005), history of smoking (P = 0.01), and prior cardiovascular events (P = 0.0004). Both the prevalence (P<0.0001) and signal intensity (P = 0.009) of (68)Ga-Pentixafor uptake increased as the number of risk factors increased. Conclusion:(68)Ga-Pentixafor PET/CT is suitable for non-invasive, highly specific PET imaging of CXCR4 expression in the atherosclerotic arterial wall. Arterial wall (68)Ga-Pentixafor uptake is significantly associated with surrogate markers of atherosclerosis, and is linked to the presence of cardiovascular risk factors. (68)Ga-Pentixafor signal is higher in patients with a high-risk profile, and may hold promise for identification of vulnerable plaque. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  12. Insulin Resistance: A Proinflammatory State Mediated by Lipid-Induced Signaling Dysfunction and Involved in Atherosclerotic Plaque Instability

    Directory of Open Access Journals (Sweden)

    François Mach

    2008-06-01

    Full Text Available The dysregulation of the insulin-glucose axis represents the crucial event in insulin resistance syndrome. Insulin resistance increases atherogenesis and atherosclerotic plaque instability by inducing proinflammatory activities on vascular and immune cells. This condition characterizes several diseases, such as type 2 diabetes, impaired glucose tolerance (IGT, impaired fasting glucose (IFG, obesity, hypertension, dyslipidemia, and other endocrinopathies, but also cancer. Recent studies suggest that the pathophysiology of insulin resistance is closely related to interferences with insulin-mediated intracellular signaling on skeletal muscle cells, hepatocytes, and adipocytes. Strong evidence supports the role of free fatty acids (FFAs in promoting insulin resistance. The FFA-induced activation of protein kinase C (PKC delta, inhibitor kappaB kinase (IKK, or c-Jun N-terminal kinase (JNK modulates insulin-triggered intracellular pathway (classically known as PI3-K-dependent. Therefore, reduction of FFA levels represents a selective target for modulating insulin resistance.

  13. The time window of MRI of murine atherosclerotic plaques after administration of CB2 receptor targeted micelles: inter-scan variability and relation between plaque signal intensity increase and gadolinium content of inversion recovery prepared versus non-prepared fast spin echo

    NARCIS (Netherlands)

    te Boekhorst, B. C. M.; Bovens, S. M.; van de Kolk, C. W. A.; Cramer, M. J. M.; Doevendans, P. A. F. M.; ten Hove, M.; van der Weerd, L.; Poelmann, R.; Strijkers, G. J.; Pasterkamp, G.; van Echteld, C. J. A.

    2010-01-01

    Single fast spin echo scans covering limited time frames are mostly used for contrast-enhanced MRI of atherosclerotic plaque biomarkers. Knowledge on inter-scan variability of the normalized enhancement ratio of plaque (NER(plaque)) and relation between NER(plaque) and gadolinium content for

  14. Intravascular detection of microvessel infiltration in atherosclerotic plaques: An intraluminal extension of acoustic angiography

    Science.gov (United States)

    Martin, K. Heath

    Cardiovascular disease is the leading cause of death worldwide, surpassing both stroke and cancer related mortality with 17.5 million deaths in 2014 alone. Atherosclerosis is the build-up of fatty deposits within arteries and is responsible for the majority of cardiovascular related deaths. Over the past decade, research in atherosclerosis has identified that a key limitation in the appropriate management of the disease is detecting and identifying dangerous fatty plaque build-ups before they dislodge and cause major cardiovascular events, such as embolisms, stroke, or myocardial infarctions. It has been noted that plaques vulnerable to rupture have several key features that may be used to distinguish them from asymptomatic plaques. One key identifier of a dangerous plaque is the presence of blood flow within the plaque itself since this is an indicator of growth and instability of the plaque. Recently, a superharmonic imaging method known as "acoustic angiography" has been shown to resolve microvasculature with unprecedented quality and could be a possible method of detecting blood vessel infiltration within these plaques. This dissertation describes the material and methods used to move the application of "acoustic angiography" to a reduced form factor typical of intravascular catheters and to demonstrate its ability to detect microvasculature. The implementation of this approach is described in terms of the contrast agents used to generate superharmonic signals, the dual-frequency transducers to image them, and the hardware needed to operate them in order to establish how these design choices can impact the quality of the images produced. Furthermore, this dissertation demonstrates how image processing methods such as adaptive windowing or automated sound speed correction can further enhance image quality of vascular targets. The results of these chapters show how acoustic angiography may be optimized using engineering considerations both in signal acquisition

  15. High-Resolution magnetic resonance imaging of carotid atherosclerotic plaque; Hochaufloesende Bildgebung atherosklerotischer Gefaesswandlaesionen der Karotiden durch die Magnetresonanztomografie

    Energy Technology Data Exchange (ETDEWEB)

    Saam, T.; Reiser, M.; Nikolaou, K. [Inst. fuer Klinische Radiologie, Ludwig-Maximilians-Univ. Muenchen (Germany); Schoenberg, S.O. [Inst. fuer Klinische Radiologie, Klinikum Mannheim gGmbH, Universitaetsklinikum Medizinische Fakultaet Mannheim (Germany); Hatsukami, T.S. [Surgery, VA Puget Sound Health Care System and Univ. of Washington (United States); Yuan, C. [Radiology, Univ. of Washington (United States)

    2008-02-15

    Stroke is the third most common cause of mortality in the United States with an incidence rate of approximately 700 000 deaths per year. As a means to prevent cerebrovascular events, current concepts advocate endarterectomy or carotid stenting in patients with advanced carotid disease. Arterial stenosis alone has been shown to be a poor predictor of cardiovascular events and therefore both arterial stenosis and patient symptom status are taken as indications for interventional therapy. Several studies have shown that symptomatic subjects benefit more from a carotid endarterectomy than asymptomatic subjects: 3 - 6 carotid endarterectomies are needed to prevent one stroke per year in symptomatic subjects with > 70% stenosis compared to 14 - 17 carotid endarterectomies in asymptomatic patients with > 50% stenosis. It is commonly accepted today that factors other than the degree of luminal stenosis can determine a patient's symptom status, such as the composition or the superficial structure of atherosclerotic plaque. High-resolution magnetic resonance imaging has overcome the limitations of current angiographic techniques and has emerged as a leading non-invasive imaging modality for atherosclerotic disease, especially within carotid arteries and other large vessels. In this review, the state of the art in MRI of atherosclerosis is presented in terms of hardware and image acquisition protocols. Also, the results of validation studies for measuring lesion size, composition and inflammation will be summarized. Finally, the status of several clinical trials involving MRI of atherosclerosis will be reviewed. (orig.)

  16. Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression.

    Science.gov (United States)

    Shimizu, Yoichi; Hanzawa, Hiroko; Zhao, Yan; Fukura, Sagiri; Nishijima, Ken-Ichi; Sakamoto, Takeshi; Zhao, Songji; Tamaki, Nagara; Ogawa, Mikako; Kuge, Yuji

    2017-08-01

    Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis. However, IgG accumulates nonspecifically in atherosclerotic regions, and its accumulation mechanisms have not yet been clarified in detail. Therefore, we explored IgG accumulation mechanisms in atherosclerotic lesions and examined images of radiolabeled IgG for the diagnosis of atherosclerosis. Mouse IgG without specificity to biomolecules was labeled with technetium-99m via 6-hydrazinonicotinate to yield [(99m)Tc]IgG. ApoE(-/-) or C57BL/6J mice were injected intravenously with [(99m)Tc]IgG, and their aortas were excised 24 h after injection. After radioactivity measurement, serial aortic sections were autoradiographically and histopathologically examined. RAW264.7 macrophages were polarized into M1 or M2 and then treated with [(99m)Tc]IgG. The radioactivities in the cells were measured after 1 h of incubation. [(99m)Tc]IgG uptake in M1 macrophages was also evaluated after the pretreatment with an anti-Fcγ receptor (FcγR) antibody. The expression levels of FcγRs in the cells were measured by western blot analysis. [(99m)Tc]IgG accumulation levels in the aortas were significantly higher in apoE(-/-) mice than in C57BL/6J mice (5.1 ± 1.4 vs 2.8 ± 0.5 %ID/g, p IgG than M2 or M0 (nonpolarized) macrophages [2.2 ± 0.3 (M1) vs 0.5 ± 0.1 (M2), 0.4 ± 0.1 (M0) %dose/mg protein, p IgG accumulation in M1 macrophages was suppressed by pretreatment with the anti-FcγR antibody [2.2 ± 0.3 (nonpretreatment) vs 1.2 ± 0.2 (pretreatment) %ID/mg protein, p IgG accumulated in pro-inflammatory M1 macrophages via FcγRs in atherosclerotic lesions. Thus, the target biomolecule-independent imaging of active inflammation should be taken into account in the diagnosis of

  17. Cardiovascular magnetic resonance parameters of atherosclerotic plaque burden improve discrimination of prior major adverse cardiovascular events

    Directory of Open Access Journals (Sweden)

    Bansilal Sameer

    2009-04-01

    Full Text Available Abstract Aims Patients with prior major cardiovascular or cerebrovascular events (MACE are more likely to have future recurrent events independent of traditional cardiovascular disease risk factors. The purpose of this study was to determine if patients with traditional risk factors and prior MACE had increased cardiovascular magnetic resonance (CMR plaque burden measures compared to patients with risk factors but no prior events. Methods and Results Black blood carotid and thoracic aorta images were obtained from 195 patients using a rapid extended coverage turbo spin echo sequence. CMR measures of plaque burden were obtained by tracing lumen and outer vessel wall contours. Patients with prior MACE had significantly higher MR plaque burden (wall thickness, wall area and normalized wall index in carotids and thoracic aorta compared to those without prior MACE (Wall thickness carotids: 1.03 ± 0.03 vs. 0.93± 0.03, p = 0.001; SD wall thickness carotids: 0.137 ± 0.0008 vs. 0.102 ± 0.0004, p Conclusion A greater plaque burden and plaque eccentricity is prevalent among patients with prior MACE.

  18. Evaluation of carotid atherosclerotic plaque surface characteristics utilizing simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) technique.

    Science.gov (United States)

    Chen, Shuo; Zhao, Huilin; Li, Jifan; Zhou, Zechen; Li, Rui; Balu, Niranjan; Yuan, Chun; Chen, Huijun; Zhao, Xihai

    2017-08-02

    To evaluate the feasibility of the Simultaneous Noncontrast Angiography and intraPlaque hemorrhage (SNAP) technique in identification of carotid plaque surface characteristics compared with the conventional multicontrast vessel wall imaging protocol. Thirty symptomatic patients with carotid plaque were recruited and underwent carotid artery magnetic resonance imaging (MRI) (3.0T) using a conventional multicontrast protocol and SNAP sequence. As an intrinsic multicontrast sequence, SNAP could generate a gray blood reference (Ref) image set, a black blood corrected real (CR) image set, and a bright blood MR angiography (MRA) image set. A bright blood SNAP Ref2 image was implemented by combining Ref and MRA images for facilitating plaque surface characteristics evaluation. The presence/absence of calcification (CA), juxtaluminal calcification (JCA), and ulceration was assessed. The agreement between SNAP and multicontrast vessel wall protocol in identifying CA, JCA, and ulceration was analyzed using Cohen's kappa analysis. The interreader and intrareader reproducibility of SNAP imaging in identifying plaque surface characteristics was also assessed. Good to excellent agreement was found between SNAP and conventional multicontrast protocol in identifying CA (κ = 0.74, 95% confidence interval [CI]: 0.54-0.93), JCA (κ = 0.81, 95% CI: 0.66-0.97), and ulceration (κ = 0.82, 95% CI: 0.65-0.99). In addition, excellent intrareader and interreader reproducibility was found for SNAP imaging in identification of CA, JCA, and ulceration. SNAP imaging showed excellent agreement with multicontrast imaging and high reproducibility in identification of both JCA and ulceration, suggesting that SNAP imaging may be a time-efficient, alternative tool in identification of plaque surface characteristics in carotid arteries. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

  19. Atherosclerotic plaques in the internal carotid artery and associations with lung function assessed by different methods.

    Science.gov (United States)

    Frantz, Sophia; Nihlén, Ulf; Dencker, Magnus; Engström, Gunnar; Löfdahl, Claes-Göran; Wollmer, Per

    2012-03-01

    Previous studies on associations between reduced lung function and cardiovascular disease (CVD) have mainly been based on forced expiratory volume in 1-s (FEV(1) ) and vital capacity (VC). This study examined potential associations between five different lung function variables and plaques in the internal carotid artery (ICA). Subjects (n = 450) from a previous population-based respiratory questionnaire survey [current smokers without lower respiratory symptoms, subjects with a self-reported diagnosis of chronic obstructive pulmonary disease (COPD) and never-smokers without lower respiratory symptoms] were examined using spirometry, body plethysmography and measurements of diffusing capacity for CO (D(L,CO) ). Plaques in the ICA were assessed by ultrasonography. Two hundred and twenty subjects were current smokers, 139 ex-smokers and 89 never-smokers. COPD was diagnosed in 130 subjects (GOLD criteria). Plaques in the ICA were present in 231 subjects (52%). General linear analysis with adjustment for established risk factors for atherosclerosis, including C-reactive protein, showed that D(L,CO) was lower [77.4% versus 83.7% of predicted normal (PN), P = 0.014] and residual volume (RV) was higher (110.3% versus 104.8% of PN, P = 0.020) in subjects with than without plaques in the ICA. This analysis did not show any statistically significant association between plaques and FEV(1) or VC. The occurrence of plaques in the ICA was associated with low D(L,CO) and high RV, but not significantly with FEV(1) or COPD status. The results suggest that the relationships between reduced lung function, COPD and CVD are complex and not only linked to bronchial obstruction and low-grade systemic inflammation. © 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  20. Serial intravascular ultrasound assessment of changes in coronary atherosclerotic plaque dimensions and composition: an update

    DEFF Research Database (Denmark)

    Hartmann, Marc; Huisman, Jennifer; Böse, Dirk

    2011-01-01

    This manuscript reviews the use of serial intravascular ultrasound (IVUS) examination of coronary atherosclerosis in recent observational studies and randomized trials that revealed the effects of cholesterol-lowering and lipid-modifying therapies and offered novel insight into plaque progression...

  1. Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol

    Directory of Open Access Journals (Sweden)

    Walter Masson

    Full Text Available Abstract Background: Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance or with high remnant cholesterol levels could have a greater residual cardiovascular risk. Objectives: To determine the prevalence of lipid discordance in a primary prevention population and analyze the clinical variables associated with it; To investigate the association between lipid discordance and remnant cholesterol with the presence of carotid plaque. Methods: Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define “lipid discordance” if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were < 4.0 mmol/L. Ultrasound was used to assess carotid plaque occurrence. Multiple regression logistic models were performed. Results: The study included 772 patients (mean age 52 ± 11 years, 66% women. The prevalence of lipid discordance was 34%. Male sex and body mass index were independently associated with discordant lipid pattern. The prevalence of carotid plaque was higher in subjects with lipid discordance (40.2% vs. 29.2, p = 0.002. The multivariate analysis showed that the discordant lipid pattern was associated with the greater probability of carotid plaque (OR 1.58, 95% CI 1.08-2.34, p = 0.02. Similarly, a significant association between calculated remnant cholesterol and carotid plaque was found. Conclusion: Lipid discordance and presence of a higher level of calculated remnant cholesterol are associated with subclinical atherosclerosis. Our findings could be used to improve the residual cardiovascular risk evaluation.

  2. Feasibility of Vascular Endothelial Growth Factor Imaging in Human Atherosclerotic Plaque Using 89Zr-Bevacizumab Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Reza Golestani

    2013-06-01

    Full Text Available Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture. Cardiovascular molecular imaging can be used for the detection of rupture-prone plaques. Imaging with radiolabeled bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF-A, can depict VEGF levels corresponding to the angiogenic status in tumors. We determined the feasibility of 89Zr-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA specimens. Five CEA specimens were coincubated with 89Zr-bevacizumab and aspecific 111In-labeled IgG to determine the specificity of bevacizumab accumulation. In 11 CEA specimens, 89Zr-bevacizumab micro-positron emission tomography (PET was performed following 2 hours of incubation. Specimens were cut in 4 mm wide segments and were stained for VEGF and CD68. In each segment, the mean percent incubation dose per gram of tissue (%Inc/g and tissue to background ratio were determined. A 10-fold higher accumulation of 89Zr-bevacizumab compared to 111In-IgG uptake was demonstrated by gamma counting. The mean %Inc/ghot spot was 2.2 ± 0.9 with a hot spot to background ratio of 3.6 ± 0.8. There was a significant correlation between the segmental tissue to background uptake ratio and the VEGF score (ρ = .74, p < .001. It is feasible to detect VEGF tissue concentration within CEA specimens using 89Zr-bevacizumab PET. 89Zr-bevacizumab accumulation in plaques is specific and correlates with immunohistochemistry scores.

  3. Selective ablation of WHHLMI rabbit atherosclerotic plaque by quantum cascade laser in the 5.7 μm wavelength range for less-invasive laser angioplasty

    Science.gov (United States)

    Hashimura, Keisuke; Ishii, Katsunori; Akikusa, Naota; Edamura, Tadataka; Yoshida, Harumasa; Awazu, Kunio

    2013-06-01

    We investigated the potential of a compact and high-power quantum cascade laser (QCL) in the 5.7 μm wavelength range for less-invasive laser angioplasty. Atherosclerotic plaques consist mainly of cholesteryl esters. Radiation at a wavelength of 5.75 μm is strongly absorbed in C=O stretching vibration mode of cholesteryl esters. Our previous study achieved to make cutting differences between a normal artery and an atherosclerotic lesions using nanosecond pulsed laser by difference-frequency generation (DFG laser) at the wavelength of 5.75 μm. For applying this technique to clinical treatment, a compact laser device is required. In this study, QCL irradiation effects to a porcine normal aorta were compared with DFG laser. Subsequently, QCL irradiation effects on an atherosclerotic aorta of myocardial infarction-prone Watanabe heritable hyperlipidemic rabbit (WHHLMI rabbit) and a normal rabbit aorta were observed. As a result, the QCL could make cutting differences between the rabbit atherosclerotic and normal aortas. On the other hand, the QCL induced more thermal damage to porcine normal aorta than the DFG laser at the irradiation condition of comparable ablation depths. In conclusion, the possibility of less-invasive and selective treatment of atherosclerotic plaques using the QCL in the 5.7 μm wavelength range was revealed, although improvement of QCL was required to prevent the thermal damage of a normal artery.

  4. Thermal ablation of WHHLMI rabbit atherosclerotic plaque by quantum cascade laser in the 5.7-μm wavelength range

    Science.gov (United States)

    Hashimura, Keisuke; Ishii, Katsunori; Akikusa, Naota; Edamura, Tadataka; Yoshida, Harumasa; Awazu, Kunio

    2013-03-01

    We evaluated the utility of a compact and high-power quantum cascade laser (QCL) in the 5.7 μm wavelength range for less-invasive laser angioplasty. Atherosclerotic plaques mainly consist of cholesteryl esters. The wavelength of 5.75 μm is well absorbed in C=O stretching vibration mode of cholesteryl esters. Our previous study achieved to make cutting differences between a normal tunica intima of an artery and an atherosclerotic lesions using a nanosecond pulsed laser by difference-frequency generation (DFG laser) at the wavelength of 5.75 μm. For realizing a clinical application of this technique, a compact laser device is required. In this study, QCL irradiation effects to a porcine normal aorta were compared with DFG laser. In addition QCL irradiation effects to an atherosclerotic aorta of myocardial infarction-prone Watanabe heritable hyperlipidemic rabbit (WHHLMI rabbit) and a normal aorta were observed. As a result, the QCL could make cutting difference between the rabbit atherosclerotic aorta and the normal aorta. On the other hand, the QCL induced more thermal damage to porcine normal aorta than the DFG laser at the irradiation condition of comparable ablation depth. In conclusion, the possibility of less-invasive and selective treatment of atherosclerotic plaques using the QCL in the 5.7 μm wavelength range was revealed, although improvement of QCL was required to prevent the thermal damage of a normal artery.

  5. Role of Ox-LDL/LOX-1/NF-κB signaling pathway in regulation of atherosclerotic plaque growth by testosterone in male rabbits.

    Science.gov (United States)

    Li, Shijun; Guo, Yuanyuan; Zhu, Ping; Yang, Tingshu

    2013-01-01

    The purpose of our study is to investigate the role of oxidized low density lipoprotein (Ox-LDL)/lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1)/nuclear factor-κB (NF-κB) signaling pathway in the regulation of atherosclerotic plaque growth by testosterone in male atherosclerotic rabbits. The male rabbit model was prepared by castration and feeding cholesterol-rich diet. Pathological sections of thoracic aorta were performed hematoxylin-eosin staining to observe aortic morphological changes. Total serum testosterone was measured with chemical luminescent method. Serum Ox-LDL, soluble intercellular adhesion molecule-1 (sICAM-1) and matrix metalloproteinases-2 (MMP2) were assayed using ELISA kit following the manufacturer's instructions. Serum tumor necrosis factor α (TNFα) and interleukin-6 (IL6) were assayed using radioimmunoassay. Expressions of LOX-1 of thoracic aorta were measured by RT-PCR, immunohistochemistry and Western blot methods respectively. There was no significant difference in Ox-LDL level between all groups. The LOX-1 mRNA and protein expression of thoracic aorta were significantly higher in the castrated rabbits as compared with the sham-operated ones, and testosterone replacement could reduce the mRNA and protein expression of LOX-1 of thoracic aorta in the castrated rabbits. PIA reduced artery intima thickness and plaque area in castrated rabbits, which was further enhanced by testosterone replacement. PDTC reduced artery intima thickness and plaque area in castrated rabbits, which couldn't be enhanced by testosterone replacement. Our study demonstrates that testosterone can regulate atherosclerotic plaque progression, affect expression of LOX-1 and NF-κB in thoracic aorta and play a role in atherosclerotic plaque growth via NF-κB rather than Ox-LDL or LOX-1 in male rabbits. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Impact of Wall Shear Stress and Pressure Variation on the Stability of Atherosclerotic Plaque

    Science.gov (United States)

    Taviani, V.; Li, Z. Y.; Sutcliffe, M.; Gillard, J.

    Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady and unsteady conditions assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding one dimensional models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed linearly elastic, homogeneous isotropic. The analysis showed that wall shear stress is small (less than 3.5%) with respect to pressure drop throughout the cycle even for severe stenosis. On the contrary, the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by one dimensional models. This suggests that the primary source of mistakes in one dimensional studies comes from neglecting the three dimensional geometry of the plaque. Neglecting axial forces only involves minor errors.

  7. Induction of Dendritic Cell-Mediated Activation of T Cells From Atherosclerotic Plaques by Human Heat Shock Protein 60.

    Science.gov (United States)

    Rahman, Mizanur; Steuer, Johnny; Gillgren, Peter; Hayderi, Assim; Liu, Anquan; Frostegård, Johan

    2017-11-18

    Atherosclerosis is characterized by the presence of activated immune-competent cells including dendritic cells (DCs) and T cells, dead cells, and oxidized low-density lipoprotein. HSP60 (Heat shock protein 60) has been implicated in atherosclerosis. A plasma protein, Annexin A5, has atheroprotective properties. Human DCs differentiated from peripheral blood monocytes were treated with human HSP60 or HSP90 and autologous T cells were cocultured with these pretreated DCs (mDCs). HSP60 induced mDCs and T-cell activation as determined by FACScan (Fluorescence associated cell scan), gene-activation, and cytokine production. HSP60-induced T-cell activation was partly major histocompatibility complex class II-dependent. T cells exposed to HSP60-treated mDCs produced interferon-γ, interleukin-17, but not transforming growth factor-β. HSP60 did not promote expression of Toll-like receptors 2 or 4. HSP90 promoted mDCs maturation but had no effect on T-cell activation. Annexin A5 inhibited HSP60-proinflammatory Th1/Th17 effects on mDCs and T cells, and partly bound HSP60. Further, Annexin A5 inhibited HSP-induced activation of mDCs and also oxidized low-density lipoprotein-induced HSP-production from mDCs. Experiments on mDCs and T cells derived from carotid atherosclerotic plaques from patients with symptomatic carotid disease gave similar results as from blood donors. HSP60 induces mDCs activation and partly major histocompatibility complex class II-dependent activation of blood- and plaque-derived T cells, which is mostly of Th1/Th17 type. HSP60 could thus be an important T-cell antigen in plaques, and also mediate oxidized low-density lipoproteins immunogenic effects on DC-T-cell activation, promoting plaque rupture and clinical manifestations of cardiovascular disease. Annexin A5 inhibits both oxidized low-density lipoprotein-induced HSP60, and HSP60-mediated immune activation, which suggests a potential therapeutic role. © 2017 The Authors. Published on behalf of the

  8. Nuclear medicine and coronary artery disease: evaluation of tracers of myocardial perfusion and vulnerable atherosclerotic plaque; Medecine nucleaire et maladie coronarienne: evaluation de traceurs de la perfusion myocardique et de la plaque d'atherome vulnerable

    Energy Technology Data Exchange (ETDEWEB)

    Broisat, A

    2005-04-15

    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, {sup 201}Tl presents some drawbacks. {sup 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 {sup 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, {sup 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)

  9. A Method To Create Reference Maps for Evaluation of Ultrasound Images of Carotid Atherosclerotic Plaque

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Jensen, M. S.; Gammelmark, Kim

    2004-01-01

    , the blocks were decalcified, sliced, photographed and analyzed histologically. This gave a total of 123 slices. The plaque regions of the photographs were outlined and the outline adjusted to partly compensate for occasional displacement during slicing. Inside this outline, the material constitutions were...... found by incorporating the histologic information. From this set, slices with 1. too much tissue displacement due to cutting or 2. lack of identification of calcification as found by x ray, were removed. This resulted in 53 reference maps. The material types identified covered soft tissues, fibrous...

  10. Fluorescent lifetime imaging microscopy using Europium complexes improves atherosclerotic plaques discrimination.

    Science.gov (United States)

    Sicchieri, Letícia Bonfante; de Andrade Natal, Rodrigo; Courrol, Lilia Coronato

    2016-10-01

    The objective of this study is to characterize arterial tissue with and without atherosclerosis by fluorescence lifetime imaging microscopy (FLIM) using Europium Chlortetracycline complex (EuCTc) as fluorescent marker. For this study, twelve rabbits were randomly divided into a control group (CG) and an experimental group (EG), where they were fed a normal and hypercholesterolemic diet, respectively, and were treated for 60 days. Cryosections of the aortic arch specimens were cut in a vertical plane, mounted on glass slides, and stained with Europium (Eu), Chlortetracycline (CTc), Europium Chlortetracycline (EuCTc), and Europium Chlortetracycline Magnesium (EuCTcMg) solutions. FLIM images were obtained with excitation at 405 nm. The average autofluorescence lifetime within plaque depositions was ~1.36 ns. Reduced plaque autofluorescence lifetimes of 0.23 and 0.31 ns were observed on incubation with EuCTc and EuCTcMg respectively. It was observed a quenching of collagen, cholesterol and TG emission spectra increasing EuCTc concentration. The drastic reduction in fluorescence lifetimes is due to a resonant energy transfer between collagen, triglycerides, cholesterol and europium complexes, quenching fluorescence.

  11. Detection of coronary atherosclerotic plaques with superficial proteoglycans and foam cells using real-time intrinsic fluorescence spectroscopy.

    Science.gov (United States)

    Angheloiu, George O; Haka, Abigail S; Georgakoudi, Irene; Arendt, Joseph; Müller, Markus G; Scepanovic, Obrad R; Evanko, Stephen P; Wight, Thomas N; Mukherjee, Prasun; Waldeck, David H; Dasari, Ramachandra R; Fitzmaurice, Maryann; Kramer, John R; Feld, Michael S

    2011-03-01

    The protein components of low-density lipoprotein (LDL), oxidized LDL and proteoglycans such as versican contain tryptophan, an amino acid with characteristic fluorescence features at 308 nm excitation wavelength. We hypothesize that intrinsic fluorescence spectroscopy at 308 nm excitation wavelength IFS308, a method suitable for clinical use, can identify coronary artery lesions with superficial foam cells (SFCs) and/or proteoglycans. We subjected 119 human coronary artery specimens to in vitro fluorescence and reflectance spectroscopy. We used 5 basis spectra to model IFS308, and extracted their contributions to each individual IFS308 spectrum. A diagnostic algorithm using the contributions of Total Tryptophan and fibrous cap to IFS308 was built to identify specimens with SFCs and/or proteoglycans in their top 50 μm. We detected SFCs and/or proteoglycans, such as versican or the glycosaminoglycan hyaluronan, in 24 fibrous cap atheromas or pathologic intimal thickening (PIT) lesions. An algorithm using the contributions of Total Tryptophan and fibrous cap to IFS308 was able to identify these segments with 92% sensitivity and 80% specificity. We were able to establish a set of characteristic LDL, oxidized LDL, versican and hyaluronan fluorescence spectra, ready to be used for real-time diagnosis. The IFS(308) technique detects SFCs and/or proteoglycans in fibrous cap atheromas and PIT lesions. SFCs and proteoglycans are histological markers of vulnerable plaques, and this study is a step further in developing an invasive clinical tool to detect the vulnerable atherosclerotic plaque. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  12. 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

  13. Preferential pharmacological inhibition of macrophage ACAT increases plaque formation in mouse and rabbit models of atherogenesis.

    Science.gov (United States)

    Perrey, S; Legendre, C; Matsuura, A; Guffroy, C; Binet, J; Ohbayashi, S; Tanaka, T; Ortuno, J C; Matsukura, T; Laugel, T; Padovani, P; Bellamy, F; Edgar, A D

    2001-04-01

    The cholesteryl ester, foam cell-enriched vulnerable plaque is a principle pharmacological target for reducing athero-thrombosis. Acyl CoA:cholesterol Acyl Transferase (ACAT) catalyzes the esterification of free cholesterol in intestine, liver, adrenal and macrophages, leading in the latter cells to intracellular cholesteryl ester accumulation and foam cell formation in the arterial intima. Previous studies suggested the existence of several isoforms of ACAT with different tissue distribution and this has largely been confirmed by molecular cloning of ACAT-1 and ACAT-2. We developed a series of ACAT inhibitors that preferentially inhibited macrophage ACAT relative to hepatic or intestinal ACAT based on in vitro assays and ex vivo bioavailability studies. Four of these compounds were tested in three models of atherosclerosis at oral doses shown to give sufficient bioavailable monocyte/macrophage ACAT inhibitory activity. In fat-fed C57BL/6 mice, chow fed apo E-/- mice and KHC rabbits, the various ACAT inhibitors had either no effect or increased indices of atherosclerotic foam cell formation. Direct and indirect measurements suggest that the increase in plaque formation may have been related to inhibition of macrophage ACAT possibly leading to cytotoxic effects due to augmented free cholesterol. These results suggest that pharmacological inhibition of macrophage ACAT may not reduce, but actually aggravate, foam cell formation and progression.

  14. Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment

    Directory of Open Access Journals (Sweden)

    Manish Jain

    2016-09-01

    Full Text Available Photodynamic therapy (PDT, which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus this intra-arterial PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. Aim: We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®, efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Methods and Results: Visudyne® (100, 200 and 500 ng/ml was perfused for 5-30 minutes in atherosclerotic aorta isolated from ApoE-/- mice. The fluorescence Intensity (FI after 15 minutes of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8, 200 (FI-31.9 ± 1.9 or 500 ng/ml (FI-42.9 ± 1.2. Visudyne® (500 ng/ml uptake also increased with the administration time from 5 minutes (FI-9.8 ± 2.5 to 10 minutes (FI-23.3 ± 3.0 and 15 minutes (FI-42.9 ± 3.4 before reaching saturation at 30 minutes (FI-39.3 ± 2.4 contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm2, irradiance-334 mW/cm2 applied immediately after Visudyne® perfusion (500 ng/ml for 15 minutes using a cylindrical light diffuser coupled to a diode laser (690 nm, led to an increase of ROS (Dihydroethidium (FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9 and apoptotic cells (TUNEL (2.5 ± 1.6 %, 41.3 ± 15.3 %, 58.9 ± 6 %, mainly plaque macrophages (immunostaining (0.3 ± 0.2 %, 37.6 ± 6.4 %, 45.3 ± 5.4 % at light doses of 0, 100 or 200 J/cm2 respectively. Limited apoptosis was observed in the medial wall (0.5 ± 0.2 %, 8.5 ± 4.7 %, 15.3 ± 12.7 %. Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram. Conclusion: We demonstrated that sufficient accumulation of

  15. EC4, a truncation of soluble N-cadherin, reduces vascular smooth muscle cell apoptosis and markers of atherosclerotic plaque instability

    Directory of Open Access Journals (Sweden)

    Cressida A Lyon

    2014-01-01

    Full Text Available Atherosclerotic plaque instability is precipitated by vascular smooth muscle cell apoptosis in the fibrous cap, weakening it and leading to plaque rupture. We previously showed that reducing smooth muscle cell apoptosis with soluble N-cadherin (SNC increased features of plaque stability. We have now identified the active site of SNC and examined whether a truncated form containing this site retains the antiapoptotic effect. SNC was mutated to prevent interaction with N-cadherin or fibroblast growth factor receptor (FGFR. Interaction with FGFR in the extracellular (EC 4 domain of SNC was essential for the antiapoptotic effect. Therefore, we made a truncated form consisting of the EC4 domain. EC4 significantly reduced smooth muscle cell, macrophage, and endothelial cell apoptosis in vitro by ∼70%, similar to SNC. Elevation of plasma levels of EC4 in male apolipoprotein E–deficient mice with existing atherosclerosis significantly reduced apoptosis in brachiocephalic artery plaques by ∼50%. EC4 reduced plaque size and the incidence of buried fibrous layers and the macrophage:smooth muscle cell ratio (surrogate markers of plaque instability. Interaction of EC4 with FGFR induced potent antiapoptotic signaling in vitro and in vivo. EC4 modulates atherosclerosis in mice demonstrating its therapeutic potential for retarding plaque size and instability.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Quantitative colorimetry of atherosclerotic plaque using the L*a*b* color space during angioscopy for the detection of lipid cores underneath thin fibrous caps.

    Science.gov (United States)

    Ishibashi, Fumiyuki; Yokoyama, Shinya; Miyahara, Kengo; Dabreo, Alexandra; Weiss, Eric R; Iafrati, Mark; Takano, Masamichi; Okamatsu, Kentaro; Mizuno, Kyoichi; Waxman, Sergio

    2007-12-01

    Yellow plaques seen during angioscopy are thought to represent lipid cores underneath thin fibrous caps (LCTCs) and may be indicative of vulnerable sites. However, plaque color assessment during angioscopy has been criticized because of its qualitative nature. The purpose of the present study was to test the ability of a quantitative colorimetric system to measure yellow color intensity of atherosclerotic plaques during angioscopy and to characterize the color of LCTCs. Using angioscopy and a quantitative colorimetry system based on the L*a*b* color space [L* describes brightness (-100 to +100), b* describes blue to yellow (-100 to +100)], the optimal conditions for measuring plaque color were determined in three flat standard color samples and five artificial plaque models in cylinder porcine carotid arteries. In 88 human tissue samples, the colorimetric characteristics of LCTCs were then evaluated. In in-vitro samples and ex-vivo plaque models, brightness L* between 40 and 80 was determined to be optimal for acquiring b* values, and the variables unique to angioscopy in color perception did not impact b* values after adjusting for brightness L* by manipulating light or distance. In ex-vivo human tissue samples, b* value >/=23 (35.91 +/- 8.13) with L* between 40 and 80 was associated with LCTCs (fibrous caps <100 mum). Atherosclerotic plaque color can be consistently measured during angioscopy with quantitative colorimetry. High yellow color intensity, determined by this system, was associated with LCTCs. Quantitative colorimetry during angioscopy may be used for detection of LCTCs, which may be markers of vulnerability.

  18. Vascular endothelial growth factor (VEGF and monocyte chemoattractant protein (MCP-1 levels unaltered in symptomatic atherosclerotic carotid plaque patients from North India

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    Dheeraj eKhurana

    2013-04-01

    Full Text Available We aimed to identify the role of vascular endothelial growth factor(VEGF and monocyte chemoattractant protein(MCP-1 as a serum biomarker of symptomatic carotid atherosclerotic plaque in North Indian population. Individuals with symptomatic carotid atherosclerotic plaque have high risk of ischemic stroke. Previous studies from western countries have shown an association between VEGF and MCP-1 levels and the incidence of ischemic stroke. In this study, venous blood from 110 human subjects was collected, 57 blood samples of which were obtained from patients with carotid plaques, 38 neurological controls without carotid plaques and another 15 healthy controls who had no history of serious illness. Serum VEGF and MCP-1 levels were measured using commercially available enzyme-linked immunosorbent assay(ELISA. We also correlated the data clinically and carried out risk factor analysis based on the detailed questionnaire obtained from each patient. For risk factor analysis, a total of 70 symptomatic carotid plaque cases and equal number of age and sex matched healthy controls were analyzed. We found that serum VEGF levels in carotid plaque patients did not show any significant change when compared to either of the controls. Similarly, there was no significant upregulation of monocyte chemoattractant protein-1 in the serum of these patients. The risk factor analysis revealed that hypertension, diabetes, and physical inactivity were the main correlates of carotid atherosclerosis(p<0.05. Prevalence of patients was higher residing in urban areas as compared to rural region. We also found that patients coming from mountaineer region were relatively less vulnerable to cerebral atherosclerosis as compared to the ones residing at plain region. We conclude that the pathogenesis of carotid plaques may progress independent of these inflammatory molecules. In parallel, risk factor analysis indicates hypertension, diabetes and sedentary lifestyle as the most

  19. The effect of interleukin and matrix metalloproteinase on the vulnerability of carotid atherosclerotic plaque and cerebral infarction

    Directory of Open Access Journals (Sweden)

    HUANG Yan

    2012-06-01

    Full Text Available Objective To investigate the relationship of IL-17, IL-10 and MMP-12 with the vulnerability of carotid atherosclerotic plaque and cerebral infarction. Methods According to clinical stroke event 70 carotid atherosclersis patients were divided into asymptomatic carotid atherosclerosis (ACAS group (n = 35 and acute atherosclerotic cerebral infarction (AACI group (n = 35. The patients were also divided into vulnerable plague (VP group (n = 38 and unvulnerable plague (UVP group (n = 32 by color ultrasonic technique. Normal control group (n = 35 was established. The plasma levels of cytokines were tested by enzyme-linked immunosorbent assay (ELISA. Results Compared with the control group, the concentrations of IL-17, IL-10 and MMP-12 in ACAS group and AACI group were significantly elevated (P = 0.000; P = 0.000, moreover, the concentrations of IL-17 and MMP-12 in AACI group were higher than those in ACAS group (P = 0.000; P = 0.002, respectively. In AACI group, the level of IL-10 was lower than the ACAS group and control group (P = 0.000, for all, whereas, no significant difference of IL-10 level was seen between ACAS group and control group (P = 0.275. In VP group, the concentrations of IL-17 and MMP-12 were higher than those in UVP group (P = 0.000 and 0.014, respectively. In VP group, the level of IL-10 was lower than that in UVP group and control group (P = 0.000, for all, but no significant difference of IL-10 level was seen between UVP group and control group (P = 0.742. Correlation analysis showed, the level of IL-17 was positively correlated with the level of MMP-12 (r = 0.640, P = 0.000, and was negatively correlated with the level of IL-10 (r =-0.430, P = 0.000. The level of MMP-12 was weakly negatively correlated with the level of IL-10 (r =-0.242, P = 0.013. Conclusion IL-17, IL-10 and MMP-12 all participate the pathological process of atherosclerosis and cerebral infarction. The elevated IL-17 and MMP-12 levels and decreased IL-10 level

  20. 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...... prospectively assessed by 18-FDG (inflammation) and Sodium 18-Fluoride (Na-18F) (calcification metabolism) PET CT imaging. Global aortic uptake of 18-FDG and Na-18F was quantified by subtracting the blood pool SUVmean from the aortic SUVmax (cSUV) [maximum SUVaorta - mean SUVblood pool]. Calculating regression...... 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...

  1. Early dental plaque formation on toothbrushed titanium implant surfaces.

    Science.gov (United States)

    Amarante, Evandro Scligliano; Chambrone, Leandro; Lotufo, Roberto Fraga Moreira; Lima, Luiz A

    2008-10-01

    To evaluate the qualitative and quantitative differences on dental plaque formation on two different roughness titanium implant surfaces, i.e. machined and titanium plasma sprayed, as well as the amount of plaque removal by regular toothbrushing after 72-hour plaque accumulation. Eight systemically healthy subjects were recruited from the patient pool of a private dental practice. All patients underwent oral hygiene instruction and full mouth prophylaxis. Subsequently, maxillary casts from all patients were obtained and removable 0.7 mm-thick acetate stents without occlusal contact points were fabricated to support four titanium specimens of 4 x 2 x 2 mm divided into two groups (machined and plasma sprayed). Subjects were instructed to wear the stents for 72 hours, full time, removing them only during regular oral hygiene. Subsequently, the appliances were immediately repositioned and then the test side was brushed for 20 seconds. At the end of the 72-hour period, the stents were removed and prepared for microbiological analysis. Both machined and plasma sprayed brushed surfaces presented statistically significant fewer bacteria than non-brushed surfaces. Similarly, regarding surface roughness, machined surfaces presented a total number of bacteria significantly smaller than those presented by plasma sprayed surfaces (P dental plaque than polished surfaces. Both brushed surfaces presented less plaque accumulation, however, implant brushing was more effective on machined surfaces.

  2. Multicontrast-weighted magnetic resonance imaging of atherosclerotic plaques at 3.0 and 1.5 Tesla: ex-vivo comparison with histopathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Koops, Andreas; Ittrich, Harald; Priest, Andrew; Stork, Alexander; Adam, Gerhard; Weber, Christoph [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Petri, Susan [University Medical Center Hamburg-Eppendorf, Department of Pathology, Hamburg (Germany); Lockemann, Ute [University Medical Center Hamburg-Eppendorf, Department of Forensic Medicine, Hamburg (Germany)

    2007-01-15

    The purpose was to analyze magnetic resonance (MR) plaque imaging at 3.0 Tesla and 1.5 Tesla in correlation with histopathology. MR imaging (MRI) of the abdominal aorta and femoral artery was performed on seven corpses using T1-weighted, T2-weighted, and PD-weighted sequences at 3.0 and 1.5 Tesla. Cross-sectional images at the branching of the inferior mesenteric artery and the profunda femoris were rated with respect to image quality. Corresponding cross sections of the imaged vessels were obtained at autopsy. The atherosclerotic plaques in the histological slides and MR images were classified according to the American Heart Association (AHA) and analyzed for differences. MRI at 3.0 Tesla offered superior depiction of arterial wall composition in all contrast weightings, rated best for T2-weighted images. Comparing for field strength, the highest differences were observed in T1-weighted and T2-weighted techniques (both P{<=}0.001), with still significant differences in PD-weighted sequence (P{<=}0.005). The majority of plaques were histologically classified as calcified plaques. In up to 21% of the cases, MRI at both field strengths detected signal loss characteristic of calcification although calcified plaque was absent in histology. MRI at 3.0 Tesla offers superior plaque imaging quality compared with 1.5 Tesla, but further work is necessary to determine whether this translates in superior diagnostic accuracy. (orig.)

  3. Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol.

    Science.gov (United States)

    Masson, Walter; Lobo, Martín; Molinero, Graciela; Siniawski, Daniel

    2017-06-01

    Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance) or with high remnant cholesterol levels could have a greater residual cardiovascular risk. To determine the prevalence of lipid discordance in a primary prevention population and analyze the clinical variables associated with it; To investigate the association between lipid discordance and remnant cholesterol with the presence of carotid plaque. Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define "lipid discordance" if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were colesterol remanescente poderiam ter maior risco cardiovascular residual. determinar a prevalência de discordância lipídica em uma população de prevenção primária e analisar as variáveis clínicas com ela associadas; investigar a associação de discordância lipídica e colesterol remanescente calculado com a presença de placa carotídea. Pacientes de prevenção primária sem diabetes ou sem terapia hipolipemiante foram incluídos. Independentemente do nível de LDL-C, definiu-se "discordância lipídica" como um valor de não HDL-C excedendo em 30 mg/dl aquele de LDL-C. Calculou-se o colesterol remanescente como colesterol total menos HDL-C menos LDL-C na presença de triglicerídeos colesterol remanescente calculado e placa carotídea. Discordância lipídica e presença de nível mais alto de colesterol remanescente calculado acham-se associados com aterosclerose subclínica. Nossos achados podem ser usados para aprimorar a avaliação de risco cardiovascular residual.

  4. {sup 18}F-FDG PET and intravascular ultrasonography (IVUS) images compared with histology of atherosclerotic plaques: {sup 18}F-FDG accumulates in foamy macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Ishino, Seigo [Takeda Pharmaceutical Company Limited, Pharmaceutical Research Division, Fujisawa (Japan); Takeda Pharmaceutical Company Limited, Biomolecular Research Laboratories, Pharmaceutical Research Division, Fujisawa, Kanagawa (Japan); Ogawa, Mikako; Magata, Yasuhiro [Hamamatsu University School of Medicine, Medical Photonics Research Center, Hamamatsu (Japan); Mori, Ikuo; Nishimura, Satoshi; Ikeda, Shota; Sugita, Taku; Oikawa, Tatsuo; Horiguchi, Takashi [Takeda Pharmaceutical Company Limited, Pharmaceutical Research Division, Fujisawa (Japan)

    2014-04-15

    Intravascular ultrasonography (IVUS) and {sup 18}F-FDG PET have been used to evaluate the efficacy of antiatherosclerosis drugs. These two modalities image different characteristics of atherosclerotic plaques, and a comparison of IVUS and PET images with histology has not been performed. The aim of this study was to align IVUS and PET images using anatomic landmarks in Watanabe heritable hyperlipidaemic (WHHL) rabbits, enabling comparison of their depiction of aortic atherosclerosis. Cellular {sup 18}F-FDG localization was evaluated by {sup 3}H-FDG microautoradiography (micro-ARG). A total of 19 WHHL rabbits (7 months of age) were divided into three groups: baseline (n = 6), 3 months (n = 4), and 6 months (n = 9). PET, IVUS and histological images of the same aortic segments were analysed. Infiltration by foamy macrophages was scored from 0 to IV using haematoxylin and eosin (H and E) and antimacrophage immunohistochemical staining, and compared with {sup 3}H-FDG micro-ARG findings in two additional WHHL rabbits. IVUS images did not identify foamy macrophage deposition but revealed the area of intimal lesions (r = 0.87). {sup 18}F-FDG PET revealed foamy macrophage distribution in the plaques. The intensity of {sup 18}F-FDG uptake was correlated positively with the degree of foamy macrophage infiltration. Micro-ARG showed identical {sup 3}H-FDG accumulation in the foamy macrophages surrounding the lipid core of the plaques. F-FDG PET localized and quantified the degree of infiltration of foamy macrophages in atherosclerotic lesions. IVUS defined the size of lesions. {sup 18}F-FDG PET is a promising imaging technique for evaluating atherosclerosis and for monitoring changes in the composition of atherosclerotic plaques affecting their stability. (orig.)

  5. Chocolate Consumption is Inversely Associated with Calcified Atherosclerotic Plaque in the Coronary Arteries: The NHLBI Family Heart Study

    Science.gov (United States)

    Djoussé, Luc; Hopkins, Paul N.; Arnett, Donna K.; Pankow, James S.; Borecki, Ingrid; North, Kari E.; Ellison, R. Curtis

    2010-01-01

    Background and Aims While a diet rich in anti-oxidant has been favorably associated with coronary disease and hypertension, limited data have evaluated the influence of such diet on subclinical disease. Thus, we sought to examine whether chocolate consumption is associated with calcified atherosclerotic plaque in the coronary arteries (CAC). Methods In a cross-sectional design, we studied 2,217 participants of the NHLBI Family Heart Study. Chocolate consumption was assessed by a semi-quantitative food-frequency questionnaire and CAC was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Results There was an inverse association between frequency of chocolate consumption and prevalent CAC. Odds ratios (95% CI) for CAC were 1.0 (reference), 0.94 (0.66-1.35), 0.78 (0.53-1.13), and 0.68 (0.48-0.97) for chocolate consumption of 0, 1-3 times per month, once per week, and 2+ times per week, respectively (p for trend 0.022), adjusting for age, sex, energy intake, waist-hip ratio, education, smoking, alcohol consumption, ratio of total-to-HDL-cholesterol, non-chocolate candy, and diabetes mellitus. Controlling for additional confounders did not alter the findings. Exclusion of subjects with coronary heart disease or diabetes mellitus did not materially change the odds ratio estimates but did modestly decrease the overall significance (p = 0.07). Conclusions These data suggest that chocolate consumption might be inversely associated with prevalent CAC. PMID:20655129

  6. Correlation of three grades with carotid atherosclerotic plaque by the ultrasound in middle-aged patients with hypertension

    Directory of Open Access Journals (Sweden)

    Jian-Ping Ru

    2017-01-01

    Full Text Available Objective: To explore the correlation of different hypertension grades with carotid atherosclerotic plaque in middle-aged patients with hypertension. Methods: A total of 300 patients with primary hypertension who were admitted in the Cardiology Department and Neurology Department of our hospital from January, 2015 to September, 2016 were included in the study and divided into 3 groups with 100 cases in each group according to the hypertension grade criteria. Moreover, 100 normal individuals who came for physical examinations were served as the control group. TCD was used to detect MCA, ACA, PCA, VA1, and BA. CDFI was used to detect CCA, ICA, ECA, and VA2. EDV, PSV, PI, and RI were detected, respectively. The nitrate reductase colorimetric method was used to detect NO, MDA, and SOD. Results: PSV and EDV in the internal carotid artery system in patients with hypertension were significantly reduced (P<0.05, while PI and RI were significantly increased (P<0.05; moreover, with the increasing of hypertension grading, PSV and EDV were gradually reduced, while PI and RI were increased. PSV and EDV in the vertebral artery system in patients with hypertension were significantly reduced (P<0.05, while PI and RI were significantly increased (P<0.05; moreover, with the increasing of hypertension grading, PSV and EDV were gradually reduced, while PI and RI were increased. SOD and NO in patients with hypertension were significantly lower than those in the control group (P<0.05, while MDA was significantly higher than that in the control group (P<0.05; moreover, with the increasing of hypertension grading, SOD and NO were gradually reduced, while MDA was gradually increased. Conclusions: TCD in combined with CDFI can make a comprehensive evaluation of hemodynamic indicators of intracranial and extracranial vessels in patients with hypertension, and is of great significance in the early detection of intracranial and extracranial arteriosclerosis.

  7. Serum 25-Hydroxyvitamin D3 Levels Are Associated with Carotid Intima-Media Thickness and Carotid Atherosclerotic Plaque in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Yurong Wang

    2017-01-01

    Full Text Available Objective. To investigate the relationship between serum 25-hydroxyvitamin D3 [25(OHD3] levels and carotid intima-media thickness (IMT as well as carotid atherosclerotic plaque in patients with type 2 diabetes mellitus (T2DM. Methods. 314 patients with T2DM were enrolled in this study. The clinical data and laboratory examinations of subjects were recorded, such as serum 25(OHD3, hemoglobin A1c (HbA1c, serum lipids, fasting blood glucose (FBG, and other biochemical parameters. Color Doppler ultrasound was used to measure carotid IMT and carotid atherosclerotic plaques. Patients were divided into four quartile groups according to the serum 25(OHD3 levels from low to high: group Q1~group Q4. Results. From group Q1 to group Q4, carotid IMT and the incidence of plaque were gradually reduced. Serum 25(OHD3 levels were lower in the plaque group compared with the nonplaque group (P<0.01. Serum 25(OHD3 levels were negatively correlated with the carotid IMT (r=−0.4, P<0.01. Multiple linear stepwise regression analysis showed that serum 25(OHD3 was independently associated with carotid IMT (β=−0.009, P<0.01. Logistic regression analysis showed that serum 25(OHD3 levels were independently associated with the presence of carotid plaque in T2DM (OR = 0.95; 95%CI: 0.92~0.98, P=0.004. Conclusions. Low vitamin D status may contribute to the incidence of carotid atherosclerosis in type 2 diabetic patients.

  8. Characterization of atherosclerotic plaque of carotid arteries with histopathological correlation: Vascular wall MR imaging vs. color Doppler ultrasonography (US)

    National Research Council Canada - National Science Library

    Watanabe, Yuji; Nagayama, Masako; Suga, Tsuyoshi; Yoshida, Kazumichi; Yamagata, Sen; Okumura, Akira; Amoh, Yoshiki; Nakashita, Satoru; Van Cauteren, Marc; Dodo, Yoshihiro

    2008-01-01

    To investigate whether the vessel wall MRI of carotid arteries would differentiate at-risk soft plaque from solid fibrous plaque by identifying liquid components more accurately than color Doppler ultrasonography (US...

  9. C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human Atherosclerotic Plaques

    DEFF Research Database (Denmark)

    Pilely, Katrine; Fumagalli, Stefano; Rosbjerg, Anne

    2017-01-01

    was the strongest mediator of C1q binding and also the pentraxin that most potently elevated C1q-mediated complement activation. In a phagocytic assay using whole blood, we confirmed that phagocytosis of CC is complement dependent and initiated by C1q-mediated activation. The pathophysiological relevance......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 serum...

  10. Inhibition of dental plaque formation by toothpaste containing propolis

    Directory of Open Access Journals (Sweden)

    Nurin Aisyiyah Listyasari

    2012-12-01

    Full Text Available Background: Plaque is the main cause of caries and periodontal disease. Caries and periodontal disease can be prevented by inhibiting dental plaque formation. To inhibit the formation of plaque, teeth must be brushed with toothpaste. According to previous studies, propolis contains apigenin and tt-farnesol classified as flavonoid that can inhibit the formation of dental plaque by inhibiting glucosyltransferase enzym and membrane integrity of Streptococcus mutans. Purpose: The aim of this study was to determine the effect of toothpaste containing propolis on the formation of dental plaque. Methods: Post test with only control group design was used. The subjects of this study were 30 boarding school students of Hidayatullah, Yayasan Al-Burhan, Gedawang, Semarang, divided into two groups, randomized control group and treatment group. Control group was not treated with toothpaste contanining propolis. Meanwhile, treatment group was treated with toothpaste containing propolis. Plaque then was measured by using plaque index of Sillness and Loe method after using toothpaste containing propolis for four hours. Afterwards, the data was analyzed by a computer program, Mann-Whitney test, with its significance p < 0.05. Results: The result of Mann-Whitney test showed a significant difference, 0.002 (p < 0.05, between the control group and the treatment group. The median of the control group was about 3.41, while that of the treatment group was about 0.58. Conclusion: The use of toothpaste contaning propolis can prevent dental plaque formation.Latar belakang: Plak merupakan penyebab utama terjadinya karies dan penyakit periodontal. Karies dan penyakit periodontal dapat dicegah dengan menghambat pembentukan plak gigi. Untuk mencegah terbentuknya plak, gigi harus digosok menggunakan pasta gigi. Penelitian terdahulu menyebutkan bahwa propolis mengandung flavonoid apigenin dan tt-farnesol yang mampu menghambat aktivitas enzim glukosiltransferase dan menghambat

  11. Imaging of inflamed carotid artery atherosclerotic plaques with the use of {sup 99m}Tc-HYNIC-IL-2 scintigraphy in end-stage renal disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Opalinska, Marta; Pach, Dorota; Sowa-Staszczak, Anna; Glowa, Boguslaw; Hubalewska-Dydejczyk, Alicja [Jagiellonian University Medical School, Nuclear Medicine Unit, Department of Endocrinology, Cracow (Poland); Stompor, Tomasz [University of Warmia and Mazury in Olsztyn, Department of Nephrology, Hypertensiology and Internal Medicine, Faculty of Medicine, Olsztyn (Poland); Mikolajczak, Renata; Garnuszek, Piotr; Maurin, Michal; Karczmarczyk, Urszula [National Centre for Nuclear Research Radioisotope Centre POLATOM, Otwock (Poland); Fedak, Danuta [Jagiellonian University Medical School, Clinical Biochemistry, Cracow (Poland); Krzanowski, Marcin; Sulowicz, Wladyslaw [Jagiellonian University Medical School, Department of Nephrology, Cracow (Poland); Rakowski, Tomasz [Jagiellonian University Medical School, 2nd Department of Cardiology, Institute of Cardiology, Cracow (Poland)

    2012-04-15

    Identification of vulnerable plaques remains crucial for better cardiovascular risk assessment. At least 20% of inflammatory cells within unstable (vulnerable) plaques comprise T lymphocytes, which contain receptors for interleukin-2 (IL-2); those receptors can be identified by scintigraphy with radiolabelled IL-2.The aim of this study was to identify the ''inflamed'' (vulnerable) plaques by scintigraphy using IL-2 labelled with {sup 99m}Tc in the selected, high cardiovascular risk group of end-stage renal disease (ESRD) patients. A total of 28 patients (18 men, 10 women, aged 55.2 {+-} 9.6 years, 17 on peritoneal dialysis, 11 on haemodialysis) underwent common carotid artery (CCA) scintigraphy with the use of {sup 99m}Tc-hydrazinonicotinamide (HYNIC)-IL-2. In all cases, ultrasound examination of the CCA was performed and levels of selected proinflammatory factors, atherogenic markers and calcium-phosphate balance parameters were measured. Finally, the target to non-target (T/nT) ratio of IL-2 uptake in atherosclerotic plaques with intima-media thickness (IMT), classic cardiovascular risk factors and concentrations of the measured factors were compared. Increased {sup 99m}Tc-HYNIC-IL-2 uptake in atherosclerotic plaques in 38/41 (91%) cases was detected. The median T/nT ratio of focal {sup 99m}Tc-HYNIC-IL-2 uptake in atherosclerotic plaques was 2.35 (range 1.23-3.63). The mean IMT value on the side of plaques assessed by scintigraphy was 0.79 {+-} 0.18 mm (median 0.8, range 0.5-1.275). Correlations between T/nT ratio and homocysteine (R = 0.22, p = 0.037), apolipoprotein B (apoB) (R = 0.31, p = 0.008), apoB to apoA-I ratio (R = 0.29, p = 0.012) and triglyceride concentration (R = 0.26, p = 0.021) were detected. A lower T/nT ratio in patients with better parameters of nutritional status (haemoglobin, albumin, adiponectin) in comparison with patients with worse nutritional parameters (3.20 {+-} 0.5 vs 2.16 {+-} 0.68, p = 0.025) was revealed as well

  12. Bi-modal imaging of atherosclerotic plaques: Automated method for co-registration between fluorescence lifetime imaging and intravascular ultrasound data

    Science.gov (United States)

    Gorpas, Dimitris; Fatakdawala, Hussain; Bec, Julien; Ma, Dinglong; Yankelevich, Diego R.; Bishop, John W.; Qi, Jinyi; Marcu, Laura

    2014-03-01

    The risk of atherosclerosis plaque rupture cannot be assessed by the current imaging systems and thus new multi-modal technologies are under investigation. This includes combining a new fluorescence lifetime imaging (FLIm) technique, which is sensitive to plaque biochemical features, with conventional intravascular ultrasound (IVUS), which provides information on plaque morphology. In this study we present an automated method allowing for the co-registration of imaging data acquired based on these two techniques. Intraluminal studies were conducted in ex-vivo segments of human coronaries with a multimodal catheter integrating a commercial IVUS (40 MHz) and a rotational side-viewing fiber based multispectral FLIm system (355 nm excitation, 390+/-20, 452+/-22 and 542+/-25 nm acquisition wavelengths). The proposed method relies on the lumen/intima boundary extraction from the IVUS polar images. Image restoration is applied for the noise reduction and edge enhancement, while gray-scale peak tracing over the A-lines of the IVUS polar images is applied for the lumen boundary extraction. The detection of the guide-wire artifact is used for the angular registration between FLIm and IVUS data, after which the lifetime values can be mapped onto the segmented lumen/intima interface. The segmentation accuracy has been assessed against manual tracings, providing 0.120+/-0.054 mm mean Hausdorff distance. This method makes the bi-modal FLIm and IVUS approach feasible for comprehensive intravascular diagnostic by providing co-registered biochemical and morphological information about atherosclerotic plaques.

  13. Selective expansion of influenza A virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques

    NARCIS (Netherlands)

    T.T. Keller (Tymen); J.J. van der Meer (Jelger); P. Teeling (Peter); K.F. van der Sluijs (Koenraad); M.M. Idu (Mirza); G.F. Rimmelzwaan (Guus); M. Levi (Michael); A.C. van der Wal (Allard); O.J. de Boer (Onno)

    2008-01-01

    textabstractBACKGROUND 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

  14. Intensive lipid lowering therapy with titrated rosuvastatin yields greater atherosclerotic aortic plaque regression: Serial magnetic resonance imaging observations from RAPID study.

    Science.gov (United States)

    Yogo, Makiko; Sasaki, Makoto; Ayaori, Makoto; Kihara, Teruyoshi; Sato, Hiroki; Takiguchi, Shunichi; Uto-Kondo, Harumi; Yakushiji, Emi; Nakaya, Kazuhiro; Komatsu, Tomohiro; Momiyama, Yukihiko; Nagata, Masayoshi; Mochio, Soichiro; Iguchi, Yasuyuki; Ikewaki, Katsunori

    2014-01-01

    Although previous randomized clinical trials established a basis for lipid guidelines worldwide, they employed fixed doses of statins throughout trials (fire-and-forget approach). In the real clinical setting, however, statin doses are titrated to achieve target low-density lipoprotein cholesterol (LDL-C) levels (treat-to-target approach). The major objective was to investigate whether intensive lipid-lowering therapy using the treat-to-target approach yielded greater regression of aortic plaques. We therefore performed a prospective, randomized trial comparing the effects of standard (achieve LDL-C levels recommended by the Japanese guidelines) and intensive (achieve 30% lower LDL-C levels than standard) rosuvastatin therapy for 1 year in 60 hypercholesterolemic patients with a primary endpoint of aortic atherosclerotic plaques evaluated by non-invasive magnetic resonance imaging (MRI). Average doses were 2.9 ± 3.1 and 6.5 ± 5.1 mg/day for standard (n = 29) and intensive therapy group (n = 31), respectively. Although both therapies significantly reduced LDL-C and high-sensitivity C-reactive protein (hsCRP) levels, LDL-C reduction was significantly greater in the intensive group (-46 vs. -34%). MRI study showed that thoracic aortic plaques were significantly regressed in both groups, with greater regression of thoracic plaque in the intensive group (-9.1 vs. -3.2%, p = 0.01). Multivariate analyses revealed that thoracic plaque regression was significantly correlated with hsCRP reduction, but not with changes in serum lipids, endothelial function, or doses of rosuvastatin. Intensive statin therapy with titration targeting lower LDL-C levels resulted in greater thoracic aortic plaque regression compared to standard therapy, which was correlated with hsCRP reduction, suggesting that intensive statin therapy could provide better clinical outcomes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. 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.

  16. Porphyromonas gingivalis Induced Fragmentation of Type IV Collagen Through Macrophage-Activated MMP-9: (In Vitro Study of Collagenolytic Mechanism in Pathogenesis of Atherosclerotic Plaque Rupture

    Directory of Open Access Journals (Sweden)

    Siti Nurul Mubarokah

    2009-12-01

    Full Text Available BACKGROUND: Periodontitis is caused mostly by Porphyromonas gingivalis (P.gingivalis and it is related to acute coronary syndrome. P.gingivalis  readily invades blood circulation and potentially induces collagenolytic activity of inflammatory cells that results in collagen vascular degradation leading to atherosclerotic plague rupture (APR. APR is responsible for the occurence of fatal cardiovascular events such as acute myocardial infraction (AMI. AIMS: To show that P.gingivalis potentially induces fragmentation of the type IV vascular collagen due to macrophage-activated MMP-9. METHODS: The ability of P.gingivalis to induce the type IV collagen fragmentation, shown by digesting type IV collagen with the supernatant of monocyte-derived macrophage activated by exposure to P.gingivalis suspension for 18 hours, 37oC, 5% CO2. The type IV collagen fragments were analyzed by SDS-PAGE and confirmed by Western-blotting. Antibody of type IV collagen produced and confirmed by dot-blotting prior to its being used as primary antibody of Western-blotting. The existence of MMP-9 was detected by Dot-blot and Western-blot technique, while the MMP-9 activity was assessed by SDS-PAGE and zymograms. RESULTS: Our data showed that P.gingivalis induced macrophage to produce MMP-9 as one of collagenolytic components, and interaction with P.gingivalis proteases enhanced the proteolytic activity and resulted in degradation of type IV collagen with molecular weight of 88 kDa into two smaller fragments with molecular weight of 80 kDa and 60 kDa. CONCLUSIONS: P.gingivalis induced macrophage to activate its MMP-9 that led to fragmentation of vascular type IV collagen in the pathogenesis of atherosclerotic plaque rupture. KEYWORDS: P.gingivalis, macrophage, type IV collagen fragmentation, atherosclerotic plaque rupture, AMI.

  17. Carotid atherosclerotic plaque progression and change in plaque composition over time: A 5-year follow-up study using serial ct angiography

    NARCIS (Netherlands)

    M.J. van Gils (Marjon); D. Vukadinovic (Danijela); A.C. Nouwens- van Dijk (Anouk); D.W.J. Dippel (Diederik); W.J. Niessen (Wiro); A. van der Lugt (Aad)

    2012-01-01

    textabstractBACKGROUND AND PURPOSE: Serial in vivo imaging of atherosclerosis is important for understanding plaque progression and is potentially useful in predicting cardiovascular events and monitoring treatment efficacy. This prospective study aims to quantify temporal changes in carotid

  18. Pregnancy associated plasma protein-A (PAPP-A) is not a marker of the vulnerable atherosclerotic plaque

    DEFF Research Database (Denmark)

    Iversen, Kasper K; Teisner, Ane Søgaard; Dalager, Soren

    2011-01-01

    OBJECTIVE: To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A. DESIGN AND METHODS: Vulnerable plaques and control tissues were examined by immunohistochemistry. Volunteers...

  19. ACAT inhibition reduces the progression of pre-existing, advanced atherosclerotic mouse lesions without plaque or systemic toxicity

    Science.gov (United States)

    Rong, James X.; Blachford, Courtney; Feig, Jonathan E.; Bander, Ilda; Mayne, Jeffrey; Kusunoki, Jun; Miller, Christine; Davis, Matthew; Wilson, Martha; Dehn, Shirley; Thorp, Edward; Tabas, Ira; Taubman, Mark B.; Rudel, Lawrence L.; Fisher, Edward A.

    2013-01-01

    Objective Acyl-CoA:cholesterol acyltransferase (ACAT) converts cholesterol to cholesteryl esters in plaque foam cells. Complete deficiency of macrophage ACAT has been shown to increase atherosclerosis in hypercholesterolemic mice due to cytotoxicity from free cholesterol accumulation, while we previously showed that partial ACAT inhibition by Fujirebio compound F1394 decreased early atherosclerosis development. In this report, we tested F1394 effects on pre-established, advanced lesions of apoE-/- mice. Methods & Results ApoE-/- mice on Western diet for 14 weeks developed advanced plaques, and were either sacrificed (“Baseline”), or continued on Western diet without or with F1394 and sacrificed after 14 more weeks. F1394 was not associated with systemic toxicity. Compared to the baseline group, lesion size progressed in both groups; however, F1394 significantly retarded plaque progression, and reduced plaque macrophage, free and esterified cholesterol, and tissue factor contents compared to the untreated group. Apoptosis of plaque cells was not increased, consistent with the decrease in lesional free cholesterol, plaque necrosis was not increased, and efferocytosis (phagocytic clearance of apoptotic cells) was not impaired. The effects of F1394 were independent of changes in plasma cholesterol levels. Conclusions Partial ACAT inhibition by F1394 lowered plaque cholesterol content and had other antiatherogenic effects in advanced lesions in apoE-/- mice without overt systemic or plaque toxicity, suggesting the continued potential of ACAT inhibition for the clinical treatment of atherosclerosis in spite of recent trial data. PMID:23139293

  20. PLACD-7T Study: Atherosclerotic Carotid Plaque Components Correlated with Cerebral Damage at 7 Tesla Magnetic Resonance Imaging.

    Science.gov (United States)

    den Hartog, A G; Bovens, S M; Koning, W; Hendrikse, J; Pasterkamp, G; Moll, F L; de Borst, G J

    2011-02-01

    In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero-Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk.

  1. Pregnancy associated plasma protein-A (PAPP-A) is not a marker of the vulnerable atherosclerotic plaque

    DEFF Research Database (Denmark)

    Iversen, Kasper; Teisner, Ane; Dalager, Soren

    2011-01-01

    To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A.......To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A....

  2. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARɣ and LXRα pathways

    Science.gov (United States)

    Chinetti-Gbaguidi, Giulia; Baron, Morgane; Bouhlel, Mohamed Amine; Vanhoutte, Jonathan; Copin, Corinne; Sebti, Yasmine; Derudas, Bruno; Mayi, Thérèse; Bories, Gael; Tailleux, Anne; Haulon, Stéphane; Zawadzki, Christophe; Jude, Brigitte; Staels, Bart

    2011-01-01

    Rationale A crucial step in atherogenesis is the infiltration of the sub-endothelial space of large arteries by monocytes where they differentiate into macrophages and transform into lipid-loaded foam cells. Macrophages are heterogeneous cells which adapt their response to environmental cytokines. Th1 cytokines promote monocyte differentiation into M1 macrophages, while Th2 cytokines trigger an “alternative” M2 phenotype. Objective We previously reported the presence of CD68+MR+ M2 macrophages in human atherosclerotic plaques. However, the function of these plaque CD68+MR+ macrophages is still unknown. Methods and Results Histological analysis revealed that CD68+MR+ locate far from the lipid core of the plaque and contain smaller lipid droplets compared to CD68+MR− macrophages. IL-4 polarized CD68+MR+ display a reduced capacity to handle and efflux cellular cholesterol due to low expression levels of the nuclear receptor Liver X Receptor (LXR)α and its target genes, ABCA1 and ApoE, caused by the high 15-lipoxygenase activity in CD68+MR+ macrophages. By contrast, CD68+MR+ highly express opsonins and receptors involved in phagocytosis resulting in high phagocytic activity. In M2 macrophages, Peroxisome Proliferator-Activated receptor (PPAR)γ activation enhances the phagocytic, but not the cholesterol trafficking pathways. Conclusions These data identify a distinct macrophage sub-population with a low susceptibility to become foam cells, but high phagocytic activity due to different regulatory activities of the PPARγ-LXRα pathways. PMID:21350215

  3. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARγ and LXRα pathways.

    Science.gov (United States)

    Chinetti-Gbaguidi, Giulia; Baron, Morgane; Bouhlel, Mohamed Amine; Vanhoutte, Jonathan; Copin, Corinne; Sebti, Yasmine; Derudas, Bruno; Mayi, Thérèse; Bories, Gael; Tailleux, Anne; Haulon, Stephane; Zawadzki, Christophe; Jude, Brigitte; Staels, Bart

    2011-04-15

    A crucial step in atherogenesis is the infiltration of the subendothelial space of large arteries by monocytes where they differentiate into macrophages and transform into lipid-loaded foam cells. Macrophages are heterogeneous cells that adapt their response to environmental cytokines. Th1 cytokines promote monocyte differentiation into M1 macrophages, whereas Th2 cytokines trigger an "alternative" M2 phenotype. We previously reported the presence of CD68(+) mannose receptor (MR)(+) M2 macrophages in human atherosclerotic plaques. However, the function of these plaque CD68(+)MR(+) macrophages is still unknown. Histological analysis revealed that CD68(+)MR(+) macrophages locate far from the lipid core of the plaque and contain smaller lipid droplets compared to CD68(+)MR(-) macrophages. Interleukin (IL)-4-polarized CD68(+)MR(+) macrophages display a reduced capacity to handle and efflux cellular cholesterol because of low expression levels of the nuclear receptor liver x receptor (LXR)α and its target genes, ABCA1 and apolipoprotein E, attributable to the high 15-lipoxygenase activity in CD68(+)MR(+) macrophages. By contrast, CD68(+)MR(+) macrophages highly express opsonins and receptors involved in phagocytosis, resulting in high phagocytic activity. In M2 macrophages, peroxisome proliferator-activated receptor (PPAR)γ activation enhances the phagocytic but not the cholesterol trafficking pathways. These data identify a distinct macrophage subpopulation with a low susceptibility to become foam cells but high phagocytic activity resulting from different regulatory activities of the PPARγ-LXRα pathways.

  4. A Critical Role for Extracellular DNA in Dental Plaque Formation.

    Science.gov (United States)

    Rostami, N; Shields, R C; Yassin, S A; Hawkins, A R; Bowen, L; Luo, T L; Rickard, A H; Holliday, R; Preshaw, P M; Jakubovics, N S

    2017-02-01

    Extracellular DNA (eDNA) has been identified in the matrix of many different monospecies biofilms in vitro, including some of those produced by oral bacteria. In many cases, eDNA stabilizes the structure of monospecies biofilms. Here, the authors aimed to determine whether eDNA is an important component of natural, mixed-species oral biofilms, such as plaque on natural teeth or dental implants. To visualize eDNA in oral biofilms, approaches for fluorescently stained eDNA with either anti-DNA antibodies or an ultrasensitive cell-impermeant dye, YOYO-1, were first developed using Enterococcus faecalis, an organism that has previously been shown to produce extensive eDNA structures within biofilms. Oral biofilms were modelled as in vitro "microcosms" on glass coverslips inoculated with the natural microbial population of human saliva and cultured statically in artificial saliva medium. Using antibodies and YOYO-1, eDNA was found to be distributed throughout microcosm biofilms, and was particularly abundant in the immediate vicinity of cells. Similar arrangements of eDNA were detected in biofilms on crowns and overdenture abutments of dental implants that had been recovered from patients during the restorative phase of treatment, and in subgingival dental plaque of periodontitis patients, indicating that eDNA is a common component of natural oral biofilms. In model oral biofilms, treatment with a DNA-degrading enzyme, NucB from Bacillus licheniformis, strongly inhibited the accumulation of biofilms. The bacterial species diversity was significantly reduced by treatment with NucB and particularly strong reductions were observed in the abundance of anaerobic, proteolytic bacteria such as Peptostreptococcus, Porphyromonas and Prevotella. Preformed biofilms were not significantly reduced by NucB treatment, indicating that eDNA is more important or more exposed during the early stages of biofilm formation. Overall, these data demonstrate that dental plaque eDNA is

  5. TU-F-12A-06: BEST IN PHYSICS (IMAGING) - A Novel Catheter-Based Radionuclide Imaging System to Characterize Atherosclerotic Plaque

    Energy Technology Data Exchange (ETDEWEB)

    Zaman, R; Kosuge, H; Carpenter, C; Pratx, G; Sun, C; McConnell, M; Xing, L [Stanford University School of Medicine, Stanford, CA (United States)

    2014-06-15

    Purpose: Atherosclerosis underlies coronary artery diseases, the leading cause of death in the United States and worldwide. In this study, we developed a novel catheter-based radionuclide imaging (CRI) system to image 18F-fluorodeoxyglucose (18F-FDG), a radionuclide, a marker of vascular inflammation, in murine carotid arteries and characterized the system for spatial resolution from multiple scintillating materials. Methods: The catheter system includes 35 mm and 8 mm fixed focal length lenses, which are subsequently connected to a CMOS camera and fiber holder. The distal ferrule of an image bundle is terminated with a wide-angle lens. The novelty of this system is a scintillating balloon with a crystal tip in the front of the wide angle lens to image light from the decay of 18F-FDG emission signal. The scintillating balloon is fabricated from 1mL of silicone RTV catalyst mixed with 1 mL base and 50 mg/mL calcium fluoride doped with Europium (CaF2:Eu). To identify the optimal scintillating materials with respect to resolution, we calculated modulation transfer function (MTF) of Yttrium Aluminum Garnet doped with Cerium (YAG:Ce), anthracene, and CaF2:Eu phosphors using a thin line optical phantom (Fig. 1a-1b). Macrophage-rich FVB murine atherosclerotic carotid plaque model (n = 4) was used in ex vivo experiments. Confirmatory imaging was also performed by an external optical imaging system (IVIS-200). Results: Analysis of the different phosphors (Fig 1b) showed that CaF2:Eu enabled the best resolution of 1.2μm. The CRI system visualized 18F-FDG in atherosclerotic plaques (Fig. 1d). The ligated left carotid (LR) artery exhibited 4× higher 18F-FDG signal intensity compared to the non-ligated right carotid (negative control) artery (1.65×10{sup 2} ±4.07×10{sup 1} vs. 4.44×10{sup 1}±2.17×10{sup 0}, A.U., p = 0.005) and confirmed with IVIS-200 (Fig. 1d). Conclusion: This CRI system enables high-resolution and sensitive detection of 18F-FDG uptake by murine

  6. The prolactin receptor is expressed in macrophages within human carotid atherosclerotic plaques: a role for prolactin in atherogenesis?

    NARCIS (Netherlands)

    Reuwer, Anne; van Eijk, Marco; Houttuijn-Bloemendaal, Felicia; van der Loos, Chris; Claessen, Nike; Teeling, Peter; Kastelein, J. J.; Hamann, Jörg; Goffin, Vincent; von der Thüsen, Jan; Twickler, Marcel; Aten, Jan

    2011-01-01

    Atherosclerotic vascular disease is the consequence of a chronic inflammatory process, and prolactin has been shown to be a component of the inflammatory response. Additionally, recent studies indicate that prolactin contributes to an atherogenic phenotype. We hypothesized that this may be the

  7. The origins of urinary stone disease: upstream mineral formations initiate downstream Randall's plaque

    National Research Council Canada - National Science Library

    Hsi, Ryan S; Ramaswamy, Krishna; Ho, Sunita P; Stoller, Marshall L

    2017-01-01

    .... A biomechanical perspective on Randall's plaque formation through form and function relationships is applied to functional units within the kidney, we have termed the 'medullo-papillary complex...

  8. Intra-Arterial Drug and Light Delivery for Photodynamic Therapy Using Visudyne?: Implication for Atherosclerotic Plaque Treatment

    OpenAIRE

    Jain, Manish; Zellweger, Matthieu; Frobert, Aurélien; Valentin, Jérémy; Bergh, Hubert van den; Wagnières, Georges; Cook, Stéphane; Giraud, Marie-Noelle

    2016-01-01

    Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus, this “intra-arterial” PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. Aim: ...

  9. Intra-arterial drug and light delivery for photodynamic therapy using Visudyne®: implication for atherosclerotic plaque treatment

    OpenAIRE

    Manish Jain; Matthieu Zellweger; Aurélien Frobert; Jérémy Valentin; Hubert van den Bergh; Georges Wagnières; Stéphane Cook; Marie-Noelle Giraud

    2016-01-01

    Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus this intra-arterial PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. Aim: We cha...

  10. Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice.

    Science.gov (United States)

    Srivastava, Sanjay; Vladykovskaya, Elena N; Haberzettl, Petra; Sithu, Srinivas D; D'Souza, Stanley E; States, J Christopher

    2009-11-15

    Exposure to arsenic-contaminated water has been shown to be associated with cardiovascular disease, especially atherosclerosis. We examined the effect of arsenic exposure on atherosclerotic lesion formation, lesion composition and nature in ApoE-/- mice. Early post-natal exposure (3-week-old mice exposed to 49 ppm arsenic as NaAsO(2) in drinking water for 7 weeks) increased the atherosclerotic lesion formation by 3- to 5-fold in the aortic valve and the aortic arch, without affecting plasma cholesterol. Exposure to arsenic for 13 weeks (3-week-old mice exposed to 1, 4.9 and 49 ppm arsenic as NaAsO(2) in drinking water) increased the lesion formation and macrophage accumulation in a dose-dependent manner. Temporal studies showed that continuous arsenic exposure significantly exacerbated the lesion formation throughout the aortic tree at 16 and 36 weeks of age. Withdrawal of arsenic for 12 weeks after an initial exposure for 21 weeks (to 3-week-old mice) significantly decreased lesion formation as compared with mice continuously exposed to arsenic. Similarly, adult exposure to 49 ppm arsenic for 24 weeks, starting at 12 weeks of age increased lesion formation by 2- to 3.6-fold in the aortic valve, the aortic arch and the abdominal aorta. Lesions of arsenic-exposed mice displayed a 1.8-fold increase in macrophage accumulation whereas smooth muscle cell and T-lymphocyte contents were not changed. Expression of pro-inflammatory chemokine MCP-1 and cytokine IL-6 and markers of oxidative stress, protein-HNE and protein-MDA adducts were markedly increased in lesions of arsenic-exposed mice. Plasma concentrations of MCP-1, IL-6 and MDA were also significantly elevated in arsenic-exposed mice. These data suggest that arsenic exposure increases oxidative stress, inflammation and atherosclerotic lesion formation.

  11. {sup 99m}Tc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Annovazzi, Alessio; D' Alessandria, Calogero; Scopinaro, Francesco [University La Sapienza, Nuclear Medicine, 2nd Faculty of Medicine, Rome (Italy); Bonanno, Elena; Spagnoli, Luigi G. [University Tor Vergata, Department of Biopathology and Diagnostic Imaging, Rome (Italy); Arca, Marcello [University La Sapienza, Department of Clinical and Applied Medical Therapy, 1st Faculty of Medicine, Rome (Italy); Marcoccia, Antonella; Violi, Francesco [University La Sapienza, Medical Clinical Institute 1, 1st Faculty of Medicine, Rome (Italy); Toma, Giorgio De [University La Sapienza, Department of Surgery Pietro Valdoni, 1st Faculty of Medicine, Rome (Italy); Signore, Alberto [University La Sapienza, Nuclear Medicine, 2nd Faculty of Medicine, Rome (Italy); University of Groningen, Department of Nuclear Medicine, Groningen (Netherlands); Ospedale S. Andrea, Nuclear Medicine, Roma (Italy)

    2006-02-01

    Several histopathological studies have demonstrated that vulnerable plaques are enriched in inflammatory cells. The aims of this study were: (1a) to test the ability of {sup 99m}Tc-labelled interleukin-2 ({sup 99m}Tc-IL2) to bind to IL2R-positive (IL2R+) cells in carotid plaques and (1b) to correlate the plaque uptake of {sup 99m}Tc-IL2, measured in vivo, with the number of IL2R+ cells within the plaque, measured ex vivo by histology (transversal study, TS), and (2) to evaluate changes in {sup 99m}Tc-IL2 uptake in plaques, before and after treatment with a statin or a hypocholesterolaemic diet (longitudinal study, LS). Ultrasound scan was performed for plaque characterisation and localisation. Fourteen patients (16 plaques) eligible for endoarterectomy were recruited for the TS and underwent {sup 99m}Tc-IL2 scintigraphy before surgery. Nine patients (13 plaques) were recruited for the LS; these patients received atorvastatin or a standard hypocholesterolaemic diet and {sup 99m}Tc-IL2 scintigraphy was performed before and after 3 months of treatment. The degree of {sup 99m}Tc-IL2 uptake was expressed as the plaque/background (T/B) ratio. In patients from TS, T/B ratios correlated with the percentage of IL2R+ cells at histology (r=0.707; p=0.002) and the number of IL2R+ cells at flow cytometry (r=0.711; p=0.006). No correlations were observed between ultrasound scores and either scintigraphic or histological findings. In patients from the LS, the mean {sup 99m}Tc-IL2 uptake decreased in statin-treated patients (1.75{+-}0.50 vs 2.16{+-}0.44; p=0.012), while it was unchanged in the patients on the hypocholesterolaemic diet (2.33{+-}0.45 vs 2.34{+-}0.5). {sup 99m}Tc-IL2 accumulates in vulnerable carotid plaques; this accumulation is correlated with the amount of IL2R+ cells and is influenced by lipid-lowering treatment with a statin. (orig.)

  12. Distribution of selected elements in atherosclerotic plaques of apoE/LDLR-double knockout mice subjected to dietary and pharmacological treatments

    Energy Technology Data Exchange (ETDEWEB)

    Gajda, Mariusz, E-mail: mmgajda@cyf-kr.edu.pl [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Kowalska, Joanna [Institute of Nuclear Physics, Radzikowskiego 152, 31-342 Krakow (Poland); Banas, Agnieszka; Banas, Krzysztof [Singapore Synchrotron Light Source, National University of Singapore, 5 Research Link, 117603 Singapore (Singapore); Kwiatek, Wojciech M. [Institute of Nuclear Physics, Radzikowskiego 152, 31-342 Krakow (Poland); Kostogrys, Renata B. [Department of Human Nutrition, Agricultural University of Krakow, Balicka 122, 30-149, Krakow (Poland); Mateuszuk, Lukasz; ChLopicki, Stefan [Department of Experimental Pharmacology, Jagiellonian University Medical College, Kopernika 7, 31-531 Krakow (Poland); Litwin, Jan A. [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Appel, Karen [Hasylab, DESY, Notkestrasse 85, D-22607, Hamburg (Germany)

    2011-10-15

    Gene-targeted, apolipoprotein E and LDL receptor-double knockout (apoE/LDLR{sup -/-}) mice represent a new animal model that displays severe hyperlipidemia and atherosclerosis. The aim of the present study was to show changes in histomorphology and in distribution of selected elements in atherosclerotic plaques of apoE/LDLR{sup -/-} mice fed egg-rich proatherosclerotic diet (5% egg-yolk lyophilisate) supplemented or not with perindopril (inhibitor of angiotensin converting enzyme; 2 mg/kg b.w.). Synchrotron radiation micro-X-ray fluorescence spectrometry was combined with histological stainings to determine distribution and concentration of trace and essential elements in atherosclerotic lesions. More advanced atherosclerotic lesions expressed by total area occupied by lipids (oil red-O staining) and by macrophages (CD68 immunohistochemistry) were observed in animals fed egg-rich diet. The perindopril treatment attenuated these effects. No significant differences were observed in the number of intimal smooth muscle cells (smooth muscle actin immunohistochemistry). In animals fed egg-rich diet significantly higher concentrations of Ca and significantly lower contents of S, Cl, , Fe, Cu, Zn and Se in atheromas were seen in comparison to chow diet-fed animals. After pharmacological treatment, concentrations of S, Cl, Fe, Cu, Zn and Se showed the tendency to achieve levels like in animals fed normal diet. K level differed only in group treated with perindopril. Concentration of P did not significantly vary in all experimental groups. Perindopril showed its potency to reduce atherosclerosis, as estimated by the size of the atheroma and content of pro- and antiatherogenic elements.

  13. Grating-based X-ray phase-contrast tomography of atherosclerotic plaque at high photon energies.

    Science.gov (United States)

    Hetterich, Holger; Fill, Sandra; Herzen, Julia; Willner, Marian; Zanette, Irene; Weitkamp, Timm; Rack, Alexander; Schüller, Ulrich; Sadeghi, Mojtaba; Brandl, Richard; Adam-Neumair, Silvia; Reiser, Maximilian; Pfeiffer, Franz; Bamberg, Fabian; Saam, Tobias

    2013-09-01

    Tissue characterization of atherosclerosis by absorption-based imaging methods is limited due to low soft-tissue contrast. Grating-based phase-contrast computed tomography (PC-CT) may become an alternative for plaque assessment if the phase signal can be retrieved at clinically applicable photon energies. The aims of this feasibility study were (i) to characterize arterial vessels at low and high photon energies, (ii) to extract qualitative features and (iii) quantitative phase-contrast Hounsfield units (HU-phase) of plaque components at 53 keV using histopathology as gold standard. Five human carotid artery specimens underwent grating-based PC-CT using synchrotron radiation of either 23 keV or 53 keV and histological work-up. Specimens without advanced atherosclerosis were used to extract signal criteria of vessel layers. Diseased specimens were screened for important plaque components including fibrous tissue (FT), lipid (LIP), necrotic core (NEC), intraplaque hemorrhage (IPH), inflammatory cell infiltration (INF) and calcifications (CA). Qualitative features as well as quantitative HU-phase were analyzed. Thirty-three regions in 6 corresponding PC-CT scans and histology sections were identified. Healthy samples had the same signal characteristics at 23 keV and 53 keV with bright tunica intima and adventitia and dark media. Plaque components showed differences in signal intensity and texture at 53 keV. Quantitative analysis demonstrated the highest HU-phase of soft plaque in dense FT. Less organized LIP, NEC and INF were associated with lower HU-phase values. The highest HU-phase were measured in CA. PC-CT of atherosclerosis is feasible at high, clinically relevant photon energies and provides detailed information about plaque structure including features of high risk vulnerable plaques. Copyright © 2013. Published by Elsevier GmbH.

  14. The effect of lipid regulation with atorvastatin on the blood lipid levels and carotid artery plaques in patients with atherosclerotic cerebral infarction

    Directory of Open Access Journals (Sweden)

    Shu XU

    2015-11-01

    Full Text Available Objective To analyze the effect of intensive lipid regulation treatment with atorvastatin on the blood lipid levels and carotid artery plaques in patients with atherosclerotic cerebral infarction.  Methods Ninety-two patients with atherosclerotic cerebral infarction were randomly divided into two groups: observation group (treated by atorvastatin calcium with the dosage of 20 mg/d, N = 46 and control group (treated by diet without lipid-rich food, N=46. Besides, other drugs given to the patients in two groups were the same. The blood lipid levels and the changes of carotid artery plaques in two groups were analyzed and compared before treatment and 3 months after treatment. Results After treatment, the concentrations of total cholesterol [TC, (4.23 ± 0.92 mmol/L vs (5.24 ± 0.68 mmol/L], triglyceride [TG, (2.46 ± 0.28 mmol/L vs (3.33 ± 0.47 mmol/L], low-density lipoprotein cholesterol [LDL-C, (2.52 ± 0.38 mmol/L vs (4.78 ± 0.86 mmol/L] in the patients of observation group were all decreased and significantly lower than those in the control group (P = 0.000, for all, and the concentration of high-density lipoprotein cholesterol [HDL-C, (1.13 ± 0.41 mmol/L vs (0.85 ± 0.32 mmol/L] in the patients of observation group was increased and significantly than that in the control group (P = 0.003. The carotid artery plaque size [(20.25 ± 0.32 mm2 vs (24.42 ± 10.33 mm2] and thickness [(0.59 ± 0.13 mm vs (1.93 ± 0.23 mm] of carotid artery plaques and intima?media thickness [IMT, (1.32 ± 0.67 mm vs (1.63 ± 0.56 mm] of common carotid artery (CCA in the patients of observation group were all significantly lower than those in patients in the control group (P = 0.000, 0.000, 0.010, respectively. Comparing serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, creatine kinase (CK and creatinine (Cr levels after treatment with before treatment, there was no significant difference between 2 groups (P > 0.05, for all.  Conclusions

  15. Regression and shift in composition of coronary atherosclerotic plaques by pioglitazone: insight from an intravascular ultrasound analysis.

    Science.gov (United States)

    Clementi, Fabrizio; Di Luozzo, Marco; Mango, Ruggiero; Luciani, Giulio; Trivisonno, Antonio; Pizzuto, Francesco; Martuscelli, Eugenio; Mehta, Jawahar L; Romeo, Francesco

    2009-03-01

    Plaque reduction with the use of pioglitazone and statin combination therapy has been observed in carotid plaque. We sought to investigate the effect of combination therapy with statins and pioglitazone on coronary plaque regression and composition with the use of intravascular ultrasound (IVUS) and intravascular ultrasound-virtual histology (IVUS-VH). We analysed 29 plaques in 25 diabetic patients with angiographic evidence of nonsignificant coronary lesions with IVUS-VH. Patients were treated with 80 mg of atorvastatin and 30 mg of pioglitazone daily for 6 months. After 6 months of therapy, IVUS-VH of each lesion was reacquired. Mean elastic external membrane volume was significantly reduced between baseline and follow-up (343.9 vs. 320.5 mm; P < 0.05) as was mean total atheroma volume (179.3 vs. 166.6 mm; P < 0.05). Change in total atheroma volume showed a 6.3% mean reduction. Areas of fibrous tissue, fibrolipidic tissue and calcium decreased over the 6 months of follow-up, although not significantly. On the other hand, the necrotic core increased from 9 to 14% (P < 0.05). Our data demonstrated that atorvastatin/pioglitazone association is able to induce significant regression of coronary atherosclerosis, acting on plaque composition. Our findings are preliminary results and will be confirmed in an ongoing randomized placebo-controlled multicenter trial (PIPER; Pioglitazone for Prevention of Restenosis in Diabetics with Complex Lesion; trial registration: clinical trials.gov. Identifier: NCT 00376870).

  16. Assessment of atherosclerotic plaque collagen content and architecture using polarization-sensitive optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Doradla, Pallavi; Villiger, Martin; Tshikudi, Diane M.; Bouma, Brett E.; Nadkarni, Seemantini K.

    2016-02-01

    Acute myocardial infarction, caused by the rupture of vulnerable coronary plaques, is the leading cause of death worldwide. Collagen is the primary extracellular matrix macromolecule that imparts the mechanical stability to a plaque and its reduction causes plaque instability. Intracoronary polarization sensitive optical coherence tomography (PS-OCT) measures the polarization states of the backscattered light from the tissue to evaluate plaque birefringence, a material property that is elevated in proteins such as collagen with an ordered structure. Here we investigate the dependence of the PS-OCT parameters on the quantity of the plaque collagen and fiber architecture. In this study, coronary arterial segments from human cadaveric hearts were evaluated with intracoronary PS-OCT and compared with Histopathological assessment of collagen content and architecture from picrosirius-red (PSR) stained sections. PSR sections were visualized with circularly-polarized light microscopy to quantify collagen birefringence, and the additional assessment of color hue indicated fibril thickness. Due to the ordered architecture of thick collagen fibers, a positive correlation between PS-OCT retardation and quantity of thick collagen fibers (r=0.54, p=0.04), and similarly with the total collagen content (r=0.51, p=0.03) was observed. In contrast, there was no perceivable relationship between PS-OCT retardation and the presence of thin collagen fibers (r=0.08, p=0.07), suggesting that thin and disorganized collagen fiber architecture did not significantly contribute to the PS-OCT retardation. Further analysis will be performed to assess the relationship between PS-OCT retardation and collagen architecture based on immunohistochemical analysis of collagen type. These results suggest that intracoronary PS-OCT may open the opportunity to assess collagen architecture in addition total collagen content, potentially enabling an improved understanding of coronary plaque rupture.

  17. HMGB1 is associated with atherosclerotic plaque composition and burden in patients with stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Martin Andrassy

    Full Text Available OBJECTIVES: The role of inflammation in atherosclerosis is widely appreciated. High mobility group box 1 (HMGB1, an injury-associated molecular pattern molecule acting as a mediator of inflammation, has recently been implicated in the development of atherosclerosis. In this study, we sought to investigate the association of plasma HMGB1 with coronary plaque composition in patients with suspected or known coronary artery disease (CAD. DESIGN: HMGB1, high sensitive troponin T (hsTnT and high sensitive C-reactive protein (hsCRP were determined in 152 consecutive patients with suspected or known stable CAD who underwent clinically indicated 256-slice coronary computed tomography angiography (CCTA. Using CCTA, we assessed 1 coronary calcification, 2 non-calcified plaque burden and 3 the presence of vascular remodeling in areas of non-calcified plaques. RESULTS: Using univariate analysis, hsCRP, hsTnT and HMGB1 as well as age, and atherogenic risk factors were associated with non-calcified plaque burden (r = 0.21, p = 0.009; r = 0.48, p<0.001 and r = 0.34, p<0.001, respectively. By multivariate analysis, hsTnT and HMGB1 remained independent predictors of the non-calcified plaque burden (r = 0.48, p<0.01 and r = 0.34, p<0.001, respectively, whereas a non-significant trend was noticed for hs-CRP (r = 0.21, p = 0.07. By combining hsTnT and HMGB1, a high positive predictive value for the presence of non-calcified and remodeled plaque (96% and 77%, respectively was noted in patients within the upper tertiles for both biomarkers, which surpassed the positive predictive value of each marker separately. CONCLUSIONS: In addition to hs-TnT, a well-established cardiovascular risk marker, HMGB1 is independently associated with non-calcified plaque burden in patients with stable CAD, while the predictive value of hs-CRP is lower. Complementary value was observed for hs-TnT and HMGB1 for the prediction of complex coronary plaque.

  18. Familial influence on plaque formation in the beagle brain.

    Science.gov (United States)

    Russell, M J; White, R; Patel, E; Markesbery, W R; Watson, C R; Geddes, J W

    1992-12-01

    Aged canines exhibit central neuropathological changes strikingly similar to those seen in patients with Alzheimer's disease. In this study, brain tissue from pure bred beagles raised in a controlled environment were examined for Alzheimer-like pathology. The mean age of the animals was 15.6 years. The incidence of plaques among these 29 dogs was 65.5%. Of the 19 samples that demonstrated Alzheimer-like pathology, 18 were characterized as diffuse and one as neuritic. Plaque density was found to be independent of age. Plaque numbers were highest in the perirhinal cortex and the adjacent temporal cortex. Familial influence on plaque development is supported by congruence within 15 of the 16 litters examined (p < 0.001). In this environmentally controlled group the diffuse plaques were rarely converted to the dense neuritic plaques found in Alzheimer's disease.

  19. Semiquantitative analysis of atherosclerotic plaque using optical coherence tomography and time-of-flight secondary ion mass spectrometry

    Science.gov (United States)

    Korol, Renee M.; Togonu-Bickersteth, Babajide; Yang, Victor X.; Dimov, Stamen; Vatsya, Pracha; Gordon, Maggie; Vitkin, Alex; Liu, Liying; Canham, Peter; Clarke, Sharon; Lucas, Alexandra

    2003-10-01

    Atherosclerosis is the underlying vascular pathology that initiates arterial thromboembolic occlusions (myocardial infarctions, strokes and peripheral vessel blockage). Two imaging modalities, Optical Coherence Tomography (OCT) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), were investigated for detection and compositional analysis of unstable plaque associated with plaque erosion and sudden occlusion. OCT produces high resolution images whereas mass spectrometry images provide information on the spatial distribution of chemical elements. Diseased carotid arteries taken from patients with high-risk lesions were imaged with OCT and ToF-SIMS to give molecular and metabolic information, and matched with histopathology. OCT results show clear indications of vascular remodeling by the presence of fatty acid deposits, fibrous tissue and calcifications. ToF-SIMS further characterized changes based on secondary ion topography analysis where a high 23Na/39K ratio was indicative of arterial tissue degradation and the amount of 40Ca corresponded with late stage atherosclerosis. This pilot experiment has demonstrated that in vitro OCT imaging and ToF-SIMS of diseased carotid arteries have scientific merit for targeting clinically relevant morphology and metabolic changes to compare stable and unstable plaque. These optical techniques provide complimentary metabolic and molecular information on unstable plaque, specifically cell break-down with altered ion ratios of 23Na, 39K and 40Ca.

  20. The role of contrast-enhanced ultrasound (CEUS) in visualizing atherosclerotic carotid plaque vulnerability: Which injection protocol? Which scanning technique?

    Energy Technology Data Exchange (ETDEWEB)

    Iezzi, Roberto, E-mail: roberto.iezzi@rm.unicatt.it [Department of Bioimaging and Radiological Sciences, Institute of Radiology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Petrone, Gianluigi [Institute of Pathology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168, Rome (Italy); Ferrante, Angela [Department of Vascular Surgery, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Lauriola, Libero [Institute of Pathology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168, Rome (Italy); Vincenzoni, Claudio [Department of Vascular Surgery, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Torre, Michele Fabio la [Department of Bioimaging and Radiological Sciences, Institute of Radiology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Snider, Francesco [Department of Vascular Surgery, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Rindi, Guido [Institute of Pathology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168, Rome (Italy); Bonomo, Lorenzo [Department of Bioimaging and Radiological Sciences, Institute of Radiology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy)

    2015-05-15

    Highlights: • CEUS is a safe and efficacious technique for the identification and characterization of carotid plaque. • CEUS represents a diagnostic tool for the management of patients with carotid plaque, particularly in asymptomatic patients. • Improved diagnostic performance is achieved with the injection of 4 mL bolus of contrast-medium. • Improved diagnostic performance is achieved with the use of Dynamic Imaging rather than late-phase imaging. - Abstract: Purpose: To correlate the degree of plaque vulnerability as determined by contrast-enhanced ultrasound (CEUS) with histological findings. Secondary objectives were to optimize the CEUS acquisition technique and image evaluation methods. Materials and methods: Fifty consecutive patients, either symptomatic and asymptomatic referring to our department in order to perform carotid endarterectomy (TEA), were enrolled. Each patient provided informed consent before undergoing CEUS. Ultrasound examination was performed using high-frequency (8–14 MHz) linear probe and a non-linear pulse inversion technique (mechanical index: 0.09–1.3). A double contrast media injection (Sonovue, 2 mL and 4 mL; Bracco, Italy) was performed. Two videotapes were recorded for every injection: early “dynamic” phase and late “flash” phase, performed with 6 high mechanical index impulses. Movies were quantitatively and qualitatively evaluated. Qualitative and quantitative evaluation were statistically compared to immunohistological diagnosis of vulnerable plaque, considered as gold standard. Results: Qualitative CEUS evaluation obtained high statistical results when compared to immunohistological results, with values of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of 94%, 68%, 87%, 85% and 86%, respectively, which became higher if considering only asymptomatic patient, with a NPV of 91%. Nevertheless, quantitative software evaluation proved less

  1. [Role of syndecan-2 in amyloid plaque formation].

    Science.gov (United States)

    Leonova, E I; Galzitskaia, O V

    2015-01-01

    The famous phrase of F. Engels "Life is the mode of existence of protein bodies", has deeply insinuated itself in our mind. However at a more profound insight, the form of protein bodies is associaited not only with the fact of their existence, but also with the time changes. What unites all of us in our oldage? The answer is clear: it is the change in the way of existence of protein molecules, and more precisely, their uncontrolled aggregation that can take place in any organ and be associated with any protein. In spite of different clinical presentations, all diseases associated with pathological accumulation of aggregated proteins are combined in a general group called amyloisosis. Depen- dent on the place of formation, it is possible to distinguish an infinite number of pathologies from neurodegen- erative and oncologic ones to arthritis and tuberculosis. There is no doubt that provided all clandestine mechanisms are clarified at which an absolutely normal functioning.protein can transform into a pathological aggregated form, it will give us a chance to prevent protein aggregation and create a new form of drugs for prolongation of life. In this review we considered the function of syndecan-2, the structure of syndecan-2 and its role in the formation of amyloid plaques.

  2. The role of contrast-enhanced ultrasound (CEUS) in visualizing atherosclerotic carotid plaque vulnerability: which injection protocol? Which scanning technique?

    Science.gov (United States)

    Iezzi, Roberto; Petrone, Gianluigi; Ferrante, Angela; Lauriola, Libero; Vincenzoni, Claudio; la Torre, Michele Fabio; Snider, Francesco; Rindi, Guido; Bonomo, Lorenzo

    2015-05-01

    To correlate the degree of plaque vulnerability as determined by contrast-enhanced ultrasound (CEUS) with histological findings. Secondary objectives were to optimize the CEUS acquisition technique and image evaluation methods. Fifty consecutive patients, either symptomatic and asymptomatic referring to our department in order to perform carotid endarterectomy (TEA), were enrolled. Each patient provided informed consent before undergoing CEUS. Ultrasound examination was performed using high-frequency (8-14 MHz) linear probe and a non-linear pulse inversion technique (mechanical index: 0.09-1.3). A double contrast media injection (Sonovue, 2 mL and 4 mL; Bracco, Italy) was performed. Two videotapes were recorded for every injection: early "dynamic" phase and late "flash" phase, performed with 6 high mechanical index impulses. Movies were quantitatively and qualitatively evaluated. Qualitative and quantitative evaluation were statistically compared to immunohistological diagnosis of vulnerable plaque, considered as gold standard. Qualitative CEUS evaluation obtained high statistical results when compared to immunohistological results, with values of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of 94%, 68%, 87%, 85% and 86%, respectively, which became higher if considering only asymptomatic patient, with a NPV of 91%. Nevertheless, quantitative software evaluation proved less effective and could not reach similar results. Carotid plaque enhancement assessed with CEUS well correlates with histological assessment of plaque instability. CEUS may provide valuable information for plaque risk stratification and may play a role in the indication to treatment of patients with carotid stenoses, particularly in asymptomatic population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Maintenance of Macrophage Redox Status by ChREBP Limits Inflammation and Apoptosis and Protects against Advanced Atherosclerotic Lesion Formation

    Directory of Open Access Journals (Sweden)

    Vincent Sarrazy

    2015-10-01

    Full Text Available Enhanced glucose utilization can be visualized in atherosclerotic lesions and may reflect a high glycolytic rate in lesional macrophages, but its causative role in plaque progression remains unclear. We observe that the activity of the carbohydrate-responsive element binding protein ChREBP is rapidly downregulated upon TLR4 activation in macrophages. ChREBP inactivation refocuses cellular metabolism to a high redox state favoring enhanced inflammatory responses after TLR4 activation and increased cell death after TLR4 activation or oxidized LDL loading. Targeted deletion of ChREBP in bone marrow cells resulted in accelerated atherosclerosis progression in Ldlr−/− mice with increased monocytosis, lesional macrophage accumulation, and plaque necrosis. Thus, ChREBP-dependent macrophage metabolic reprogramming hinders plaque progression and establishes a causative role for leukocyte glucose metabolism in atherosclerosis.

  4. Quantitative analysis of ultrasound B-mode images of carotid atherosclerotic plaque: correlation with visual classification and histological examination

    DEFF Research Database (Denmark)

    Wilhjelm, Jens E.; Grønholdt, Marie-Louise; Wiebe, Brit

    1998-01-01

    This paper presents a quantitative comparison of three types of information available for 52 patients scheduled for carotid endarterectomy: subjective classification of the ultrasound images obtained during scanning before operation, first- and second-order statistical features extracted from...... regions of the plaque in still ultrasound images from three orthogonal scan planes and finally a histological analysis of the surgically removed plaque. The quantitative comparison was made with the linear model and with separation of the available data into training and test sets. The comparison...... of subjective classification with features from still ultrasound images revealed an overall agreement of 60 % for classification of echogenicity and 70 % for classification of structure. Comparison of the histologically determined relative volume of soft materials with features from the still images revealed...

  5. 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.

  6. Plaque formation and lactic acid production after use of amine fluoride/stannous fluoride mouthrinse

    NARCIS (Netherlands)

    Gerardu, V.A.M.; Buijs, M.; Loveren, C. van; Cate, J.M. ten

    2007-01-01

    The aim of this study was lo determine the effects of 3 wk of daily rinsing with amine fluoride/stannous fluoride (AmF/SnF2) mouthrinse on plaque formation at buccal and interproximal sites, and on the acid production in plaque. in a randomized clinical trial with 30 participants. The amount of

  7. 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

    endothelial growth factor (VEGF) and integrin aV and integrin ß3 subunits, genes essential during neoangiogenesis. We also evaluated the gene expression of CD34, a measure of microvessel density (MVD), as well as CD68, MMP-9, and cathepsin K, genes of major importance in plaque vulnerability. Gene expression...... 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...

  8. 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

    inhibitor. Immunofluorescent tissue analysis after TLR7 stimulation showed IL-10 expression in T cells, macrophages and vascular smooth muscle cells. TLR7 mRNA levels in the plaques were correlated with IL-10 receptor (r=0.4031, p....This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re...

  9. Effect of AVE 0991 angiotensin-(1-7) receptor agonist treatment on elemental and biomolecular content and distribution in atherosclerotic plaques of apoE-knockout mice

    Science.gov (United States)

    Kowalska, J.; Gajda, M.; Jawień, J.; Kwiatek, W. M.; Appel, K.; Dumas, P.

    2013-12-01

    Gene-targeted apolipoprotein E-knockout (apoE-KO) mice display early and highly progressive vascular lesions containing lipid deposits and they became a reliable animal model to study atherosclerosis. The aim of the present study was to investigate the effect of AVE 0991 angiotensin-(1-7) receptor agonist on the distribution of selected pro- and anti- inflammatory elements as well as biomolecules in atherosclerotic plaques of apoE-knockout mice. Synchrotron radiation-based X-ray fluorescence (micro-XRF) and Fourier Transform Infrared (micro-FTIR) microspectroscopies were applied. Two-month-old apoE-KO mice were fed for following four months diet supplemented with AVE 0991 (0.58 μmol/kg b.w. per day). Histological sections of ascending aortas were analyzed spectroscopically. The distribution of P, Ca, Fe and Zn were found to correspond with histological structure of the lesion. Significantly lower contents of P, Ca, Zn and significantly higher content of Fe were observed in animals treated with AVE 0991. Biomolecular analysis showed lower lipids saturation level and lower lipid to protein ratio in AVE 0991 treated group. Protein secondary structure was studied according to the composition of amide I band (1660 cm-1) and it demonstrated higher proportion of β-sheet structure as compared to α-helix in both studied groups.

  10. Influence of material property variability on the mechanical behaviour of carotid atherosclerotic plaques: a 3D fluid-structure interaction analysis.

    Science.gov (United States)

    Yuan, Jianmin; Teng, Zhongzhao; Feng, Jiaxuan; Zhang, Yongxue; Brown, Adam J; Gillard, Jonathan H; Jing, Zaiping; Lu, Qingsheng

    2015-08-01

    Mechanical analysis has been shown to be complementary to luminal stenosis in assessing atherosclerotic plaque vulnerability. However, patient-specific material properties are not available and the effect of material properties variability has not been fully quantified. Media and fibrous cap (FC) strips from carotid endarterectomy samples were classified into hard, intermediate and soft according to their incremental Young's modulus. Lipid and intraplaque haemorrhage/thrombus strips were classified as hard and soft. Idealised geometry-based 3D fluid-structure interaction analyses were performed to assess the impact of material property variability in predicting maximum principal stress (Stress-P1 ) and stretch (Stretch-P1 ). When FC was thick (1000 or 600 µm), Stress-P1 at the shoulder was insensitive to changes in material stiffness, whereas Stress-P1 at mid FC changed significantly. When FC was thin (200 or 65 µm), high stress concentrations shifted from the shoulder region to mid FC, and Stress-P1 became increasingly sensitive to changes in material properties, in particular at mid FC. Regardless of FC thickness, Stretch-P1 at these locations was sensitive to changes in material properties. Variability in tissue material properties influences both the location and overall stress/stretch value. This variability needs to be accounted for when interpreting the results of mechanical modelling. © 2015 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

  11. Relative atherosclerotic plaque volume by CT coronary angiography trumps conventional stenosis assessment for identifying flow-limiting lesions.

    Science.gov (United States)

    Kato, Nahoko; Kishi, Satoru; Arbab-Zadeh, Armin; Rybicki, Frank J; Tanimoto, Shuzou; Aoki, Jiro; Watanabe, Mika; Horiuchi, Yu; Furui, Koichi; Hara, Kazuhiro; Ibukuro, Kenji; Lima, Joao A C; Tanabe, Kengo

    2017-11-01

    The new methods for diagnosing the ischemia with coronary computed tomographic angiography (CTA) as a noninvasive test have been investigated. To compare the relative plaque volume to quantitative CTA and quantitative coronary angiography (QCA) for detecting flow-limiting coronary artery stenoses. We studied 49 patients with 55 intermediate lesions (30-69% diameter stenosis) who underwent CTA, coronary angiography (CAG), and FFR. CTA and QCA measures included lesion length, percent diameter stenosis (%DS), minimal lumen diameter (MLD), target main vessel percent plaque volume (%PV), lesion %PV, target main vessel percent lumen volume (%LV), and lesion %LV. FFR ≤0.80 was considered diagnostic of a flow-limiting lesion. The area under the receiver-operating characteristic curve (AUC) was used to determine the accuracy of detecting flow-limiting lesions. We also investigated the AUC of discrimination of flow-limiting lesion according to calcium score. Eighteen of 55 lesions (32.7%) had an FFR ≤0.80. Only vessel %PV differentiated between lesions with and without flow obstruction (67.6 vs. 62.7%, p = 0.018). The AUC for vessel %PV was greatest (0.76; 95% CI 0.61-0.87). The AUC for the discrimination of the flow-limiting lesions according to low calcium score (≤400) improved to 0.82 (95% CI 0.57-0.94). In intermediate coronary artery stenoses, vessel %PV is more accurate than conventional stenosis assessment for detecting flow-limiting lesions. In low calcium score, vessel %PV is more useful for diagnosis of ischemic heart disease compared with conventional quantitative measures.

  12. Flaxseed reverses atherosclerotic lesion formation and lowers lipoprotein(a) in ovarian hormone deficiency.

    Science.gov (United States)

    Campbell, Sara C; Bakhshalian, Neema; Sadaat, Raz L; Lerner, Megan R; Lightfoot, Stanley A; Brackett, Daniel; Arjmandi, Bahram H

    2013-11-01

    The incidence of cardiovascular disease dramatically increases during menopause, and postmenopausal women seek natural alternatives to hormone therapy. Flaxseed can slow the progression of atherosclerotic lesion formation; however, it is not known whether it can reverse formation that has already occurred. Seventy-two female Golden Syrian hamsters were randomly divided into six groups (n = 12), sham-operated (sham) or ovariectomized (ovx), and kept on the same diet for 120 days to allow for atherosclerotic lesion development. After this 120-day period, whole flaxseed was introduced to the diets of hamsters in three of the groups: group 1 (sham + casein); group 2 (ovx + casein); group 3 (ovx + 7.5% flaxseed); group 4 (ovx + 15% flaxseed); group 5 (ovx + 22.5% flaxseed); and group 6 (ovx + 17β-estradiol). This diet was maintained for an additional 120 days. Lesion regression was examined histologically, and serum was analyzed for total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, Apo A, Apo B, and lipoprotein(a). Results showed that 15% and 22.5% flaxseed, compared with ovx animals, significantly reduced lipoprotein(a) (4.4 mg/dL [ovx] vs 2.15 mg/dL [15% flaxseed] and 0.3 mg/dL [22.5% flaxseed]; P < 0.05) and Apo B (2.8 mg/dL [ovx] vs 2.4 mg/dL [15% flaxseed] and 2.5 mg/dL [22.5% flaxseed]). Flax reduced by 67% the number of animals with aortic arch lesions. All three doses of flax reduce the severity of lesion formation compared with ovx controls. These results support the efficacy of flaxseed in reducing cardiovascular disease risk.

  13. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice.

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    Ida Rune

    Full Text Available The importance of the gut microbiota (GM in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD, and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/- mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis

  14. Network analysis reveals a causal role of mitochondrial gene activity in atherosclerotic lesion formation.

    Science.gov (United States)

    Vilne, Baiba; Skogsberg, Josefin; Foroughi Asl, Hassan; Talukdar, Husain Ahammad; Kessler, Thorsten; Björkegren, Johan L M; Schunkert, Heribert

    2017-12-01

    Mitochondrial damage and augmented production of reactive oxygen species (ROS) may represent an intermediate step by which hypercholesterolemia exacerbates atherosclerotic lesion formation. To test this hypothesis, in mice with severe but genetically reversible hypercholesterolemia (i.e. the so called Reversa mouse model), we performed time-resolved analyses of mitochondrial transcriptome in the aortic arch employing a systems-level network approach. During hypercholesterolemia, we observed a massive down-regulation (>28%) of mitochondrial genes, specifically at the time of rapid atherosclerotic lesion expansion and foam cell formation, i.e. between 30 and 40 weeks of age. Both phenomena - down-regulation of mitochondrial genes and lesion expansion - were largely reversible by genetically lowering plasma cholesterol (by >80%, from 427 to 54 ± 31 mg/L) at 30 weeks. Co-expression network analysis revealed that both mitochondrial signature genes were highly connected in two modules, negatively correlating with lesion size and supported as causal for coronary artery disease (CAD) in humans, as expression-associated single nucleotide polymorphisms (eSNPs) representing their genes overlapped markedly with established disease risk loci. Within these modules, we identified the transcription factor estrogen related receptor (ERR)-α and its co-factors PGC1-α and -β, i.e. two members of the peroxisome proliferator-activated receptor γ co-activator 1 family of transcription regulators, as key regulatory genes. Together, these factors are known as major orchestrators of mitochondrial biogenesis and antioxidant responses. Using a network approach, we demonstrate how hypercholesterolemia could hamper mitochondrial activity during atherosclerosis progression and pinpoint potential therapeutic targets to counteract these processes. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.

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    Wei Yang

    2016-07-01

    Full Text Available Genome-wide association studies have revealed an association between coronary heart disease (CHD and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs and endothelial cells (ECs from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic

  16. Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction

    Science.gov (United States)

    Pu, Xiangyuan; Ren, Meixia; An, Weiwei; Zhang, Ruoxin; Yan, Shunying; Situ, Haiteng; He, Xinjie; Chen, Yequn; Tan, Xuerui; Xiao, Qingzhong; Tucker, Arthur T.; Caulfield, Mark J.; Ye, Shu

    2016-01-01

    Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD

  17. Surface modified gold nanoparticles for SERS based detection of vulnerable plaque formations (Conference Presentation)

    Science.gov (United States)

    Matthäus, Christian; Dugandžić, Vera; Weber, Karina; Cialla-May, Dana; Popp, Jürgen

    2017-02-01

    Cardiovascular diseases are the leading cause of death worldwide. Atherosclerosis is closely related to the majority of these diseases, as a process of thickening and stiffening of the arterial walls through accumulation of lipids, which is a consequence of aging and life style. Atherosclerosis affects all people in some extent, but not all arterial plaques will necessarily lead to the complications, such as thrombosis, stroke and heart attack. One of the greatest challenges in the risk assessment of atherosclerotic depositions is the detection and recognition of plaques which are unstable and prone to rupture. These vulnerable plaques usually consist of a lipid core that attracts macrophages, a type of white blood cells that are responsible for the degradation of lipids. It has been hypothesized that the amount of macrophages relates to the overall plaque stability. As phagocytes, macrophages also act as recipients for nanoscale particles or structures. Administered gold nanoparticles are usually rabidly taken up by macrophages residing within arterial walls and can therefore be indirectly detected. A very sensitive strategy for probing gold nanoparticles is by utilizing surface enhanced Raman scattering (SERS). By modifying the surface of these particles with SERS active labels it is possible to generate highly specific signals that exhibit sensitivity comparable to fluorescence. SERS labeled gold nanoparticles have been synthesized and the uptake dynamics and efficiency on macrophages in cell cultures was investigated using Raman microscopic imaging. The results clearly show that nanoparticles are taken up by macrophages and support the potential of SERS spectroscopy for the detection of vulnerable plaques. Acknowledgements: Financial support from the Carl Zeiss Foundation is highly acknowledged. The project "Jenaer Biochip Initiative 2.0" (03IPT513Y) within the framework "InnoProfile Transfer - Unternehmen Region" is supported by the Federal Ministry of

  18. Association of ideal cardiovascular health and calcified atherosclerotic plaque in the coronary arteries: the National Heart, Lung, and Blood Institute Family Heart Study.

    Science.gov (United States)

    Robbins, Jeremy M; Petrone, Andrew B; Carr, J Jeffrey; Pankow, James S; Hunt, Steven C; Heiss, Gerardo; Arnett, Donna K; Ellison, R Curtis; Gaziano, J Michael; Djoussé, Luc

    2015-03-01

    The American Heart Association (AHA) established recommendations based on 7 ideal health behaviors and factors with the goal of improving cardiovascular health (CVH) and reducing both morbidity and mortality from cardiovascular disease by 20% by 2020. Few studies have investigated their association with subclinical coronary heart disease. We sought to examine whether the 7 AHA CVH metrics were associated with calcified atherosclerotic plaque in the coronary arteries. In a cross-sectional design, we studied 1,731 predominantly white men and women from the National Heart, Lung, and Blood Institute Family Heart Study without prevalent coronary heart disease. Diet was assessed by a semiquantitative food frequency questionnaire. Coronary artery calcium (CAC) was measured by cardiac computed tomography. We defined prevalent CAC using an Agatston score of 100+ and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age was 56.8 years, and 41% were male. The median number of ideal CVH metrics was 3, and no participant met all 7. There was a strong inverse relationship between number of ideal CVH metrics and prevalent CAC. Odds ratios (95% CI) for CAC of 100+ were 1.0 (reference), 0.37 (0.29-0.45), 0.35 (0.26-0.44), and 0.27 (0.20-0.36) among subjects with 0 to 1, 2, 3, and 4+ ideal CVH metrics, respectively (P = .0001), adjusting for sex, age, field center, alcohol, income, education, and energy consumption. These data demonstrate a strong and graded inverse relationship between AHA ideal CVH metrics and prevalent CAC in adult men and women. Published by Elsevier Inc.

  19. The presence of remodeled and mixed atherosclerotic plaques at coronary ct angiography predicts major cardiac adverse events - The CAFÉ-PIE Study.

    Science.gov (United States)

    Guaricci, Andrea Igoren; Pontone, Gianluca; Brunetti, Natale Daniele; De Rosa, Fiorella; Montrone, Deodata; Guglielmo, Marco; Mushtaq, Saima; Fusini, Laura; Maffei, Erica; Cademartiri, Filippo; Macarini, Luca; Andreini, Daniele; Di Biase, Matteo; Bartorelli, Antonio L; Pepi, Mauro

    2016-07-15

    It is still unclear how to exploit information made available by coronary computed tomography angiography (CCTA) on coronary artery disease (CAD) features in order to better predicting major adverse cardiac events (MACEs). Aim of this study was to validate the prognostic role of a comprehensive and simplified CT-derived score in patients evaluated for suspected CAD. A prospective registry included 477 consecutive symptomatic patients without known CAD who underwent clinically-indicated CCTA. All patients were followed-up for MACE occurrence for a period of 49±15-month. The mean CT Score was 10.5±10.8, with a MACE rate of 11.3%. There was a stepwise relationship between MACE rate during follow-up and CT Score values. MACEs were 1.9% in patients with CT Score30 (OR 46.1, 95% C.I. 13.0-162.9 vs. reference group, p<0.001) (p for trend <0.001). At ROC curve analysis, CT Score was the best predictor of MACE (AUC: 0.81, CI 95%: 0.78-0.84) as compared to Diamond and Forrester score (p<0.001), segment stenosis score (p<0.05) and segment involved score (p<.0.01). The use of an integrated score obtained with CCTA and based on the presence of remodeled and mixed atherosclerotic coronary plaques may improve MACE prediction in symptomatic patients at intermediate risk outweighing that provided by standard clinical and CCTA scores. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Dihydrocapsaicin Attenuates Plaque Formation through a PPARγ/LXRα Pathway in apoE(-/- Mice Fed a High-Fat/High-Cholesterol Diet.

    Directory of Open Access Journals (Sweden)

    Yan-Wei Hu

    Full Text Available Atherosclerosis is a chronic inflammatory disease and represents the major cause of cardiovascular morbidity and mortality. There is evidence that dihydrocapsaicin (DHC can exert multiple pharmacological and physiological effects. Here, we explored the effect of DHC in atherosclerotic plaque progression in apoE(-/- mice fed a high-fat/high-cholesterol diet.apoE(-/- mice were randomly divided into two groups and fed a high-fat/high-cholesterol diet with or without DHC for 12 weeks. We demonstrated that cellular cholesterol content was significantly decreased while apoA1-mediated cholesterol efflux was significantly increased following treatment with DHC in THP-1 macrophage-derived foam cells. We also observed that plasma levels of TG, LDL-C, VLDL-C, IL-1β, IL-6, TNF-α and CRP were markedly decreased while plasma levels of apoA1 and HDL-C were significantly increased, and consistent with this, atherosclerotic lesion development was significantly inhibited by DHC treatment of apoE(-/- mice fed a high-fat/high-cholesterol diet. Moreover, treatment with both LXRα siRNA and PPARγ siRNA made the up-regulation of DHC on ABCA1, ABCG1, ABCG5, SR-B1, NPC1, CD36, LDLR, HMGCR, apoA1 and apoE expression notably abolished while made the down-regulation of DHC on SRA1 expression markedly compensated. And treatment with PPARγ siRNA made the DHC-induced up-regulation of LXRα expression notably abolished while treatment with LXRα siRNA had no effect on DHC-induced PPARγ expression.These observations provide direct evidence that DHC can significantly decrease atherosclerotic plaque formation involving in a PPARγ/LXRα pathway and thus DHC may represent a promising candidate for a therapeutic agent for the treatment or prevention of atherosclerosis.

  1. 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

  2. The effect of toothpaste containing Kayu Sugi extract on plaque formation

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    Widowati W

    2009-03-01

    Full Text Available Background: Although many researches had revealed the beneficial effect of Kayu Sugi as a chewing stick, study on the effectiveness of its extract in toothpaste is still inadequate. Purpose: The objective of this study was to compare the effect of toothpaste, with and without Kayu Sugi extract on preventing plaque formation. Methods: The study consists of two sessions which was separated by three days washout period. The subjects were given two types of toothpaste, with and without Kayu Sugi extract to be used in the first and second session separately. The subjects were polished and plaque score were measured after one hour for the first quadrant, two hours later for the second quadrant and after four hours for the third/fourth quadrant. Subjects were not allowed to eat, drink or rinse during this four hours period. The procedures were repeated for the second session after three days washout period. The plaque score were recorded as absent (code 0 and present (code 1, and only labial and palatal/lingual surfaces of each tooth were used for plaque scoring. result: The study showed that there was no significant difference of the amount of plaque formed after polishing using two different toothpastes, with and without Kayu Sugi extract. Conclusion: We concluded that toothpaste with or without Kayu Sugi extract give similar level in preventing plaque formation.

  3. The influence of xylitol containing toothpaste on plaque formation inhibition on fixed bridge

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    Hamim Fithrony

    2009-09-01

    Full Text Available Background: Plaque is the main cause of teeth and periodontal tissue damage, which usually accumulates on crown surfaces. To avoid this, plaque control is the best way that not only has a close connection to oral hygiene but also become important element in dental practice. Previously, xylitol was used as alternative sweetener for diabetic patients, but later it is used to maintain healthy teeth. Xylitol is capable to inhibit Streptococcus mutans growth which changes sugar and other carbohydrate into acid, because xylitol cannot be fermented. Purpose: This study was aimed to understand the inhibition capability of toothpaste containing xylitol to plaque formation on fixed bridge. Methods: This clinical experiment study was carried out in fifteen patients wearing fixed bridge at Prosthodontics Department, Faculty of Dentistry, Airlangga University in Surabaya from 2005 to 2008. Samples were based on selective random sampling technique. Plaque index was analyzed by Mann Whitney test. Result: This study showed that there was significant difference of plaque scores in patients who brush their teeth using xylitol containing toothpaste compared to the control group (placebo. Conclusion: Xylitol was capable to inhibit plaque formation on fixed bridge.

  4. The collagen cross-linking enzyme lysyl oxidase is associated with the healing of human atherosclerotic lesions.

    Science.gov (United States)

    Ovchinnikova, O A; Folkersen, L; Persson, J; Lindeman, J H N; Ueland, T; Aukrust, P; Gavrisheva, N; Shlyakhto, E; Paulsson-Berne, G; Hedin, U; Olofsson, P S; Hansson, G K

    2014-11-01

    Acute clinical complications of atherosclerosis such as myocardial infarction (MI) and ischaemic stroke are usually caused by thrombus formation on the ruptured plaque surface. Collagen, the main structural protein of the fibrous cap, provides mechanical strength to the atherosclerotic plaque. The integrity of the fibrous cap depends on collagen fibre cross-linking, a process controlled by the enzyme lysyl oxidase (LOX). We studied atherosclerotic plaques from human carotid endarterectomies. LOX was strongly expressed in atherosclerotic lesions and detected in the regions with ongoing fibrogenesis. Higher LOX levels were associated with a more stable phenotype of the plaque. In the studied population, LOX mRNA levels in carotid plaques predicted the risk for future MI. Within the lesion, LOX mRNA levels correlated positively with levels of osteoprotegerin (OPG) and negatively with markers of immune activation. The amount of LOX-mediated collagen cross-links in plaques correlated positively also with serum levels of OPG. Lysyl oxidase may contribute to the healing of atherosclerotic lesions and to the prevention of its lethal complications. Mediators of inflammation may control LOX expression in plaques and hence plaque stability. © 2014 The Association for the Publication of the Journal of Internal Medicine.

  5. In vivo distribution of single chain variable fragment (scFv) against atherothrombotic oxidized LDL/β2-glycoprotein I complexes into atherosclerotic plaques of WHHL rabbits: Implication for clinical PET imaging.

    Science.gov (United States)

    Sasaki, Takanori; Kobayashi, Kazuko; Kita, Shoichi; Kojima, Kazuo; Hirano, Hiroyuki; Shen, Lianhua; Takenaka, Fumiaki; Kumon, Hiromi; Matsuura, Eiji

    2017-02-01

    Oxidized LDL (oxLDL) can exist as a complex with β2-glycoprotein I (β2GPI) in plasma/serum of patients with non-autoimmune atherosclerotic disease or antiphospholipid syndrome (APS). Nonetheless, direct in vivo evidence supporting the pathophysiological involvement of oxLDL/β2GPI complexes and specific autoantibody against the complexes in developing atherothrombosis has yet been established. In the present study, we demonstrated in vivo distribution of single chain variable fragment of IgG anti-oxLDL/β2GPI complexes (3H3-scFv) in Watanabe heritable hyperlipidemic (WHHL) rabbits by PET/CT imaging. An antibody-based PET probe, 64Cu-3H3-scFv, was established, and WHHL rabbits were applied for a non-autoimmune atherosclerotic model to demonstrate in vivo distribution of the probe. 3H3-scFv has exhibits specificity towards β2GPI complexed with oxLDL but neither a free form of β2GPI nor oxLDL alone. Post-intravenous administration of 64Cu-3H3-scFv into WHHL rabbits has demonstrated a non-invasive approach for in vivo visualization of atherosclerotic lesion. The imaging probe achieved ideal blood clearance and distribution for optimal imaging capacity in 24h, significantly shorter than that of an intact IgG-based imaging probe. 64Cu-3H3-scFv targeted on atherosclerotic plaques in aortas of WHHL rabbits where extensive accumulation of lipid deposits was observed by lipid staining and autoradiography. The accumulation of 64Cu-3H3-scFv in aortic segments of WHHL rabbits was 2.8-folds higher than that of controls (p=0.0045). The present in vivo evidence supports the pathophysiological involvement of oxLDL/β2GPI complexes in atherosclerotic complications of WHHL rabbits. 64Cu-3H3-scFv represents a novel PET imaging probe for non-invasive pathophysiological assessment of oxLDL/β2GPI complexes accumulated in atherosclerotic plaques. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. The time window of MRI of murine atherosclerotic plaques after administration of CB2 receptor targeted micelles: inter-scan variability and relation between plaque signal intensity increase and gadolinium content of inversion recovery prepared versus non-prepared fast spin echo.

    Science.gov (United States)

    te Boekhorst, B C M; Bovens, S M; van de Kolk, C W A; Cramer, M J M; Doevendans, P A F M; ten Hove, M; van der Weerd, L; Poelmann, R; Strijkers, G J; Pasterkamp, G; van Echteld, C J A

    2010-10-01

    Single fast spin echo scans covering limited time frames are mostly used for contrast-enhanced MRI of atherosclerotic plaque biomarkers. Knowledge on inter-scan variability of the normalized enhancement ratio of plaque (NER(plaque)) and relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo is limited. Study aims were: evaluation of (1) timing of MRI after intravenous injection of cannabinoid-2 receptor (CB2-R) (expressed by human and mouse plaque macrophages) targeted micelles; (2) inter-scan variability of inversion-recovery fast spin echo and fast spin echo; (3) relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo and fast spin echo. Inversion-recovery fast spin echo/fast spin echo imaging was performed before and every 15 min up to 48 h after injection of CB2-R targeted or control micelles using several groups of mice measured in an interleaved fashion. NER(plaque) (determined on inversion-recovery fast spin echo images) remained high (∼2) until 48 h after injection of CB2-R targeted micelles, whereas NER(plaque) decreased after 36 h in the control group. The inter-scan variability and relation between NER(plaque) and gadolinium (assessed with inductively coupled plasma- mass spectrometry) were compared between inversion-recovery fast spin echo and fast spin echo. Inter-scan variability was higher for inversion-recovery fast spin echo than for fast spin echo. Although gadolinium and NER(plaque) correlated well for both techniques, the NER of plaque was higher for inversion-recovery fast spin echo than for fast spin echo. In mice injected with CB2-R targeted micelles, NER(plaque) can be best evaluated at 36-48 h post-injection. Because NER(plaque) was higher for inversion-recovery fast spin echo than for fast spin echo, but with high inter-scan variability, repeated inversion-recovery fast spin echo imaging and averaging of the obtained NER(plaque) values is recommended

  7. Comparing the three color pounehh tooth paste with the conventional one in preventing the formation of the microbial plaque

    OpenAIRE

    Ebadifar A; Naghibi A.; Valaie N.; Ramezani GH.; Sadat Mansori S.

    2008-01-01

    "nBackground and Aim: Plaque control has always been important in preventive dentistry. Various methods and materials have been introduced for this purpose. Recently a three-colored tooth paste has been introduced which claims to prevent plaque formation. The aim of this study was to compare three-colored pouneh tooth paste containing triclosan with the conventional one in preventing plaque formation. "nMaterials and Methods: This was a randomized double blind cross over clinical tr...

  8. Anti-atherosclerotic effect of traditional fermented cheese whey in atherosclerotic rabbits and identification of probiotics.

    Science.gov (United States)

    Nabi, Xin-Hua; Ma, Chun-Yan; Manaer, Tabusi; Heizati, Mulalibieke; Wulazibieke, Baheti; Aierken, Latipa

    2016-08-24

    Traditional fermented cheese whey (TFCW), containing probiotics, has been used both as a dairy food with ethnic flavor and a medicine for cardiovascular disease, especially regulating blood lipid among Kazakh. We therefore investigated anti-atherosclerotic effects of TFCW in atherosclerotic rabbits and identified lactic acid bacteria (LAB) and yeasts in TFCW. Atherosclerotic rabbits were induced by administration of atherosclerotic diet for 12 weeks and divided randomly into three groups and treated for 4 weeks with Simvastatin (20 mg/kg) or TFCW (25 mg/kg) and (50 mg/kg). In addition, a normal control group and an atherosclerotic group were used for comparison. All drugs were intragastrical administered once daily 10 mL/kg for 4 weeks. Body weight (BW), lipid profiles, C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were tested and theromatous plaques and the number of foam cells and infiltrating fibroblast cells in the thoracic aorta endothelium was evaluated by hematoxylin and eosin stainin. LAB and yeasts were isolated and purified by conventional techniques and identified using morphological and biochemical properties as well as gene sequences analysis. After 4 weeks of treatment, high and low dose TFCW decreased serum TC, TG, LDLC, CRP, VCAM-1 and ICAM-1 (P < 0.05) compared to atherosclerotic group, and increased HDL-C (P < 0.05) compared to normal controls. Histological analysis showed TFCW reduced VCAM-1 expression and formation of atheromatous plaques on the aortic endothelium of atherosclerotic rabbits. Seven classes of LBA from two different genera including Lactobacillus brevis, Lactobacillus kefianofaciens, Lactobacillus helveticus, Lactobacillus Casei, Lactobacillus plantarum, Lactobacillus kefiri and Lactococcus lactic as well as 2 classes of yeasts from two different genera including Saccharomyces unisporus and Issatchenkia orientalis were isolated and identified

  9. The effect of periodontal treatment on the salivary bacterial load and early plaque formation

    NARCIS (Netherlands)

    Dahan, M; Timmerman, MF; Van Winkelhoff, AJ; Van der Velden, U

    2004-01-01

    Aim: The purpose of the present study was to investigate in periodontitis patients the relationship between the number of bacteria in the saliva and the amount of de novo plaque formation before and after treatment. Methods: At baseline, before any treatment was provided, patients rinsed with 10 ml

  10. The effect of a chlorhexidine regimen on de novo plaque formation.

    Science.gov (United States)

    Sekino, Satoshi; Ramberg, Per; Uzel, Naciye Guzin; Socransky, Sigmund; Lindhe, Jan

    2004-08-01

    To evaluate the effect of a pretreatment regimen that combined meticulous mechanical tooth cleaning with the daily use of chlorhexidine (rinse, gargle and tongue application) on de novo plaque formation and on the recolonization of various microbiological species in plaque and saliva during a 4-day period of no oral hygiene. Ten subjects aged 24-36 years with gingivitis were recruited. The study was designed as a double blind cross-over clinical trial including two phases. Each experimental phase comprised one preparatory period of 7 days and one plaque accumulation period of 4 days. During the preparatory period, the volunteers (i) performed meticulous mechanical tooth cleaning using toothbrush and dentifrice and (ii) were, in addition, given two sessions of professional tooth cleaning (PTC) The final PTC was delivered after bacterial sampling had been made on Day 0. In the Control group, no additional plaque control measures were included. In the Test group, the participants in addition to the mechanical measures (i) rinsed twice daily, for 60 s each time with a 0.2% chlorhexidine solution, (ii) gargled twice daily for 10 s with the chlorhexidine preparation, and finally (iii) brushed the dorsum of the tongue for 60 s, twice daily, with a 1.0% chlorhexidine gel. During the 4-day plaque accumulation period, the participants abstained from all mechanical and chemical plaque control measures. On Days 0, 1, 2 and 4 the quantity and quality of plaque formed was assessed by clinical means and by DNA probe techniques. The microbiota of the saliva was studied in samples obtained on Days 0 and 4. It was demonstrated that chlorhexidine used as a mouthrinse combined with gargling and tongue application during the preparatory period significantly retarded the amount of plaque that formed on tooth surfaces during the following 4 days of no oral hygiene. Further, the number of microorganisms present in the biofilm representing Days 0, 1 and 2 of the "plaque accumulation period

  11. Some effects of mouthrinses containing salifluor on de novo plaque formation and developing gingivitis.

    Science.gov (United States)

    Furuichi, Y; Ramberg, P; Lindhe, J; Nabi, N; Gaffar, A

    1996-08-01

    Three clinical trials were carried out to evaluate the effects of mouthrinses containing 5n-octanoyl-3'-trifluormethylsalicylanilide (salifluor) on plaque and gingivitis. Each trial was performed as a double-blind, randomised and cross-over designed study (studies 1, 2 and 3). In each study, 10 young individuals with healthy gingiva abolished all means of mechanical plaque control during the course of the experimental period including 6 x 4 days (study 1), 3 x 18 days (study 2) and 3 x 14 days (study 3). They rinsed, 2 x daily, with various mouthwash preparations for 4 days (study 1), for the last 4 days of a 18 day period (study 2) or for 14 days (study 3). 6 (control, vehicle control, 0.08%, 0.12% and 0.2% salifluor and 0.12% chlorhexidine), 3 (control, 0.12% salifluor and 0.12% chlorhexidine) and 3 (control, 0.12% salifluor and 0.12% chlorhexidine) mouthwash preparations were tested in studies 1, 2 and 3, respectively. The findings of study 1 indicated that (i) mouthrinses containing salifluor were significantly more effective than control rinses and that (ii) the salifluor mouthrinses were equally effective as the 0.12% chlorhexidine mouthrinse, in retarding 4-day de novo plaque formation. The findings of study 2 indicated that (i) the mouthrinse containing 0.12% salifluor retarded de novo plaque formation to the same extent as the 0.12% chlorhexidine mouthrinse at healthy as well as at inflamed sites but that (ii) the anti-plaque effects of the salifluor and chlorhexidine mouthrinses were significantly smaller at sites with inflamed than with healthy gingiva. In study 3, it was observed that there was no significant difference between the 0.12% salifluor and 0.12% chlorhexidine mouthrinses in retarding de novo plaque formation and the development of gingivitis during a 14-day period of no mechanical plaque control. Thus, the results of the 3 clinical trials demonstrated the potential of salifluor as an effective anti-plaque and anti-inflammatory agent.

  12. Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial

    OpenAIRE

    amrutesh, sunita; Malini, J; Tandur, Prakash S; Patki, Pralhad S

    2010-01-01

    Background The aim of this study was to evaluate the efficacy and safety of herbal dental cream in comparison to fluoride dental cream. Objectives Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial. Methods One hundred and two patients with established dental plaque were randomly assigned to either herbal dental group or fluoride dental group for six weeks in a double-blind design. Improvement in plaque index, oral hyg...

  13. Oral glucose tolerance test predicts increased carotid plaque burden in patients with acute coronary syndrome.

    Directory of Open Access Journals (Sweden)

    Thorarinn A Bjarnason

    Full Text Available Type 2 diabetes and prediabetes are established risk factors for atherosclerosis. The aim of this study was to evaluate the atherosclerotic plaque burden in the carotid arteries of patients with acute coronary syndrome according to their glycemic status.Patients with acute coronary syndrome and no previous history of type 2 diabetes were consecutively included in the study. Glucose metabolism was evaluated with fasting glucose in plasma, HbA1c and a standard two-hour oral glucose tolerance test. Atherosclerotic plaque in the carotid arteries was evaluated with a standardized ultrasound examination where total plaque area was measured and patients classified as having no plaque or a significant plaque formation.A total of 245 acute coronary syndrome patients (male 78%, 64 years (SD: 10.9 were included. The proportion diagnosed with normal glucose metabolism, prediabetes and type 2 diabetes was 28.6%, 64.1% and 7.3%, respectively. A significant atherosclerotic plaque was found in 48.5%, 66.9% and 72.2% of patients with normal glucose metabolism, prediabetes and type 2 diabetes, respectively. An incremental increase in total plaque area was found from normal glucose metabolism to prediabetes (25.5% and from normal glucose metabolism to type 2 diabetes (35.9% (p = 0.04. When adjusted for conventional cardiovascular risk factors the OR of having significant atherosclerotic plaque in the carotid arteries was 2.17 (95% CI 1.15-4.15 for patients with newly diagnosed dysglycemia compared to patients with normal glucose metabolism. When additionally adjusted for the 2-hour plasma glucose after glucose loading (2hPG the OR attenuated to 1.77 (95% CI 0.83-3.84.Newly detected dysglycemia is an independent predictor of significant atherosclerotic plaque in the carotid arteries with oral glucose tolerance test as a major determinant of carotid plaque burden in this group of individuals with acute coronary syndrome.

  14. Systemic lupus erythematosus: the influence of disease-related and classical risk factors on intima media thickness and prevalence of atherosclerotic plaques--a preliminary report. Beneficial effect of immunosuppressive treatment on carotid intima media thickness.

    Science.gov (United States)

    Kisiel, Bartłomiej; Kruszewski, Robert; Juszkiewicz, Aleksandra; Raczkiewicz, Anna; Bachta, Artur; Kłos, Krzysztof; Duda, Krzysztof; Saracyn, Marek; Szymański, Konrad; Młozniak-Cieśla, Agnieszka; Grabowska-Jodkowska, Agnieszka; Olesińska, Marzena; Bogusławska-Walecka, Romana; Niemczyk, Stanisław; Płoski, Rafał; Tłustochowicz, Witold

    2015-04-01

    The risk of cardiovascular disease is increased in systemic lupus erythematosus (SLE). A meta-analysis showed increased carotid intima media thickness (IMT) in SLE. The aim of this study was to assess the influence of different SLE characteristics and treatment regimens on IMT and atherosclerotic plaques. One hundred and three SLE patients and 95 age- and sex-matched control subjects were included in the study. MT was measured in the common carotid arteries bilaterally. Common carotid arteries, internal carotid arteries and superficial femoral arteries were also screened for the presence of plaques. The presence of plaques was correlated with age (P = 0.00002), male sex (P = 0.034), Framingham 10-year risk score (P body mass index (P = 0.026), Framingham 10-year risk score (P < 0.001), total cholesterol concentration (P = 0.002), LDL cholesterol concentration (P = 0.007), SLICC/ACR (P = 0.035), hypertension (P = 0.002), immunologic disorder (P = 0.00008) and discontinuous treatment with immunosuppressive drugs (P = 0.043). We found a correlation between atherosclerosis and several classical cardiovascular risk factors and disease-related factors. A beneficial effect of continuous immunosuppressive treatment on IMT suggests that appropriate disease control with steroid-sparing agents may protect against atherosclerosis in SLE patients.

  15. Model studies on dental plaque formation: deoxyhexoses in Actinomyces viscosus.

    Science.gov (United States)

    Tylenda, C A; Charon, D; Lombardi, F P; Gabriel, O

    1979-02-01

    A careful examination of two strains of Actinomyces viscosus, T14V (virulent) and T14AV (avirulent), revealed no qualitative or quantitative difference in 6-deoxyhexose content of their cell surface. For a further study of the role of these sugars in cell surface-related phenomena, the stereochemical configuration of deoxyhexoses of A. viscosus T14 was established by two complementary approaches. (i) Examination of the biosynthetic pathway was found to lead to the formation of both 6-deoxy-l-talose and 6-deoxy-l-mannose and showed no differences in the ability of either bacterial strain, A. viscosus T14V or T14AV, to produce the precursors of these cell wall components. The biosynthetic pathway for 6-deoxy-l-talose and 6-deoxy-l-mannose was found to originate from deoxy-thymidine diphosphate (dTDP)-d-glucose, which in turn is converted to dTDP-4-keto-6-deoxy-d-glucose. Epimerization at carbons 3 and 5 of the hexose moiety of dTDP-4-keto-6-deoxy-d-glucose is followed by stereospecific reduction with reduced nicotinamide adenine dinucleotide phosphate to yield dTDP-6-deoxy-l-talose and dTDP-6-deoxy-l-mannose. In cell-free extracts of both A. viscosus T14 and T14AV, an identical ratio of 6-deoxy-l-talose to 6-deoxy-l-mannose of 1:8 was produced. Known precursors for the d-isomers of the same 6-deoxyhexoses such as guanosine diphosphate-d-mannose and dTDP-d-mannose were not converted by A. viscosus T14 cell-free extracts. (ii) Isolation of 6-[U-(14)C]deoxytalose and 6-[U-(14)C]deoxymannose from both strains of A. viscosus T14 was carried out by growing cells in a medium containing d-[U-(14)C]glucose. Again no qualitative or quantitative difference was noticeable between the two strains when 6-deoxy-hexoses were released from whole cells or purified cell walls by acid hydrolysis. Radioactive 6-[U-(14)C]deoxytalose isolated from the cell surface was used in an isotope dilution experiment to establish the stereochemical configuration of this 6-deoxyhexose. The radioactive

  16. Model Studies on Dental Plaque Formation: Deoxyhexoses in Actinomyces viscosus†

    Science.gov (United States)

    Tylenda, C. A.; Charon, D.; Lombardi, F. P.; Gabriel, O.

    1979-01-01

    A careful examination of two strains of Actinomyces viscosus, T14V (virulent) and T14AV (avirulent), revealed no qualitative or quantitative difference in 6-deoxyhexose content of their cell surface. For a further study of the role of these sugars in cell surface-related phenomena, the stereochemical configuration of deoxyhexoses of A. viscosus T14 was established by two complementary approaches. (i) Examination of the biosynthetic pathway was found to lead to the formation of both 6-deoxy-l-talose and 6-deoxy-l-mannose and showed no differences in the ability of either bacterial strain, A. viscosus T14V or T14AV, to produce the precursors of these cell wall components. The biosynthetic pathway for 6-deoxy-l-talose and 6-deoxy-l-mannose was found to originate from deoxy-thymidine diphosphate (dTDP)-d-glucose, which in turn is converted to dTDP-4-keto-6-deoxy-d-glucose. Epimerization at carbons 3 and 5 of the hexose moiety of dTDP-4-keto-6-deoxy-d-glucose is followed by stereospecific reduction with reduced nicotinamide adenine dinucleotide phosphate to yield dTDP-6-deoxy-l-talose and dTDP-6-deoxy-l-mannose. In cell-free extracts of both A. viscosus T14 and T14AV, an identical ratio of 6-deoxy-l-talose to 6-deoxy-l-mannose of 1:8 was produced. Known precursors for the d-isomers of the same 6-deoxyhexoses such as guanosine diphosphate-d-mannose and dTDP-d-mannose were not converted by A. viscosus T14 cell-free extracts. (ii) Isolation of 6-[U-14C]deoxytalose and 6-[U-14C]deoxymannose from both strains of A. viscosus T14 was carried out by growing cells in a medium containing d-[U-14C]glucose. Again no qualitative or quantitative difference was noticeable between the two strains when 6-deoxy-hexoses were released from whole cells or purified cell walls by acid hydrolysis. Radioactive 6-[U-14C]deoxytalose isolated from the cell surface was used in an isotope dilution experiment to establish the stereochemical configuration of this 6-deoxyhexose. The radioactive sugar

  17. Reproducibility of coronary atherosclerotic plaque characteristics in populations with low, intermediate, and high prevalence of coronary artery disease by multidetector computer tomography: a guide to reliable visual coronary plaque assessments.

    Science.gov (United States)

    de Knegt, Martina C; Linde, Jesper J; Fuchs, Andreas; Nordestgaard, Børge G; Køber, Lars V; Hove, Jens D; Kofoed, Klaus F

    2016-10-01

    To evaluate the interobserver agreement of visual coronary plaque characteristics by 320-slice multidetector computed tomography (MDCT) in three populations with low, intermediate and high CAD prevalence and to identify determinants for the reproducible assessment of these plaque characteristics. 150 patients, 50 asymptomatic subjects from the general population (low CAD prevalence), 50 symptomatic non-acute coronary syndrome (non-ACS) patients (intermediate CAD prevalence), and 50 ACS patients (high CAD prevalence), matched according to age and gender, were retrospectively enrolled. All coronary segments were evaluated for overall image quality, evaluability, presence of CAD, coronary stenosis, plaque composition, plaque focality, and spotty calcification by four readers. Interobserver agreement was assessed using Fleiss' Kappa (κ) and intra-class correlation (ICC). Widely used clinical parameters (overall scan quality, presence of CAD, and determination of coronary stenosis) showed good agreement among the four readers, (ICC = 0.66, κ = 0.73, ICC = 0.74, respectively). When accounting for heart rate, body mass index, plaque location, and coronary stenosis above/below 50 %, interobserver agreement for plaque composition, presence of CAD, and coronary stenosis improved to either good or excellent, (κ = 0.61, κ = 0.81, ICC = 0.78, respectively). Spotty calcification was the least reproducible parameter investigated (κ = 0.33). Across subpopulations, reproducibility of coronary plaque characteristics generally decreased with increasing CAD prevalence except for plaque composition, (limits of agreement: ±2.03, ±1.96, ±1.79 for low, intermediate and high CAD prevalence, respectively). 320-slice MDCT can be used to assess coronary plaque characteristics, except for spotty calcification. Reproducibility estimates are influenced by heart rate, body size, plaque location, and degree of luminal stenosis.

  18. Oral Administration of Thioflavin T Prevents Beta Amyloid Plaque Formation in Double Transgenic AD Mice.

    Science.gov (United States)

    Sarkar, Sumit; Raymick, James; Ray, Balmiki; Lahiri, Debomoy K; Paule, Merle G; Schmued, Larry

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily composed of phosphorylated tau protein. Although numerous agents have been considered as providing protection against AD, identification of potential agents with neuroprotective ability is limited. Thioflavin T has been used in the past to stain amyloid beta plaques in brain. In this study, Thioflavin T (ThT) and vehicle (infant formula) were administered orally by gavage to transgenic (B6C3 APP PS1; AD-Tg) mice beginning at 4 months age and continuing until sacrifice at 9 months of age at 40 mg/kg dose. The number of amyloid plaques was reduced dramatically by ThT treatment in both male and female transgenic mice compared to those in control mice. Additionally, GFAP and Amylo-Glo labeling suggest that astrocytic hypertrophy is minimized in ThT-treated animals. Similarly, CD68 labeling, which detects activated microglia, along with Amylo-Glo labeling, suggests that microglial activation is significantly less in ThT-treated mice. Both Aβ-40 and Aβ-42 concentrations in blood rose significantly in the ThT-treated animals suggesting that ThT may inhibit the deposition, degradation, and/or clearance of Aβ plaques in brain.

  19. Reproducibility of coronary atherosclerotic plaque characteristics in populations with low, intermediate, and high prevalence of coronary artery disease by multidetector computer tomography

    DEFF Research Database (Denmark)

    de Knegt, Martina C; Linde, Jesper J; Fuchs, Andreas

    2016-01-01

    coronary segments were evaluated for overall image quality, evaluability, presence of CAD, coronary stenosis, plaque composition, plaque focality, and spotty calcification by four readers. Interobserver agreement was assessed using Fleiss' Kappa (κ) and intra-class correlation (ICC). Widely used clinical...... parameters (overall scan quality, presence of CAD, and determination of coronary stenosis) showed good agreement among the four readers, (ICC = 0.66, κ = 0.73, ICC = 0.74, respectively). When accounting for heart rate, body mass index, plaque location, and coronary stenosis above/below 50 %, interobserver....... Reproducibility estimates are influenced by heart rate, body size, plaque location, and degree of luminal stenosis....

  20. Reduced Dental Plaque Formation in Dogs Drinking a Solution Containing Natural Antimicrobial Herbal Enzymes and Organic Matcha Green Tea.

    Science.gov (United States)

    Lindinger, Michael I

    2016-01-01

    The results of an exploratory, multicenter clinical study confirmed the hypothesis that a novel, natural, and safe oral care product (OCP) reduced the rate of plaque formation on teeth of dogs consuming the OCP (antimicrobial plant-derived enzymes, organic matcha green tea, cultured dextrose, sodium bicarbonate, and ascorbic acid) compared to controls. Healthy dogs without periodontitis, of varying breeds, sex, and age, were recruited and enrolled, using nonrandomized stratification methods, into a control and treatment groups. Treatment group dogs drank only water into which OCP was suspended, for 28 days. Control group dogs drank their normal household water. On day 0 all teeth were cleaned by a veterinarian and gingivitis was assessed. On days 14, 21, and 28 plaque index, plaque thickness, gingivitis, freshness of breath, and general health were assessed. Over the 28 days of study, dogs on the OCP had significant reduction in plaque index and plaque thickness compared to controls. By day 14 OCP reduced plaque formation by 37%; the 28-day reduction in plaque index and coverage averaged 22% with no measurable gingivitis or calculus. Conclusion. Using the OCP attenuated dental plaque formation when consumed as normal drinking water and in the absence of other modes of oral care.

  1. Reduced Dental Plaque Formation in Dogs Drinking a Solution Containing Natural Antimicrobial Herbal Enzymes and Organic Matcha Green Tea

    Directory of Open Access Journals (Sweden)

    Michael I. Lindinger

    2016-01-01

    Full Text Available The results of an exploratory, multicenter clinical study confirmed the hypothesis that a novel, natural, and safe oral care product (OCP reduced the rate of plaque formation on teeth of dogs consuming the OCP (antimicrobial plant-derived enzymes, organic matcha green tea, cultured dextrose, sodium bicarbonate, and ascorbic acid compared to controls. Healthy dogs without periodontitis, of varying breeds, sex, and age, were recruited and enrolled, using nonrandomized stratification methods, into a control and treatment groups. Treatment group dogs drank only water into which OCP was suspended, for 28 days. Control group dogs drank their normal household water. On day 0 all teeth were cleaned by a veterinarian and gingivitis was assessed. On days 14, 21, and 28 plaque index, plaque thickness, gingivitis, freshness of breath, and general health were assessed. Over the 28 days of study, dogs on the OCP had significant reduction in plaque index and plaque thickness compared to controls. By day 14 OCP reduced plaque formation by 37%; the 28-day reduction in plaque index and coverage averaged 22% with no measurable gingivitis or calculus. Conclusion. Using the OCP attenuated dental plaque formation when consumed as normal drinking water and in the absence of other modes of oral care.

  2. Antimicrobial photodynamic therapy suppresses dental plaque formation in healthy adults: a randomized controlled clinical trial.

    Science.gov (United States)

    Ichinose-Tsuno, Akiko; Aoki, Akira; Takeuchi, Yasuo; Kirikae, Teruo; Shimbo, Takuro; Lee, Masaichi-Chang-Il; Yoshino, Fumihiko; Maruoka, Yutaka; Itoh, Toshiyuki; Ishikawa, Isao; Izumi, Yuichi

    2014-12-15

    Oral care is important for oral and systemic health, especially for elderly institutionalized individuals and compromised patients. However, conventional mechanical plaque control is often difficult for these patients because of the pain or the risk of aspiration. Although antimicrobial photodynamic therapy (aPDT), which is considered an alternative or adjunct to mechanical approaches, has potential application as a less stressful method of daily plaque control, no clinical application of this technique has been reported. We investigated the inhibitory effect of a combination of toluidine blue O (TBO), and a red light-emitting diode (LED) on dental plaque formation in healthy volunteers. The optimal concentration of TBO was determined in preliminary in vitro experiments to evaluate the bactericidal effect of aPDT on Streptococcus oralis and to clarify its safety in fibroblast cells. To survey the mechanism of TBO-mediated aPDT, the quality and quantity of reactive oxygen species (ROS) generated during aPDT were also examined using electron spin resonance (ESR) spectroscopy. Subsequently, the inhibitory effect of aPDT on dental plaque formation was investigated in eleven subjects as a clinical pilot study. The right or left mandibular premolars were randomly assigned to the treatment (with aPDT) or control (without aPDT) groups. In total, aPDT was applied six times (twice per day) to the teeth in the test group over a period of four days. On the fourth day, the study concluded and the analyses were performed. A combination of 500 or 1000 μg/ml TBO and LED irradiation for 20 s significantly decreased the number of colony forming units of Streptococcus oralis. The cytotoxicity of aPDT was comparable to that of standard antiseptics used in the oral cavity. Hydroxyl radicals were detected by ESR analysis, but singlet oxygen was not. A randomized controlled trial demonstrated that aPDT with 1000 μg/ml TBO and red LED irradiation significantly suppressed dental plaque

  3. Comparison of traditional cardiovascular risk models and coronary atherosclerotic plaque as detected by computed tomography for prediction of acute coronary syndrome in patients with acute chest pain.

    Science.gov (United States)

    Ferencik, Maros; Schlett, Christopher L; Bamberg, Fabian; Truong, Quynh A; Nichols, John H; Pena, Antonio J; Shapiro, Michael D; Rogers, Ian S; Seneviratne, Sujith; Parry, Blair Alden; Cury, Ricardo C; Brady, Thomas J; Brown, David F; Nagurney, John T; Hoffmann, Udo

    2012-08-01

    The objective was to determine the association of four clinical risk scores and coronary plaque burden as detected by computed tomography (CT) with the outcome of acute coronary syndrome (ACS) in patients with acute chest pain. The hypothesis was that the combination of risk scores and plaque burden improved the discriminatory capacity for the diagnosis of ACS. The study was a subanalysis of the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial-a prospective observational cohort study. The authors enrolled patients presenting to the emergency department (ED) with a chief complaint of acute chest pain, inconclusive initial evaluation (negative biomarkers, nondiagnostic electrocardiogram [ECG]), and no history of coronary artery disease (CAD). Patients underwent contrast-enhanced 64-multidetector-row cardiac CT and received standard clinical care (serial ECG, cardiac biomarkers, and subsequent diagnostic testing, such as exercise treadmill testing, nuclear stress perfusion imaging, and/or invasive coronary angiography), as deemed clinically appropriate. The clinical providers were blinded to CT results. The chest pain score was calculated and the results were dichotomized to ≥10 (high-risk) and patient was assigned to a low-, intermediate-, or high-risk category. Because of the low number of subjects in the high-risk group, the intermediate- and high-risk groups were combined into one. CT images were evaluated for the presence of plaque in 17 coronary segments. Plaque burden was stratified into none, intermediate, and high (zero, one to four, and more than four segments with plaque). An outcome panel of two physicians (blinded to CT findings) established the primary outcome of ACS (defined as either an acute myocardial infarction or unstable angina) during the index hospitalization (from the presentation to the ED to the discharge from the hospital). Logistic regression modeling was performed to examine the association of risk scores

  4. (18)F-FDG imaging of human atherosclerotic carotid plaques reflects gene expression of the key hypoxia marker HIF-1α

    DEFF Research Database (Denmark)

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

    2013-01-01

    To investigate the association between gene expression of key molecular markers of hypoxia and inflammation in atherosclerotic carotid lesions with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) uptake as determined clinically by positron emission tomography (PET). Studies using PET have demonstra......To investigate the association between gene expression of key molecular markers of hypoxia and inflammation in atherosclerotic carotid lesions with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) uptake as determined clinically by positron emission tomography (PET). Studies using PET have...... between hypoxia and glucose metabolism in vivo. The marker of inflammation CD68 is also associated with (18)F-FDG-uptake (SUVmax). As CD68 and HIF-1α gene expression co-variate their information is overlapping....

  5. Formation and maintenance of Alzheimer’s disease β-amyloid plaques in the absence of microglia

    Science.gov (United States)

    Grathwohl, Stefan A; Kälin, Roland E; Bolmont, Tristan; Prokop, Stefan; Winkelmann, Georg; Kaeser, Stephan A; Odenthal, Jörg; Radde, Rebecca; Eldh, Therese; Gandy, Sam; Aguzzi, Adriano; Staufenbiel, Matthias; Mathews, Paul M; Wolburg, Hartwig; Heppner, Frank L; Jucker, Mathias

    2016-01-01

    In Alzheimer’s disease, microglia cluster around β-amyloid deposits, suggesting that these cells are important for amyloid plaque formation, maintenance and/or clearance. We crossed two distinct APP transgenic mouse strains with CD11b-HSVTK mice, in which nearly complete ablation of microglia was achieved for up to 4 weeks after ganciclovir application. Neither amyloid plaque formation and maintenance nor amyloid-associated neuritic dystrophy depended on the presence of microglia. PMID:19838177

  6. Betel leaf toothpastes inhibit dental plaque formation on fixed orthodontic patients

    Directory of Open Access Journals (Sweden)

    Rizka Amelia Mayasari

    2011-12-01

    Full Text Available Background: Brackets, archwires, ligatures, and other fixed orthodontic appliance components complicate the use of conventional oral-hygiene measures. This often results in significant plaque accumulation around the bracket bases. The addition of betel leaf extract in toothpaste is expected to inhibit the growth of dental plaque. Purpose: The purpose of this study was to evaluate the effect of betel leaf toothpaste in inhibiting plaque formation on the fixed orthodontic patients. Methods: This study was done on dental student of Airlangga University aged 18–24 years, have been wearing fixed orthodontic appliances for 1–2 years, have no systemic diseases. The samples were divided into two groups, consisting of 20 samples. First group of samples brushed their teeth with betel group of samples brushed their teeth with betel brushed their teeth with betel leaf toothpaste and the second using placebo. The subjects were instructed to brush their teeth using Scrub method until reaching zero (0 scor of orthodontic plaque index (OPI. Plaque scores were taken again 4 hours after brushing. The statistical analysis was done by using paired t test. Results: The average of accumulated plaque on group that use betel leaf toothpaste was 25.54 and placebo was 41.09. The result showed that there was significant difference in plaque accumulation between the group with betel leaf toothpaste and placebo 4 hours after brushing (p = 0.001. Conclusion: In conclusion, betel leaf toothpaste is effective in inhibiting the dental plaque formation on the fixed orthodontic patients. Latar belakang: Bracket, kawat busur, kawat ligatur dan komponen peranti ortodonti cekat yang lain mempersulit pembersihan gigi secara konvensional. Hal ini sering menyebabkan terjadinya akumulasi plak di sekitar dasar braket. Penambahan ekstrak daun sirih yang mempunyai efek bakterisid pada pasta gigi diharapkan dapat menghambat pertumbuhan plak. Tujuan: Tujuan penelitian ini adalah untuk

  7. Plaque rupture in humans and mice

    DEFF Research Database (Denmark)

    Schwartz, Stephen M; Galis, Zorina S; Rosenfeld, Michael E

    2007-01-01

    Despite the many studies of murine atherosclerosis, we do not yet know the relevance of the natural history of this model to the final events precipitated by plaque disruption of human atherosclerotic lesions. The literature has become particularly confused because of the common use of terms...... such as "instability", "vulnerable", "rupture", or even "thrombosis" for features of plaques in murine model systems not yet shown to rupture spontaneously and in an animal surprisingly resistant to formation of thrombi at sites of atherosclerosis. We suggest that use of conclusory terms like "vulnerable" and "stable...... that various forms of data have implicated in plaque progression. For example, formation of the fibrous cap, protease activation, and cell death in the necrotic core can be well described and have all been modeled in well-defined experiments. The relevance of such well-defined, objective, descriptive...

  8. 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....

  9. 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...

  10. Geochemical patterns and microbial contribution to iron plaque formation in the rice plant rhizosphere

    Science.gov (United States)

    Maisch, Markus; Murata, Chihiro; Unger, Julia; Kappler, Andreas; Schmidt, Caroline

    2015-04-01

    Rice is the major food source for more than half of the world population and 80 percent of the worldwide rice cultivation is performed on water logged paddy soils. The establishment of reducing conditions in the soil and across the soil-water interface not only stimulates the microbial production and release of the greenhouse gas methane. These settings also create optimal conditions for microbial iron(III) reduction and therefore saturate the system with reduced ferrous iron. Through the reduction and dissolution of ferric minerals that are characterized by their high surface activity, sorbed nutrients and contaminants (e.g. arsenic) will be mobilized and are thus available for uptake by plants. Rice plants have evolved a strategy to release oxygen from their roots in order to prevent iron toxification in highly ferrous environments. The release of oxygen to the reduced paddy soil causes ferric iron plaque formation on the rice roots and finally increases the sorption capacity for toxic metals. To this date the geochemical and microbiological processes that control the formation of iron plaque are not deciphered. It has been hypothesized that iron(II)-oxidizing bacteria play a potential role in the iron(III) mineral formation along the roots. However, not much is known about the actual processes, mineral products, and geochemical gradients that establish within the rhizosphere. In the present study we have developed a growth set-up that allows the co-cultivation of rice plants and iron(II)-oxidizing bacteria, as well as the visual observation and in situ measurement of geochemical parameters. Oxygen and dissolved iron(II) gradients have been measured using microelectrodes and show geochemical hot spots that offer optimal growth conditions for microaerophilic iron(II) oxidizers. First mineral identification attempts of iron plaque have been performed using Mössbauer spectroscopy and microscopy. The obtained results on mineraology and crystallinity have been

  11. Patients with diabetes differ in atherosclerotic plaque characteristics and have worse clinical outcome after iliofemoral endarterectomy compared with patients without diabetes

    NARCIS (Netherlands)

    van Haelst, Steven T W; Haitjema, Saskia; de Vries, Jean Paul P M; Moll, Frans L.|info:eu-repo/dai/nl/070246882; Pasterkamp, Gerard|info:eu-repo/dai/nl/138488304; den Ruijter, Hester M.|info:eu-repo/dai/nl/304123846; de Borst, Gert J.|info:eu-repo/dai/nl/237108151

    OBJECTIVE: Diabetes mellitus (DM) is associated with peripheral arterial disease (PAD) and leads to worse clinical outcome compared with patients without DM. The objective of this study was to determine the impact of DM on iliofemoral artery plaque characteristics and to examine secondary clinical

  12. Attenuation of Apoptosis by Telmisartan in Atherosclerotic Plaques of Apolipoprotein E−/− Mice: Evaluation Using Technetium 99m–Annexin A5

    Directory of Open Access Journals (Sweden)

    Yan Zhao

    2013-07-01

    Full Text Available Technetium 99m (99mTc–annexin A5, a marker of ongoing apoptosis, is supposed to be useful in the detection of metabolically active atheroma. The aim of this study was to determine the potential of 99mTc–annexin A5 for evaluating the therapeutic effects of an angiotensin II receptor type 1 blocker (ARB (telmisartan on atherosclerosis. Male apolipoprotein E−/− mice were divided into telmisartan-treated (3 mg/kg/d, n = 10 and control (n = 10 groups. After 16 to 21 weeks of treatment, 99mTc–annexin A5 was injected and cryostat sections of aortic tissues (n = 10–12/aorta were prepared. The 99mTc–annexin A5 accumulation level in the plaques was evaluated by autoradiography. Serial sections of the plaques were histologically examined to identify the lesion phenotypes (normal vessels, early lesions, atheromatous lesions, and fibrotic lesions, plaque size, macrophage infiltration levels, and lipid deposition levels. Telmisartan treatment significantly decreased the plaque size (0.05 ± 0.05 vs 0.11 ± 0.08, mm2, macrophage infiltration level (0.02 ± 0.02 vs 0.03 ± 0.02, mm2, lipid deposition level (0.01 ± 0.01 vs 0.02 ± 0.02, mm2, and 99mTc–annexin A5 accumulation level (1.30 ± 1.09 vs 2.15 ± 1.91, × 10−6/g. 99mTc–annexin A5 accumulation levels in the plaques positively correlated with macrophage infiltration (r = .69, p < .05 and lipid deposition (r = .66, p < .05 levels. Apoptosis imaging with 99mTc–annexin A5 may be useful for evaluating the therapeutic effects of ARBs on atherosclerosis.

  13. Serum elastase activity, serum elastase inhibitors, and occurrence of carotid atherosclerotic plaques: the Etude sur le Vieillissement Artériel (EVA) study.

    Science.gov (United States)

    Zureik, Mahmoud; Robert, Ladislas; Courbon, Dominique; Touboul, Pierre-Jean; Bizbiz, Latifa; Ducimetière, Pierre

    2002-06-04

    In the last decades, interest has increased in the potential deleterious atherogenic effects of some cellular elastase activities. The results of experimental and clinical investigations were inconsistent. In this report, we assessed the associations of serum elastase activity and serum elastase inhibitors with carotid plaque occurrence during the 4-year follow-up in a population of 859 subjects free of coronary heart disease and stroke (age, 59 to 71 years). Serum elastase activity and serum elastase inhibitors were measured at baseline examination. Carotid B-mode ultrasound examination was performed at baseline and 2 years and 4 years later. The occurrence of carotid plaques in subjects with the lowest serum elastase activity values (quartile 1), in those with the intermediate values (quartiles 2 to 3), and in those with the highest values (quartile 4) was, respectively, 24.6%, 18.9%, and 12.2% (P<0.001 for trend). The multivariate odds ratios of carotid plaque occurrence associated with the three groups (adjusted for major known cardiovascular risk factors) were, respectively, 1.00, 0.67 (CI, 0.44 to 1.02; P<0.06), and 0.40 (CI, 0.23 to 0.70, P<0.001). For serum elastase inhibitors, the occurrence of carotid plaques in quartile 1 (lowest values), quartiles 2 to 3, and quartile 4 (highest values) was, respectively, 11.7%, 18.8%, and 25.2% (P for trend<0.001). The corresponding multivariate adjusted odds ratios were 1.00, 1.98 (CI, 1.19 to 3.31, P<0.01), and 3.18 (CI, 1.80 to 5.60, P<0.001). Low values of serum elastase activity and high values of serum elastase inhibitors were strongly and independently associated with increased 4-year carotid plaque occurrence. Further studies are necessary to elucidate the nature of the associations between elastase parameters and atherosclerosis.

  14. Validation of FDG uptake in the arterial wall as an imaging biomarker of atherosclerotic plaques with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT).

    Science.gov (United States)

    Bucci, Monica; Aparici, Carina Mari; Hawkins, Randy; Bacharach, Steve; Schrek, Carole; Cheng, Suchun; Tong, Elizabeth; Arora, Sandeep; Parati, Eugenio; Wintermark, Max

    2014-01-01

    From the literature, the prevalence of fluorodeoxyglucose (FDG) uptake in large artery atherosclerotic plaques shows great heterogeneity. We retrospectively reviewed 100 consecutive patients who underwent FDG-positron emission tomography-computed tomography (PET/CT) imaging of their whole body, to evaluate FDG uptake in the arterial wall. We retrospectively evaluated 100 whole-body PET-CT scans. The PET images coregistered with CT were reviewed for abnormal 18F-FDG uptake. The mean standard uptake value (SUV) was measured in regions of interest (ROIs). The prevalence of PET+ plaques was determined based on the qualitative PET review, used as the gold standard in a receiver-operating characteristic (ROC) curve analysis to determine an optimal threshold for the quantitative PET analysis. The qualitative, visual assessment demonstrated FDG uptake in the arterial walls of 26 patients. A total of 85 slices exhibited FDG uptake within the arterial wall of 37 artery locations. 11, 17, and 2 patients exhibited FDG uptake within the wall of carotid arteries, of the aorta, and of the iliac arteries, respectively. Only 4 of the 26 patients had positive FDG uptake in more than one artery location. In terms of quantitative analysis, a threshold of 2.8 SUV was associated with a negative predictive value of 99.4% and a positive predictive value of 100% to predict qualitative PET+ plaques. A threshold of 1.8 SUV was associated with a negative predictive value of 100% and a positive predictive value of 99.4%. Area under the ROC curve was .839. The prevalence of PET uptake in arterial walls in a consecutive population of asymptomatic patients is low and usually confined to one type of artery, and its clinical relevance in terms of vulnerability to ischemic events remains to be determined. Copyright © 2012 by the American Society of Neuroimaging.

  15. ArcR Modulates Biofilm Formation in the Dental Plaque Colonizer Streptococcus gordonii.

    Science.gov (United States)

    Robinson, Jill C; Rostami, Nadia; Casement, John; Vollmer, Waldemar; Rickard, Alexander H; Jakubovics, Nicholas S

    2017-11-15

    Biofilm formation and cell-cell sensing by the pioneer dental plaque coloniser Streptococcus gordonii is dependent upon arginine. This study aimed to identify genetic factors linking arginine-dependent responses and biofilm formation in S. gordonii. Isogenic mutants disrupted in genes required for biosynthesis or catabolism of arginine, or for arginine-dependent gene regulation, were screened for their ability to form biofilms in a static culture model. Biofilm formation by a knockout mutant of arcR, encoding an arginine-dependent regulator of transcription, was reduced to <50% that of the wild-type whereas other strains were unaffected. Complementation of S. gordonii ∆arcR with a plasmid-borne copy of arcR restored the ability to develop biofilms. By DNA microarray analysis, 25 genes were differentially regulated in S. gordonii ∆arcR compared with wild-type under arginine-replete conditions including 8 genes encoding components of phosphotransferase systems for sugar uptake. By contrast, disruption of argR or ahrC genes, which encode paralogous arginine-dependent regulators, each resulted in significant changes in the expression of more than 100 genes. Disruption of a gene encoding a putative extracellular protein that was strongly regulated in S. gordonii ∆arcR had a minor impact on biofilm formation. We hypothesise that genes regulated by ArcR form a critical pathway linking arginine sensing to biofilm formation in S. gordonii. Further elucidation of this pathway may provide new targets for the control of dental plaque formation by inhibiting biofilm formation by a key pioneer coloniser of tooth surfaces. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Omentin attenuates atherosclerotic lesion formation in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Hiramatsu-Ito, Mizuho; Shibata, Rei; Ohashi, Koji; Uemura, Yusuke; Kanemura, Noriyoshi; Kambara, Takahiro; Enomoto, Takashi; Yuasa, Daisuke; Matsuo, Kazuhiro; Ito, Masanori; Hayakawa, Satoko; Ogawa, Hayato; Otaka, Naoya; Kihara, Shinji; Murohara, Toyoaki; Ouchi, Noriyuki

    2016-05-01

    Obesity is associated with the development of atherosclerosis. We previously demonstrated that omentin is a circulating adipokine that is downregulated in association with atherosclerotic diseases. Here, we examined the impact of omentin on the development of atherosclerosis with gain-of-function genetic manipulations and dissected its potential mechanism. Apolipoprotein E-deficient (apoE-KO) mice were crossed with transgenic mice expressing the human omentin gene (OMT-Tg) mice in fat tissue to generate apoE-KO/OMT-Tg mice. ApoE-KO/OMT-Tg mice exhibited a significant reduction of the atherosclerotic areas in aortic sinus, compared with apoE-KO mice despite similar lipid levels. ApoE-KO/OMT-Tg mice also displayed significant decreases in macrophage accumulation and mRNA expression of proinflammatory mediators including tumour necrosis factor-α, interleukin-6, and monocyte chemotactic protein-1 in aorta when compared with apoE-KO mice. Treatment of human monocyte-derived macrophages with a physiological concentration of human omentin protein led to reduction of lipid droplets and cholesteryl ester content. Treatment with human omentin protein also reduced lipopolysaccharide-induced expression of proinflammatory genes in human macrophages. Treatment of human macrophages with omentin promoted the phosphorylation of Akt. Inhibition of Akt signalling abolished the anti-inflammatory actions of omentin in macrophages. These data document for the first time that omentin reduces the development of atherosclerosis by reducing inflammatory response of macrophages through the Akt-dependent mechanisms. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  17. Cytopathic effect and plaque formation by arboviruses in a continuous cell line (XTC-2) from the toad Xenopus laevis.

    Science.gov (United States)

    Leake, C J; Varma, M G; Pudney, M

    1977-05-01

    Forty-six arboviruses were tested for c.p.e. and/or plaque formation in an amphibian cell line. C.p.e. was observed with a high proportion of the viruses tested. Comparative plaque assay, in the XTC-2 cells at 28 degrees C and Vero cells at 37 degrees C, suggests that these systems are comparable in sensitivity and susceptibility to infection. Practical uses of this cell line are discussed.

  18. Cross-Linking GPVI-Fc by Anti-Fc Antibodies Potentiates Its Inhibition of Atherosclerotic Plaque- and Collagen-Induced Platelet Activation

    Directory of Open Access Journals (Sweden)

    Janina Jamasbi, RPh

    2016-04-01

    Full Text Available To enhance the antithrombotic properties of recombinant glycoprotein VI fragment crystallizable (GPVI-Fc, the authors incubated GPVI-Fc with anti-human Fc antibodies to cross-link the Fc tails of GPVI-Fc. Cross-linking potentiated the inhibition of human plaque- and collagen-induced platelet aggregation by GPVI-Fc under static and flow conditions without increasing bleeding time in vitro. Cross-linking with anti-human-Fc Fab2 was even superior to anti-human-Fc immunoglobulin G (IgG. Advanced optical imaging revealed a continuous sheath-like coverage of collagen fibers by cross-linked GPVI-Fc complexes. Cross-linking of GPVI into oligomeric complexes provides a new, highly effective, and probably safe antithrombotic treatment as it suppresses platelet GPVI-plaque interaction selectively at the site of acute atherothrombosis.

  19. Data on consistency among different methods to assess atherosclerotic plaque echogenicity on standard ultrasound and intraplaque neovascularization on contrast-enhanced ultrasound imaging in human carotid artery

    Directory of Open Access Journals (Sweden)

    Mattia Cattaneo

    2016-12-01

    Full Text Available Here we provide the correlation among different carotid ultrasound (US variables to assess echogenicity n standard carotid US and to assess intraplaque neovascularization on contrast enhanced US. We recruited 45 consecutive subjects with an asymptomatic≥50% carotid artery stenosis. Carotid plaque echogenicity at standard US was visually graded according to Gray–Weale classification (GW and measured by the greyscale median (GSM, a semi-automated computerized measurement performed by Adobe Photoshop®. On CEUS imaging IPNV was graded according to the visual appearance of contrast within the plaque according to three different methods: CEUS_A (1=absent; 2=present; CEUS_B a three-point scale (increasing IPNV from 1 to 3; CEUS_C a four-point scale (increasing IPNV from 0 to 3. We have also implemented a new simple quantification method derived from region of interest (ROI signal intensity ratio as assessed by QLAB software. Further information is available in “Contrast-enhanced ultrasound imaging of intraplaque neovascularization and its correlation to plaque echogenicity in human carotid arteries atherosclerosis (M. Cattaneo, D. Staub, A.P. Porretta, J.M. Gallino, P. Santini, C. Limoni et al., 2016 [1].

  20. Moderate Autophagy Inhibits Vascular Smooth Muscle Cell Senescence to Stabilize Progressed Atherosclerotic Plaque via the mTORC1/ULK1/ATG13 Signal Pathway

    Directory of Open Access Journals (Sweden)

    Zhenli Luo

    2017-01-01

    Full Text Available In order to investigate the effects of autophagy induced by rapamycin in the development of atherosclerosis plaque we established murine atherosclerosis model which was induced in ApoE−/− mice by high fat and cholesterol diet (HFD for 16 weeks. Rapamycin and 3-Methyladenine (MA were used as autophagy inducer and inhibitor respectively. The plaque areas in aortic artery were detected with HE and Oil Red O staining. Immunohistochemical staining were applied to investigate content of plaque respectively. In contrast to control and 3-MA groups, rapamycin could inhibit atherosclerosis progression. Rapamycin was able to increase collagen content and a-SMA distribution relatively, as well as decrease necrotic core area. Then we used MOVAS and culture with ox-LDL for 72 h to induce smooth muscle-derived foam cell model in vitro. Rapamycin and 3-MA were cultured together respectively. Flow cytometry assay and SA-β-Gal staining experiments were performed to detect survival and senescence of VSMCs. Western blot analysis were utilized to analyze the levels of protein expression. We found that rapamycin could promote ox-LDL-induced VSMCs autophagy survival and alleviate cellular senescence, in comparison to control and 3-MA groups. Western blot analysis showed that rapamycin could upregulate ULK1, ATG13 and downregulate mTORC1 and p53 protein expression.

  1. Eicosapentaenoic acid reduces membrane fluidity, inhibits cholesterol domain formation, and normalizes bilayer width in atherosclerotic-like model membranes.

    Science.gov (United States)

    Mason, R Preston; Jacob, Robert F; Shrivastava, Sandeep; Sherratt, Samuel C R; Chattopadhyay, Amitabha

    2016-12-01

    Cholesterol crystalline domains characterize atherosclerotic membranes, altering vascular signaling and function. Omega-3 fatty acids reduce membrane lipid peroxidation and subsequent cholesterol domain formation. We evaluated non-peroxidation-mediated effects of eicosapentaenoic acid (EPA), other TG-lowering agents, docosahexaenoic acid (DHA), and other long-chain fatty acids on membrane fluidity, bilayer width, and cholesterol domain formation in model membranes. In membranes prepared at 1.5:1 cholesterol-to-phospholipid (C/P) mole ratio (creating pre-existing domains), EPA, glycyrrhizin, arachidonic acid, and alpha linolenic acid promoted the greatest reductions in cholesterol domains (by 65.5%, 54.9%, 46.8%, and 45.2%, respectively) compared to controls; other treatments had modest effects. EPA effects on cholesterol domain formation were dose-dependent. In membranes with 1:1 C/P (predisposing domain formation), DHA, but not EPA, dose-dependently increased membrane fluidity. DHA also induced cholesterol domain formation without affecting temperature-induced changes in-bilayer unit cell periodicity relative to controls (d-space; 57Å-55Å over 15-30°C). Together, these data suggest simultaneous formation of distinct cholesterol-rich ordered domains and cholesterol-poor disordered domains in the presence of DHA. By contrast, EPA had no effect on cholesterol domain formation and produced larger d-space values relative to controls (60Å-57Å; pmembrane bilayer width, membrane fluidity, and cholesterol crystalline domain formation; suggesting omega-3 fatty acids with differing chain length or unsaturation may differentially influence membrane lipid dynamics and structural organization as a result of distinct phospholipid/sterol interactions. Copyright © 2016. Published by Elsevier B.V.

  2. On the potential of a new IVUS elasticity modulus imaging approach for detecting vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study.

    Science.gov (United States)

    Le Floc'h, Simon; Cloutier, Guy; Finet, Gérard; Tracqui, Philippe; Pettigrew, Roderic I; Ohayon, Jacques

    2010-10-07

    Peak cap stress amplitude is recognized as a good indicator of vulnerable plaque (VP) rupture. However, such stress evaluation strongly relies on a precise, but still lacking, knowledge of the mechanical properties exhibited by the plaque components. As a first response to this limitation, our group recently developed, in a previous theoretical study, an original approach, called iMOD (imaging modulography), which reconstructs elasticity maps (or modulograms) of atheroma plaques from the estimation of strain fields. In the present in vitro experimental study, conducted on polyvinyl alcohol cryogel arterial phantoms, we investigate the benefit of coupling the iMOD procedure with the acquisition of intravascular ultrasound (IVUS) measurements for detection of VP. Our results show that the combined iMOD-IVUS strategy: (1) successfully detected and quantified soft inclusion contours with high positive predictive and sensitivity values of 89.7 ± 3.9% and 81.5 ± 8.8%, respectively, (2) estimated reasonably cap thicknesses larger than ∼300 µm, but underestimated thinner caps, and (3) quantified satisfactorily Young's modulus of hard medium (mean value of 109.7 ± 23.7 kPa instead of 145.4 ± 31.8 kPa), but overestimated the stiffness of soft inclusions (mean Young`s moduli of 31.4 ± 9.7 kPa instead of 17.6 ± 3.4 kPa). All together, these results demonstrate a promising benefit of the new iMOD-IVUS clinical imaging method for in vivo VP detection.

  3. On the potential of a new IVUS elasticity modulus imaging approach for detecting vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study

    Energy Technology Data Exchange (ETDEWEB)

    Floc' h, Simon Le; Tracqui, Philippe; Ohayon, Jacques [Laboratory TIMC-DynaCell, UJF, CNRS UMR 5525, In3S, Grenoble (France); Cloutier, Guy [Laboratory of Biorheology and Medical Ultrasonics, Research Center, University of Montreal Hospital (CRCHUM), Montreal, Quebec (Canada); Finet, Gerard [Department of Hemodynamics and Interventional Cardiology, Hospices Civils de Lyon and Claude Bernard University Lyon 1, INSERM Unit 886, Lyon (France); Pettigrew, Roderic I, E-mail: Guy.Cloutier@umontreal.c, E-mail: Jacques.Ohayon@imag.f [Laboratory of Integrative Cardiovascular Imaging Science, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States)

    2010-10-07

    Peak cap stress amplitude is recognized as a good indicator of vulnerable plaque (VP) rupture. However, such stress evaluation strongly relies on a precise, but still lacking, knowledge of the mechanical properties exhibited by the plaque components. As a first response to this limitation, our group recently developed, in a previous theoretical study, an original approach, called iMOD (imaging modulography), which reconstructs elasticity maps (or modulograms) of atheroma plaques from the estimation of strain fields. In the present in vitro experimental study, conducted on polyvinyl alcohol cryogel arterial phantoms, we investigate the benefit of coupling the iMOD procedure with the acquisition of intravascular ultrasound (IVUS) measurements for detection of VP. Our results show that the combined iMOD-IVUS strategy: (1) successfully detected and quantified soft inclusion contours with high positive predictive and sensitivity values of 89.7 {+-} 3.9% and 81.5 {+-} 8.8%, respectively, (2) estimated reasonably cap thicknesses larger than {approx}300 {mu}m, but underestimated thinner caps, and (3) quantified satisfactorily Young's modulus of hard medium (mean value of 109.7 {+-} 23.7 kPa instead of 145.4 {+-} 31.8 kPa), but overestimated the stiffness of soft inclusions (mean Young's moduli of 31.4 {+-} 9.7 kPa instead of 17.6 {+-} 3.4 kPa). All together, these results demonstrate a promising benefit of the new iMOD-IVUS clinical imaging method for in vivo VP detection.

  4. The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE(-/-) mice

    DEFF Research Database (Denmark)

    Kim, Christine H. J.; Mitchell, James B.; Bursill, Christina A.

    2015-01-01

    cholesterol, inflammatory cytokines and markers (interleukin-6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase, MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells. RESULTS: High...... fat feeding resulted in marked increases in body mass and plasma lipid levels. Dietary TEMPOL decreased both parameters. In the high-fat-fed mice significant elevations in plasma lipid levels and the inflammatory markers IL-6, MCP-1, MPO, SAA were detected, along with an increase in leptin...

  5. Quantification of temporal changes in calcium score in active atherosclerotic plaque in major vessels by {sup 18}F-sodium fluoride PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Yoshinobu; Kaneta, Tomohiro; Nawata, Shintaro; Hino-Shishikura, Ayako; Yoshida, Keisuke; Inoue, Tomio [Yokohama City University, Graduate School of Medicine, Department of Radiology, Yokohama, Kanagawa (Japan)

    2017-08-15

    Our aim was to assess whether {sup 18}F-NaF PET/CT is able to predict progression of the CT calcium score. Between August 2007 and November 2015, 34 patients (18 women, 16 men; age, mean ± standard deviation, 57.5 ± 13.9 years; age range 19-78 years) with malignancy or orthopaedic disease were enrolled in this study, with approximately 1-year follow-up data. Baseline and follow-up CT images were retrospectively evaluated for the presence of calcification sites in major vessel walls. The maximum and mean CT values (CTmax and CTmean, in Hounsfield units), calcification volumetric score (CVS, in cubic millimetres) and Agatston units score (AU) were evaluated for each site. Subsequent changes in CTmax, CTmean, CVS and AU were calculated and expressed as ΔCTmax, ΔCTmean, ΔCVS and ΔAU, respectively. We then evaluated the relationship between {sup 18}F-NaF uptake (using the maximum target-to-background ratio, TBRmax, and the maximum blood-subtracted {sup 18}F-NaF activity, bsNaFmax, which was obtained by subtracting the SUVmax of each calcified plaque lesion and NaF-avid site from the SUVmean in the right atrium blood pool) and the change in calcified plaque volume and characteristics obtained after 1 year. We detected and analysed 182 calcified plaque sites and 96 hot spots on major vessel walls. {sup 18}F-NaF uptake showed very weak correlations with CTmax, CTmean, CVS, CVS after 1 year, AU and AU after 1 year on both baseline and follow-up PET/CT scans for each site. {sup 18}F-NaF uptake showed no correlation with ΔCTmax or ΔCTmean. However, there was a significant correlation between the intensity of {sup 18}F-NaF uptake and ΔCVS and ΔAU. {sup 18}F-NaF uptake has a strong correlation with calcium score progression which was a predictor of future cardiovascular disease risk. PET/CT using {sup 18}F-NaF may be able to predict calcium score progression which is known to be the major characteristic of atherosclerosis. (orig.)

  6. Multispectral optoacoustic tomography resolves smart probe activation in vulnerable plaques

    Science.gov (United States)

    Razansky, Daniel; Harlaar, Niels J.; Hillebrands, Jan-Luuk; Taruttis, Adrian; Herzog, Eva; Zeebregts, Clark; van Dam, Goitzen; Ntziachristos, Vasilis

    2011-03-01

    In this work, we show, for the first time to our knowledge, that multispectral optoacoustic tomography (MSOT) can deliver high resolution images of activatable molecular probe's distribution, sensitive to matrix metalloproteinases (MMP), deep within optically scattering human carotid specimen. It is further demonstrated that this method can be used in order to provide accurate maps of vulnerable plaque formations in atherosclerotic disease. Moreover, optoacoustic images can simultaneously show the underlining plaque morphology for accurate localization of MMP activity in three dimensions. This performance directly relates to small animal screening applications and to clinical potential as well.

  7. High-speed intravascular photoacoustic imaging of lipid-laden atherosclerotic plaque enabled by a 2-kHz barium nitrite raman laser.

    Science.gov (United States)

    Wang, Pu; Ma, Teng; Slipchenko, Mikhail N; Liang, Shanshan; Hui, Jie; Shung, K Kirk; Roy, Sukesh; Sturek, Michael; Zhou, Qifa; Chen, Zhongping; Cheng, Ji-Xin

    2014-11-04

    Lipid deposition inside the arterial wall is a key indicator of plaque vulnerability. An intravascular photoacoustic (IVPA) catheter is considered a promising device for quantifying the amount of lipid inside the arterial wall. Thus far, IVPA systems suffered from slow imaging speed (~50 s per frame) due to the lack of a suitable laser source for high-speed excitation of molecular overtone vibrations. Here, we report an improvement in IVPA imaging speed by two orders of magnitude, to 1.0 s per frame, enabled by a custom-built, 2-kHz master oscillator power amplifier (MOPA)-pumped, barium nitrite [Ba(NO3)2] Raman laser. This advancement narrows the gap in translating the IVPA technology to the clinical setting.

  8. Accuracy of statin assignment using the 2013 AHA/ACC Cholesterol Guideline versus the 2001 NCEP ATP III guideline: correlation with atherosclerotic plaque imaging.

    Science.gov (United States)

    Johnson, Kevin M; Dowe, David A

    2014-09-02

    Accurate assignment of statin therapy is a major public health issue. The American Heart Association and the American College of Cardiology released a new guideline on the assessment of cardiovascular risk (GACR) to replace the 2001 National Cholesterol Education Program (NCEP) Adult Treatment Panel III recommendations. The aim of this study was to determine which method more accurately assigns statins to patients with features of coronary imaging known to have predictive value for cardiovascular events and whether more patients would be assigned to statins under the new method. The burden of coronary atherosclerosis on computed tomography angiography was measured in several ways on the basis of a 16-segment model. Whether to assign a given patient to statin therapy was compared between the NCEP and GACR guidelines. A total of 3,076 subjects were studied (65.3% men, mean age 55.4 ± 10.3 years, mean age of women 58.9 ± 10.3 years). The probability of prescribing statins rose sharply with increasing plaque burden under the GACR compared with the NCEP guideline. Under the NCEP guideline, 59% of patients with ≥50% stenosis of the left main coronary artery and 40% of patients with ≥50% stenosis of other branches would not have been treated. The comparable results for the GACR were 19% and 10%. The use of low-density lipoprotein targets seriously degraded the accuracy of the NCEP guideline for statin assignment. The proportion of patients assigned to statin therapy was 15% higher under the GACR. The new American Heart Association/American College of Cardiology guideline matches statin assignment to total plaque burden better than the older guidelines, with only a modest increase in the number of patients who were assigned statins. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Blood pressure reverse-dipping is associated with early formation of carotid plaque in senior hypertensive patients.

    Science.gov (United States)

    Yan, Bin; Peng, Liyuan; Han, Donggang; Sun, Lu; Dong, Quan; Yang, Pengtao; Zheng, Fengwei; Ong, HeanYee; Zeng, Lingfang; Wang, Gang

    2015-03-01

    Nocturnal variations in blood pressure (BP) were associated with carotid intima-media thickness. However, the precise relationship between circadian variations of BP and carotid plaques remains unknown. Therefore, the prognostic value of reverse-dipper pattern of BP for carotid plaque was investigated. In this cross-sectional study, a total of 524 hypertensive patients were recruited and evaluated with ambulatory BP monitoring between April 2012 and June 2013. Carotid plaque was classified into Grade 0 (normal or no observable plaque), Grade 1 (mild stenosis, 1%-24% narrowing), and Grade 2 (moderate stenosis, ≥25% narrowing). Multinomial logistic regression was applied to analyze the relationship between different degrees of carotid plaque and ambulatory BP monitoring results. Reverse-dipper pattern of BP was more common in older patients, smokers, and those with elevated fasting glucose. The incidences of coronary artery disease, lacunar infarction, and diabetes were also higher among hypertensive with reverse-dipper pattern. Multinomial logistic regression analysis showed that reverse dipper (odds ratio [OR] 2.500; 95% confidence interval [CI] 1.320-4.736; P = 0.005), age (OR 1.089; 95% CI 1.067-1.111; P reverse-dipper pattern of BP (2.308; 95% CI 1.223-4.355; P = 0.010). Reverse-dipper pattern of BP may be a risk factor for carotid atherosclerosis and play a crucial role in the early formation of carotid plaque.

  10. Comparing the three color pounehh tooth paste with the conventional one in preventing the formation of the microbial plaque

    Directory of Open Access Journals (Sweden)

    Ebadifar A.

    2008-11-01

    Full Text Available "nBackground and Aim: Plaque control has always been important in preventive dentistry. Various methods and materials have been introduced for this purpose. Recently a three-colored tooth paste has been introduced which claims to prevent plaque formation. The aim of this study was to compare three-colored pouneh tooth paste containing triclosan with the conventional one in preventing plaque formation. "nMaterials and Methods: This was a randomized double blind cross over clinical trial which was carried out on 40 dental students of Tehran azad university in 2005. Before beginning the trial, the index of plaque was evaluated, registered and reduced to null. The subjects were randomly divided into two groups, the case group (three color tooth paste and the control group (conventional tooth paste. The participants were asked to apply the specified tooth paste with an oral B Advantage Artica toothbrush for two weeks. After two weeks, the amount of plaque was re-registered and again reduced to null. The type of tooth paste was changed among two groups and the plaque was registered for the third time at the end of two weeks. Then the patients and assessors were not aware of the type of tooth paste in the tubes (double blind. McNamar and ManWhitney test were used. "nResults: From the 40 subjects, 4 cases were omitted due to the different reasons. The amount of initial plaque index was 88.3 12.1 which was reduced to 78.2 16.9 in the control and 74.1 19.3 in the case group. The difference between primary plaque and secondary plaque (after applying tooth paste was significant in both case and control groups, however there was not any significant difference between two groups. "nConclusion: Based on the results of this study, there was not any significant difference between conventional and three-colored tooth paste in reducing the plaque index.

  11. The clinical value of histological femoral artery plaque analysis

    NARCIS (Netherlands)

    Derksen, W.J.M.

    2011-01-01

    This thesis showed that the dissected femoral atherosclerotic plaque contains a predictive value for clinical outcome after femoral endarterectomy. Plaque histology analysis should be incorporated in clinical practice to help predict the patient at risk for restenosis or secondary cardiovascular

  12. Image Analysis for Contrast Enhanced Ultrasound Carotid Plaque Imaging

    NARCIS (Netherlands)

    Z. Akkus (Zeynettin)

    2014-01-01

    markdownabstract__Abstract__ Intraplaque neovascularization (IPN) has been presented as an important biomarker for progressive atherosclerotic disease and plaque vulnerability in several pathological studies. Therefore, quantification of IPN may allow early prediction of plaque at risk of rupture

  13. Study of the evolution of aortic atherosclerotic inflammatory plaques using {sup 18}F-FDG PET/CT; Evolution temporelle des foyers inflammatoires d'atherome aortique avec le morphoTEP au {sup 18}F-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Bertrand, A.C.; Netter, F.; Muller, M.A.; Djaballah, W.; Bruna, C.; Olivier, P.; Karcher, G.; Marie, P.Y. [Centre Hospitalier Universitaire, Service de Medecine Nucleaire, 54 - Nancy (France)

    2006-02-15

    PET allows focal uptake of {sup 18}F-FDG to be identified on aortic walls, and these foci might be linked to inflammatory atherosclerotic plaques. The goal of our study was to determine the temporal evolution of these foci. Material and methods: Twenty eight patients undergoing two {sup 18}F-FDG PET/CT within a two month period (1.5{+-}0.5 months on average), were considered. {sup 18}F-FDG uptakes were visually detected on thoracic aorta walls and the maximum activity level of these foci was expressed by a ratio with blood aortic activity (W/B). Results: 35 parietal aortic foci were detected on the initial PET/CT among which 26 were still detected on the second PET/CT together with 5 new foci; therefore the agreement rate between the two examinations was 65% for the visual detection of parietal aortic foci. The ratio W/B was 1.48{+-}0.22 on average. Between the two examinations the evolution of the W/B ratio was only correlated to the initial activity (p=0.02), mainly because the most active foci (W/B>1.6) had a marked activity decrease. Conclusion: When 2 different PET/CT are carried out on the same patients within lower than a two month period, activity from parietal aortic foci seems generally stable, with a concordance rate of 65% between the 2 investigations, and this might relate to a chronic mode of the evolution of inflammation and atherosclerosis. A further decrease in activity was, however, consistently documented for the foci showing the highest activity at baseline, and this might relate to a more evolutive and acute inflammatory process. (author)

  14. The effect of silicon on iron plaque formation and arsenic accumulation in rice genotypes with different radial oxygen loss (ROL).

    Science.gov (United States)

    Wu, Chuan; Zou, Qi; Xue, Sheng-Guo; Pan, Wei-Song; Huang, Liu; Hartley, William; Mo, Jing-Yu; Wong, Ming-Hung

    2016-05-01

    Rice is one of the major pathways of arsenic (As) exposure in human food chain, threatening over half of the global population. Greenhouse pot experiments were conducted to examine the effects of Si application on iron (Fe) plaque formation, As uptake and rice grain As speciation in indica and hybrid rice genotypes with different radial oxygen loss (ROL) ability. The results demonstrated that Si significantly increased root and grain biomass. Indica genotypes with higher ROL induced greater Fe plaque formation, compared to hybrid genotypes and sequestered more As in Fe plaque. Silicon applications significantly increased Fe concentrations in iron plaque of different genotypes, but it decreased As concentrations in the roots, straws and husks by 28-35%, 15-35% and 32-57% respectively. In addition, it significantly reduced DMA accumulation in rice grains but not inorganic As accumulation. Rice of indica genotypes with higher ROL accumulated lower concentrations of inorganic As in grains than hybrid genotypes with lower ROL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Nonspecific Factors in Monkey Tissues and Serum Causing Inhibition of Plaque Formation and Hemagglutination by Dengue Viruses

    Science.gov (United States)

    Nash, Donald R.; Halstead, Scott B.; Stenhouse, Andrew C.; McCue, Carolyn

    1971-01-01

    Normal monkey serum and the supernatant fluid from different triturated monkey tissues have been studied for the presence of nonspecific arbovirus hemagglutination and plaque forming inhibitors of dengue viruses types 1, 2, 3, and 4. Hemagglutination inhibition (HI) activity was present in most tissue specimens and demonstrated a significant gradient of effectiveness starting with, respectively, serum, spleen, adrenal, and lung having a high degree of activity, whereas skin, heart, muscle, brain, and liver demonstrated low HI titers. A slightly reversed gradient of effectiveness was obtained for the case of dengue virus inhibition of plaque formation with bile, liver, thymus, spleen, and adrenal giving high 50% plaque reduction titers and heart, muscle, serum, skin, and fat demonstrating little or no activity. Analysis by Sephadex G-200 chromatography and sucrose density gradient centrifugation suggests that HI and plaque formation inhibition are independent activities of normal serum or tissue constituents or both. Also, in addition to the physical methods of characterization, chemical treatment by absorption with kaolin or acetone extraction indicate both phenomena to be the result of the action of lipids or lipoproteins. PMID:16557953

  16. Inhibition of Cariogenic Plaque Formation on Root Surface with Polydopamine-Induced-Polyethylene Glycol Coating

    Directory of Open Access Journals (Sweden)

    May Lei Mei

    2016-05-01

    Full Text Available Root caries prevention has been a challenge for clinicians due to its special anatomical location, which favors the accumulation of dental plaque. Researchers are looking for anti-biofouling material to inhibit bacterial growth on exposed root surfaces. This study aimed to develop polydopamine-induced-polyethylene glycol (PEG and to study its anti-biofouling effect against a multi-species cariogenic biofilm on the root dentine surface. Hydroxyapatite disks and human dentine blocks were divided into four groups for experiments. They received polydopamine-induced-PEG, PEG, polydopamine, or water application. Contact angle, quartz crystal microbalance, and Fourier transform infrared spectroscopy were used to study the wetting property, surface affinity, and an infrared spectrum; the results indicated that PEG was induced by polydopamine onto a hydroxyapatite disk. Salivary mucin absorption on hydroxyapatite disks with polydopamine-induced-PEG was confirmed using spectrophotometry. The growth of a multi-species cariogenic biofilm on dentine blocks with polydopamine-induced-PEG was assessed and monitored by colony-forming units, confocal laser scanning microscopy, and scanning electron microscopy. The results showed that dentine with polydopamine-induced-PEG had fewer bacteria than other groups. In conclusion, a novel polydopamine-induced-PEG coating was developed. Its anti-biofouling effect inhibited salivary mucin absorption and cariogenic biofilm formation on dentine surface and thus may be used for the prevention of root dentine caries.

  17. Inhibition of Cariogenic Plaque Formation on Root Surface with Polydopamine-Induced-Polyethylene Glycol Coating.

    Science.gov (United States)

    Mei, May Lei; Li, Quan-Li; Chu, Chun Hung

    2016-05-25

    Root caries prevention has been a challenge for clinicians due to its special anatomical location, which favors the accumulation of dental plaque. Researchers are looking for anti-biofouling material to inhibit bacterial growth on exposed root surfaces. This study aimed to develop polydopamine-induced-polyethylene glycol (PEG) and to study its anti-biofouling effect against a multi-species cariogenic biofilm on the root dentine surface. Hydroxyapatite disks and human dentine blocks were divided into four groups for experiments. They received polydopamine-induced-PEG, PEG, polydopamine, or water application. Contact angle, quartz crystal microbalance, and Fourier transform infrared spectroscopy were used to study the wetting property, surface affinity, and an infrared spectrum; the results indicated that PEG was induced by polydopamine onto a hydroxyapatite disk. Salivary mucin absorption on hydroxyapatite disks with polydopamine-induced-PEG was confirmed using spectrophotometry. The growth of a multi-species cariogenic biofilm on dentine blocks with polydopamine-induced-PEG was assessed and monitored by colony-forming units, confocal laser scanning microscopy, and scanning electron microscopy. The results showed that dentine with polydopamine-induced-PEG had fewer bacteria than other groups. In conclusion, a novel polydopamine-induced-PEG coating was developed. Its anti-biofouling effect inhibited salivary mucin absorption and cariogenic biofilm formation on dentine surface and thus may be used for the prevention of root dentine caries.

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

    Science.gov (United States)

    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.

  19. In vitro screening of Chinese medicinal toothpastes: their effects on growth and plaque formation of mutans streptococci.

    Science.gov (United States)

    Wu-Yuan, C D; Green, L; Birch, W X

    1990-01-01

    Many plant extracts or derivatives have been incorporated into commercial toothpastes to treat oral diseases related to caries or periodontal diseases in China. However, no information is available concerning their in vitro effects on oral bacteria. Thirty-one Chinese medicinal toothpastes were selected for this study. Their ability to inhibit growth, in vitro plaque formation and glucosyltransferase (GTF) activity of Streptococcus sobrinus B13 and Streptococcus mutans 3209 were examined. Eighty-seven percent of the tested toothpastes inhibited the growth of the mutans streptococci, with zones ranging from 0.8 to 2.5 cm. At 10 mg/ml, 74% of the toothpastes inhibited in vitro plaque formation by S. mutans. Among these, 60% completely suppressed water-insoluble glucan synthesis from sucrose by GTF. Based on data obtained from our study, the incorporation of natural plant products or their derivatives into dentifrices seems a feasible means of promoting oral health and controlling dental diseases.

  20. The influence of xylitol containing toothpaste on plaque formation inhibition on fixed bridge

    OpenAIRE

    Fithrony, Hamim; Djulaeha, Eha; Soedjono, Michel

    2009-01-01

    Background: Plaque is the main cause of teeth and periodontal tissue damage, which usually accumulates on crown surfaces. To avoid this, plaque control is the best way that not only has a close connection to oral hygiene but also become important element in dental practice. Previously, xylitol was used as alternative sweetener for diabetic patients, but later it is used to maintain healthy teeth. Xylitol is capable to inhibit Streptococcus mutans growth which changes sugar and other carbohydr...

  1. Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial.

    Science.gov (United States)

    Amrutesh, Sunita; Malini, J; Tandur, Prakash S; Patki, Pralhad S

    2010-01-01

    The aim of this study was to evaluate the efficacy and safety of herbal dental cream in comparison to fluoride dental cream. Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial. One hundred and two patients with established dental plaque were randomly assigned to either herbal dental group or fluoride dental group for six weeks in a double-blind design. Improvement in plaque index, oral hygiene status, bleeding index, and gingival index was evaluated in these patients along with microbiological study. Results indicated a significant reduction in plaque index, gingival index, oral hygiene index, and microbial growth in both groups. Difference between the groups was not significant. There was no significant change in bleeding index. No adverse events were reported and both the dental creams were well tolerated. The finding of this preliminary study indicates that herbal dental cream is as safe and effective as fluoride dental cream, but not superior to it.

  2. Imaging the event-prone coronary artery plaque.

    Science.gov (United States)

    Giannopoulos, Andreas A; Benz, Dominik C; Gräni, Christoph; Buechel, Ronny R

    2017-07-06

    Acute coronary events, the dreaded manifestation of coronary atherosclerosis, remain one of the main contributors to mortality and disability in the developed world. The majority of those events are associated with atherosclerotic plaques-related thrombus formation following an acute disruption, that being rupture or erosion, of an event-prone lesion. These historically termed vulnerable plaques have been the target of numerous benchtop and clinical research endeavors, yet to date without solid results that would allow for early identification and potential treatment. Technological leaps in cardiovascular imaging have provided novel insights into the formation and role of the event-prone plaques. From intracoronary optical coherence tomography that has enhanced our understanding of the pathophysiological mechanisms of plaque disruption, over coronary computed tomography angiography that enables non-invasive serial plaque imaging, and positron emission tomography poised to be rapidly implemented into clinical practice to the budding field of plaque imaging with cardiac magnetic resonance, we summarize the invasive and non-invasive imaging modalities currently available in our armamentarium. Finally, the current status and potential future imaging directions are critically appraised.

  3. 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

  4. A randomized clinical study for comparative evaluation of Aloe Vera and 0.2% chlorhexidine gluconate mouthwash efficacy on de-novo plaque formation

    National Research Council Canada - National Science Library

    Shivjot Chhina; Avnish Singh; Ipseeta Menon; Rickypal Singh; Anubhav Sharma; Vartika Aggarwal

    2016-01-01

    ...% chlorhexidine gluconate mouthwash on de novo plaque formation. Materials and Methods: This was a randomized, single blind, parallel, controlled clinical study with 90 healthy participants, with mean age of 27.19 +- 12.08 years...

  5. Inhibition of Bim enhances replication of varicella-zoster virus and delays plaque formation in virus-infected cells.

    Science.gov (United States)

    Liu, Xueqiao; Cohen, Jeffrey I

    2014-01-01

    Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication.

  6. Role of microglia in plaque formation in senile dementia of the Alzheimer type. An immunohistochemical study

    NARCIS (Netherlands)

    Rozemuller, J. M.; Eikelenboom, P.; Stam, F. C.

    1986-01-01

    Using immunohistochemical and enzyme histochemical methods, we have investigated the presence of mononuclear phagocytic cells around senile plaques in six brains from patients with senile dementia of the Alzheimer type (SDAT). It is generally supposed that reactive microglial cells are involved in

  7. Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions.

    Directory of Open Access Journals (Sweden)

    Onno J de Boer

    Full Text Available BACKGROUND: T cell mediated inflammation contributes to atherogenesis and the onset of acute cardiovascular disease. Effector T cell functions are under a tight control of a specialized T cell subset, regulatory T cells (Treg. At present, nothing is known about the in situ presence of Treg in human atherosclerotic tissue. In the present study we investigated the frequency of naturally occurring Treg cells in all developmental stages of human atherosclerotic lesions including complicated thrombosed plaques. METHODOLOGY: Normal arteries, early lesions (American Heart Association classification types I, II, and III, fibrosclerotic plaques (types Vb and Vc and 'high risk' plaques (types IV, Va and VI were obtained at surgery and autopsy. Serial sections were immunostained for markers specific for regulatory T cells (FOXP3 and GITR and the frequency of these cells was expressed as a percentage of the total numbers of CD3+ T cells. Results were compared with Treg counts in biopsies of normal and inflammatory skin lesions (psoriasis, spongiotic dermatitis and lichen planus. PRINCIPLE FINDINGS: In normal vessel fragments T cells were virtually absent. Treg were present in the intima during all stages of plaque development (0.5-5%. Also in the adventitia of atherosclerotic vessels Treg were encountered, in similar low amounts. High risk lesions contained significantly increased numbers of Treg compared to early lesions (mean: 3.9 and 1.2%, respectively. The frequency of FOXP3+ cells in high risk lesions was also higher compared to stable lesions (1.7%, but this difference was not significant. The mean numbers of intimal FOXP3 positive cells in atherosclerotic lesions (2.4% was much lower than those in normal (24.3% or inflammatory skin lesions (28%. CONCLUSION: Low frequencies of Treg in all developmental stages of human plaque formation could explain the smoldering chronic inflammatory process that takes place throughout the longstanding course of

  8. Animal models for plaque rupture: a biomechanical assessment

    NARCIS (Netherlands)

    van der Heiden, Kim; Hoogendoorn, Ayla; Daemen, Mat J.; Gijsen, Frank J. H.

    2016-01-01

    Rupture of atherosclerotic plaques is the main cause of acute cardiovascular events. Animal models of plaque rupture are rare but essential for testing new imaging modalities to enable diagnosis of the patient at risk. Moreover, they enable the design of new treatment strategies to prevent plaque

  9. Inhibition of Cariogenic Plaque Formation on Root Surface with Polydopamine-Induced-Polyethylene Glycol Coating

    OpenAIRE

    May Lei Mei; Quan-Li Li; Chun Hung Chu

    2016-01-01

    Root caries prevention has been a challenge for clinicians due to its special anatomical location, which favors the accumulation of dental plaque. Researchers are looking for anti-biofouling material to inhibit bacterial growth on exposed root surfaces. This study aimed to develop polydopamine-induced-polyethylene glycol (PEG) and to study its anti-biofouling effect against a multi-species cariogenic biofilm on the root dentine surface. Hydroxyapatite disks and human dentine blocks were divid...

  10. Erythrocyte membrane, plasma and atherosclerotic plaque lipid pattern in coronary heart disease Perfil lipídico de membrana de eritrocito, plasma y placa ateromatosa en la enfermedad coronaria

    Directory of Open Access Journals (Sweden)

    Natalia R. Lausada

    2007-10-01

    Full Text Available The objective was to analyze the lipid composition of the atherosclerotic plaque (AP, plasma and erythrocyte membrane (EM in patients with advanced coronary heart disease (CHD. AP were obtained through endarterectomy in 18 patients. Ten normolipemic healthy subjects were selected to obtain the normal lipid pattern profile. Total lipids of AP and EM were determined by HPTLC, and the fatty acid profile from AP, EM and plasma using TLC-FID. The relative amount of the lipid species analyzed in AP was in line with the data in the literature [phospholipids: 23.5 mol% ± 3.5; total cholesterol 68.9 mol% ± 7.9; triglyceride 7.6 mol% ± 3.4]. Plasma and EM from CHD patients compared to controls, showed a decrease in polyunsaturated fatty acids and an increase in saturated fatty acids leading to a decrease in the unsaturation index (plasma: 1.67 ± 0.06 vs. 1.28 ± 0.03, PEl objetivo fue analizar la composición lipídica de las membranas de eritrocitos (ME, plasma y placas ateromatosas (PA en pacientes con enfermedad coronaria avanzada (ECV. Las PA fueron obtenidas de endarterectomías coronarias de 18 pacientes. Fueron seleccionados 10 sujetos sanos, normolipémicos, como grupo control. Los lípidos totales de PA y ME se determinaron utilizando HPTLC, y el perfil de ácidos grasos de las PA, ME y plasma mediante TLC-FID. La cantidad relativa de las especies lipídicas obtenidas de las PA coinciden con la literatura [fosfolípidos 23.5 mol% ± 3.5; colesterol total 68.9 mol% ± 7.9; triglicéridos 7.6 mol% ± 3.4]. En el plasma y en las ME de los pacientes con ECV se observó, comparando con los pacientes controles, una disminución de los ácidos grasos poli-no saturados acompañado de un aumento de los ácidos grasos saturados que provocó el descenso del índice de instauración (plasma: 1.67 ± 0.06 vs. 1.28 ± 0.03, P<0.05; ME: 2.28 ± 0.04 vs. 1.25 ± 0.010, P<0.05 y el incremento del cociente AG saturados/insaturados (plasma: 0.35 ± 0.02 vs. 0

  11. The influence of chronic L-carnitine supplementation on the formation of preneoplastic and atherosclerotic lesions in the colon and aorta of male F344 rats.

    Science.gov (United States)

    Empl, Michael T; Kammeyer, Patricia; Ulrich, Reiner; Joseph, Jan F; Parr, Maria K; Willenberg, Ina; Schebb, Nils H; Baumgärtner, Wolfgang; Röhrdanz, Elke; Steffen, Christian; Steinberg, Pablo

    2015-11-01

    L-Carnitine, a key component of fatty acid oxidation, is nowadays being extensively used as a nutritional supplement with allegedly "fat burning" and performance-enhancing properties, although to date there are no conclusive data supporting these claims. Furthermore, there is an inverse relationship between exogenous supplementation and bioavailability, i.e., fairly high oral doses are not fully absorbed and thus a significant amount of carnitine remains in the gut. Human and rat enterobacteria can degrade unabsorbed L-carnitine to trimethylamine or trimethylamine-N-oxide, which, under certain conditions, may be transformed to the known carcinogen N-nitrosodimethylamine. Recent findings indicate that trimethylamine-N-oxide might also be involved in the development of atherosclerotic lesions. We therefore investigated whether a 1-year administration of different L-carnitine concentrations (0, 1, 2 and 5 g/l) via drinking water leads to an increased incidence of preneoplastic lesions (so-called aberrant crypt foci) in the colon of Fischer 344 rats as well as to the appearance of atherosclerotic lesions in the aorta of these animals. No significant difference between the test groups regarding the formation of lesions in the colon and aorta of the rats was observed, suggesting that, under the given experimental conditions, L-carnitine up to a concentration of 5 g/l in the drinking water does not have adverse effects on the gastrointestinal and vascular system of Fischer 344 rats.

  12. Vulnerable Plaque

    Science.gov (United States)

    ... Center > Vulnerable Plaque Menu Topics Topics FAQs Vulnerable Plaque Article Info En español Swelling (inflammation) is your ... aging, including coronary artery disease . What is vulnerable plaque? For many years, doctors have thought that the ...

  13. Maghemite nanoparticles and ferrous sulfate for the stimulation of iron plaque formation and arsenic immobilization in Phragmites australis.

    Science.gov (United States)

    Pardo, Tania; Martínez-Fernández, Domingo; de la Fuente, Carlos; Clemente, Rafael; Komárek, Michael; Bernal, M Pilar

    2016-12-01

    Wetland plants are considered as suitable biofilters for the removal of metal(loid)s and other contaminants from waters and wastewaters, due to their ability to accumulate and retain the contaminants in their roots. The iron plaque (IP) on the root surface influences the metal(loid)s retention processes. The stimulation of the IP development on roots of Phragmites australis by the external supply of a novel synthetic nanomaterial (nanomaghemite, nFe2O3) and FeSO4 (alone or in combination) was studied. An hydroponic experiment was carried out to evaluate the iron plaque formation after external iron addition, as well as their influence on arsenic immobilization capacity. Microscopic and spectroscopic techniques were utilized to assess the distribution of Fe and As in the roots. The addition of Fe stimulated the generation of the IP, especially when FeSO4 was involved. The nanoparticles alone were not efficient with regard to IP formation or As adsorption, even though they adhered to the root surface and did not enter into epithelial root cells. The combination of FeSO4 and nFe2O3 was the most effective treatment for improving the As removal capacity, and it seems to be an effective way to enhance the rhizofiltration potential of P. australis in As contaminated (waste)waters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. CAROTID ATHEROSCLEROTIC LESION IN YOUNG PATIENTS

    Directory of Open Access Journals (Sweden)

    N. V. Pizova

    2014-01-01

    Full Text Available Objective: to determine the incidence of atherosclerotic lesions in the carotid and vertebral arteries of young patients from Doppler ultrasound data and to compare the quantitatively assessed traditional risk factors of coronary heart disease (CHD with severe extracranial artery atherosclerotic lesion.Subjects and methods. Doppler ultrasound was carried out evaluating structural changes in the aortic arch branches in 1563 railway transport workers less than 45 years of age. A separate sample consisted of 68 young people with carotid atherosclerotic changes, in whom traditional risk factors for CHD were studied, so were in a control group of individuals without atherosclerotic changes (n = 38.Results. Among the examinees, carotid atherosclerotic lesion was detected in 112 (7.1 % cases, the increase in the rate of atherosclerotic plaques in patients aged 35–45 years being 9.08 %; that in the rate of local intima-media thickness in those aged 31–40 years being 5.1 %. Smoking (particularly that along with hypercholesterolemia and a family history of cardiovascular diseases, obesity (along with low activity, and emotional overstrain were defined as important risk factors in the young patients. Moreover, factor analysis has shown that smoking,hypertension, and early cardiovascular pathology in the next of kin makes the greatest contribution to the development of carotid atherosclerotic lesion.Conclusion. Among the patients less than 45 years of age, carotid and vertebral artery atherosclerotic changes were found in 112 (7.1 % cases, which were more pronounced in male patients. Smoking, particularly along with hypercholesterolemia and genetic predisposition to cardiovascular diseases, was a risk factor that had the highest impact on the degree of atherosclerotic lesion in the aortic arch branches of the young patients.

  15. In vivo and in vitro evidence that {sup 99m}Tc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery

    Energy Technology Data Exchange (ETDEWEB)

    Glaudemans, Andor W.J.M.; Vries, Erik F.J. de; Koole, Michel; Luurtsema, Gert; Slart, Riemer H.J.A. [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Bonanno, Elena [Univ. of Rome Tor Vergata (Italy). Dept. of Anatomic Pathology; Galli, Filippo [Sapienza Univ, Rome (Italy). Nuclear Medicine Unit; Zeebregts, Clark J. [University Medical Center Groningen (Netherlands). Surgery (Div. Vascular Surgery); Boersma, Hendrikus H. [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; University Medical Center Groningen (Netherlands). Clinical and Hospital Pharmacy; Taurino, Maurizio [Sapienza Univ., Rome (Italy). Vascular Surgery Unit; Signore, Alberto [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Sapienza Univ, Rome (Italy). Nuclear Medicine Unit

    2014-09-15

    Recent advances in basic science have established that inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Inflammatory cells are thought to be responsible for the transformation of a stable plaque into a vulnerable one. Lymphocytes constitute at least 20 % of infiltrating cells in these vulnerable plaques. Therefore, the interleukin-2 (IL-2) receptor, being overexpressed on activated T lymphocytes, may represent an attractive biomarker for plaque vulnerability. The aim of this study was to evaluate the specificity of radiolabelled IL-2 [{sup 99m}Tc-hydrazinonicotinamide (HYNIC)-IL-2] for imaging the lymphocytic infiltration in carotid plaques in vivo by planar and single photon emission computed tomography (SPECT)/CT imaging and ex vivo by microSPECT and autoradiography. For the in vivo study, ten symptomatic patients with advanced plaques at ultrasound who were scheduled for carotid endarterectomy underwent {sup 99m}Tc-HYNIC-IL-2 scintigraphy. The images were analysed visually on planar and SPECT images and semi-quantitatively on SPECT images by calculating target to background (T/B) ratios. After endarterectomy, immunomorphological evaluation and immunophenotyping were performed on plaque slices. For the ex vivo studies, four additional patients were included and, after in vitro incubation of removed plaques with {sup 99m}Tc-HYNIC-IL-2, autoradiography was performed and microSPECT images were acquired. Visual analysis defined clear {sup 99m}Tc-HYNIC-IL-2 uptake in seven of the ten symptomatic plaques. SPECT/CT allowed visualization in eight of ten. A significant correlation was found between the number of CD25+ lymphocytes and the total number of CD25+ cells in the plaque and the T/B ratio with adjacent carotid artery as background (Pearson's r = 0.89, p = 0.003 and r = 0.87, p = 0.005, respectively). MicroSPECT imaging showed clear {sup 99m}Tc-HYNIC-IL-2 uptake within the plaque wall and not in the lipidic core. With autoradiography

  16. A Preliminary Assessment of Silver Nanoparticle Inhibition of Monkeypox Virus Plaque Formation

    Directory of Open Access Journals (Sweden)

    Speshock Janice

    2008-01-01

    Full Text Available AbstractThe use of nanotechnology and nanomaterials in medical research is growing. Silver-containing nanoparticles have previously demonstrated antimicrobial efficacy against bacteria and viral particles. This preliminary study utilized an in vitro approach to evaluate the ability of silver-based nanoparticles to inhibit infectivity of the biological select agent, monkeypox virus (MPV. Nanoparticles (10–80 nm, with or without polysaccharide coating, or silver nitrate (AgNO3 at concentrations of 100, 50, 25, and 12.5 μg/mL were evaluated for efficacy using a plaque reduction assay. Both Ag-PS-25 (polysaccharide-coated, 25 nm and Ag-NP-55 (non-coated, 55 nm exhibited a significant (P ≤ 0.05 dose-dependent effect of test compound concentration on the mean number of plaque-forming units (PFU. All concentrations of silver nitrate (except 100 μg/mL and Ag-PS-10 promoted significant (P ≤ 0.05 decreases in the number of observed PFU compared to untreated controls. Some nanoparticle treatments led to increased MPV PFU ranging from 1.04- to 1.8-fold above controls. No cytotoxicity (Vero cell monolayer sloughing was caused by any test compound, except 100 μg/mL AgNO3. These results demonstrate that silver-based nanoparticles of approximately 10 nm inhibit MPV infection in vitro, supporting their potential use as an anti-viral therapeutic.

  17. Plaque of atherosclerosis in aorta: review on atherogenesis, formation of plaque, clinical significance, methods of imaging and treatment; Placa de aterosclerose em aorta: revisao sobre aterogenese, formacao de placa, significado clinco, metodos de imagens e tratamento

    Energy Technology Data Exchange (ETDEWEB)

    Furtado, Rogerio Gomes; Nunes, Colandy G. de Oliveira; Rassi Junior, Luis; Melato, Luciano Henrique; Turco, Fabio de Paula; Borges, Moises Marcos, E-mail: rogerinhofurtado@gmail.com [Centro de Diagnostico por Imagem (CDI), Goiania, GO (Brazil); Sara, Leonardo [Instituto do Coracao (InCor/FM/USP), Sao Paulo, SP (Brazil)

    2009-04-15

    There is a certain consensus in the literature that the earliest stage of atherogenesis is characterized by the accumulation of spongy cells in the region of the intimal artery. Risk factors such as arterial hypertension, smoking, diabetes mellitus, hypercholesterolemia, male gender and advanced age predispose a person to the formation of plaques in the coronaries and aorta. A greater number of acute coronary events as well as strokes have been observed in people with these risk factors. Strokes are the third cause of death in the USA, with about 40% of the cases being of cryptogenic origin. Since 1989 the atheroma plaques which develop in the thoracic aorta have been considered to be responsible for cerebral and peripheral strokes which were previously considered cryptogenic because imaging techniques such as electrocardiogram transesophageal, computerized tomogram, nuclear magnetic angio-resonance have visualized and characterized the lesions with plaques of arteriosclerosis in the thoracic aorta. The authors of this article made a systematic review in the PUBMED about arteriosclerosis in the aorta and its diagnostic methods. This review includes the physiopathology of the formation of atheroma to the aorta and its consequences, diagnostic methods such as echo transesophageal, computerized tomogram and angio resonance, as well as the advantages and disadvantages of each method of identification of the lesions. An analysis of the clinical significance of the size, form and location of the atheroma plaques in the thoracic aorta were made based on clinical studies, as well as their treatment with anticoagulants, antiplatelet and drugs to reduce cholesterol. (author)

  18. The effect of a new toothpaste containing potassium nitrate and triclosan on gingival health, plaque formation and dentine hypersensitivity.

    Science.gov (United States)

    Wara-aswapati, Nawarat; Krongnawakul, Duangporn; Jiraviboon, Duangporn; Adulyanon, Supreda; Karimbux, Nadeem; Pitiphat, Waranuch

    2005-01-01

    The purpose of this study was to investigate the effect of a new toothpaste containing an antiplaque and antiinflammatory agent (0.3% triclosan), a desensitizing agent (5% potassium nitrate) and an anticaries agent (0.76% sodium monofluorophosphate (SMFP)) on gingival health, plaque formation and dentine hypersensitivity in a 12-week home study. The efficacy of the test toothpaste was compared with that of a control toothpaste containing 5% potassium nitrate and 0.76% SMFP and a benchmark product containing only 0.76% SMFP. One hundred and two healthy volunteers, who had a minimum of 20 natural permanent teeth with no probing depth >4 mm and at least one sensitive tooth, participated in this study. Following enrollment, the subjects received a dental prophylaxis and instruction in brushing technique. After a 4-week pre-experimental phase, baseline gingival bleeding index (GBI), plaque index (PI) and visual analogue scales (VASs) indicating dentine hypersensitivity levels responding to tactile and air stimuli were assessed. The subjects were then randomly given one of the three toothpastes; test, control, or benchmark toothpaste, and a soft-filamented toothbrush for home use. The GBI, PI and VASs were re-examined at weeks 4 and 12. Overall, the GBI scores were significantly reduced compared with baseline in all groups (ptoothpaste was effective in reducing dentine hypersensitivity. More studies are needed to further determine the potential interaction between triclosan and potassium nitrate in dentifrices. Copyright Blackwell Munksgaard, 2004.

  19. Early enriched environment exposure protects spatial memory and accelerates amyloid plaque formation in APP(Swe/PS1(L166P mice.

    Directory of Open Access Journals (Sweden)

    Francesca Montarolo

    Full Text Available Enriched environment exposure improves several aspects of cognitive performance in Alzheimer's disease patients and in animal models and, although the role of amyloid plaques is questionable, several studies also assessed their response to enriched environment, with contrasting results. Here we report that rearing APP(Swe/PS1(L166P mice in an enriched environment since birth rescued the spatial memory impairment otherwise present at 6 months of age. At the same time, the exposure to the enriched environment caused a transient acceleration of plaque formation, while there was no effect on intracellular staining with the 6E10 antibody, which recognizes β-amyloid, full length amyloid precursor protein and its C-terminal fragments. The anticipation of plaque formation required exposure during early development, suggesting an action within critical periods for circuits formation. On the other hand, chronic neuronal activity suppression by tetrodotoxin decreased the number of plaques without affecting intracellular amyloid. These results indicate that enriched environment exposure since early life has a protective effect on cognitive deterioration although transiently accelerates amyloid deposition. In addition, the effects of the enriched environment might be due to increased neuronal activity, because plaques were reduced by suppression of electrical signaling by tetrodotoxin.

  20. The effects of enhanced zinc on spatial memory and plaque formation in transgenic mice

    Science.gov (United States)

    Linkous, D.H.; Adlard, P.A.; Wanschura, P.B.; Conko, K.M.; Flinn, J.M.

    2009-01-01

    There is considerable evidence suggesting that metals play a central role in the pathogenesis of Alzheimer's disease. Reports suggest that elevated dietary metals may both precipitate and potentiate an Alzheimer's disease phenotype. Despite this, there remain few studies that have examined the behavioral consequences of elevated dietary metals in wild type and Alzheimer's disease animals. To further investigate this in the current study, two separate transgenic models of AD (Tg2576 and TgCRND8), together with wild type littermates were administered 10 ppm (0.153 mM) Zn. Tg2576 animals were maintained on a zinc-enriched diet both pre- and postnatally until 11 months of age, while TgCRND8 animals were treated for five months following weaning. Behavioral testing, consisting of "Atlantis" and "moving" platform versions of the Morris water maze, were conducted at the end of the study, and tissues were collected for immunohistochemical analysis of amyloid-β burden. Our data demonstrate that the provision of a zinc-enriched diet potentiated Alzheimer-like spatial memory impairments in the transgenic animals and was associated with reduced hippocampal amyloid-β plaque deposits. Zinc-related behavioral deficits were also demonstrated in wild type mice, which were sometimes as great as those present in the transgenic animals. However, zinc-related cognitive impairments in transgenic mice were greater than the summation of zinc effects in the wild type mice and the transgene effects.

  1. Intracellular amyloid-β accumulation in calcium-binding protein-deficient neurons leads to amyloid-β plaque formation in animal model of Alzheimer's disease.

    Science.gov (United States)

    Moon, Minho; Hong, Hyun-Seok; Nam, Dong Woo; Baik, Sung Hoon; Song, Hyundong; Kook, Sun-Young; Kim, Yong Soo; Lee, Jeewoo; Mook-Jung, Inhee

    2012-01-01

    One of the major hallmarks of Alzheimer's disease (AD) is the extracellular deposition of amyloid-β (Aβ) as senile plaques in specific brain regions. Clearly, an understanding of the cellular processes underlying Aβ deposition is a crucial issue in the field of AD research. Recent studies have found that accumulation of intraneuronal Aβ (iAβ) is associated with synaptic deficits, neuronal death, and cognitive dysfunction in AD patients. In this study, we found that Aβ deposits had several shapes and sizes, and that iAβ occurred before the formation of extracellular amyloid plaques in the subiculum of 5XFAD mice, an animal model of AD. We also observed pyroglutamate-modified Aβ (N3pE-Aβ), which has been suggested to be a seeding molecule for senile plaques, inside the Aβ plaques only after iAβ accumulation, which argues against its seeding role. In addition, we found that iAβ accumulates in calcium-binding protein (CBP)-free neurons, induces neuronal death, and then develops into senile plaques in 2-4-month-old 5XFAD mice. These findings suggest that N3pE-Aβ-independent accumulation of Aβ in CBP-free neurons might be an early process that triggers neuronal damage and senile plaque formation in AD patients. Our results provide new insights into several long-standing gaps in AD research, namely how Aβ plaques are formed, what happens to iAβ and how Aβ causes selective neuronal loss in AD patients.

  2. A randomized clinical study for comparative evaluation of Aloe Vera and 0.2% chlorhexidine gluconate mouthwash efficacy on de-novo plaque formation.

    Science.gov (United States)

    Chhina, Shivjot; Singh, Avnish; Menon, Ipseeta; Singh, Rickypal; Sharma, Anubhav; Aggarwal, Vartika

    2016-01-01

    To comparatively assess the antiplaque efficacy of Aloe vera mouthwash and 0.2% chlorhexidine gluconate mouthwash on de novo plaque formation. This was a randomized, single blind, parallel, controlled clinical study with 90 healthy participants, with mean age of 27.19 ± 12.08 years. After thorough oral prophylaxis, participants were instructed to discontinue mechanical plaque control. Participants were divided randomly into three groups; pure Aloe vera mouthwash was dispensed to the test group; control group received 0.2% chlorhexidine gluconate mouthwash; in Placebo group, flavored distilled water was used as oral rinse twice daily. Effect on 4-day de novo plaque formation was assessed by comparing pre-rinsing Quigley Hein Modified Plaque Scores were analyzed statistically using analysis of variance and Student's t-test. Post-rinsing control group showed the least plaque score which was comparable to the test group. Both the control group and test group showed significant difference with the placebo group. Herbal mouthwash containing Aloe vera mouthwash has comparable antiplaque efficacy as the gold standard 0.2% chlorhexidine gluconate with fewer side effects and can be considered as an alternative.

  3. No evidence for involvement of plasma proteins or blood-borne cells in amyloid plaque formation in scrapie-affected mice. An immunohistoperoxidase study

    NARCIS (Netherlands)

    Eikelenboom, P.; Scott, J. R.; McBride, P. A.; Rozemuller, J. M.; Bruce, M. E.; Fraser, H.

    1987-01-01

    The present study was designed to investigate blood-brain permeability and the possible involvement of plasma proteins and blood-borne cells in amyloid plaque formation in scrapie-affected mice. No abnormal extravasation of intravenously injected horseradish peroxidase (HRP) was found and with

  4. Activation of calpain-1 in human carotid artery atherosclerotic lesions

    Directory of Open Access Journals (Sweden)

    Pedro Luis M

    2009-06-01

    Full Text Available Abstract Background In a previous study, we observed that oxidized low-density lipoprotein-induced death of endothelial cells was calpain-1-dependent. The purpose of the present paper was to study the possible activation of calpain in human carotid plaques, and to compare calpain activity in the plaques from symptomatic patients with those obtained from patients without symptoms. Methods Human atherosclerotic carotid plaques (n = 29, 12 associated with symptoms were removed by endarterectomy. Calpain activity and apoptosis were detected by performing immunohistochemical analysis and TUNEL assay on human carotid plaque sections. An antibody specific for calpain-proteolyzed α-fodrin was used on western blots. Results We found that calpain was activated in all the plaques and calpain activity colocalized with apoptotic cell death. Our observation of autoproteolytic cleavage of the 80 kDa subunit of calpain-1 provided further evidence for enzyme activity in the plaque samples. When calpain activity was quantified, we found that plaques from symptomatic patients displayed significantly lower calpain activity compared with asymptomatic plaques. Conclusion These novel results suggest that calpain-1 is commonly active in carotid artery atherosclerotic plaques, and that calpain activity is colocalized with cell death and inversely associated with symptoms.

  5. Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration

    NARCIS (Netherlands)

    van der Valk, Fleur M.; van Wijk, Diederik F.; Lobatto, Mark E.; Verberne, Hein J.; Storm, G|info:eu-repo/dai/nl/073356328; Willems, Martine C M; Legemate, Dink A.; Nederveen, Aart J.; Calcagno, Claudia; Mani, Venkatesh; Ramachandran, Sarayu; Paridaans, Maarten P M; Otten, Maarten J.; Dallinga-Thie, Geesje M.; Fayad, Zahi A.; Nieuwdorp, Max; Schulte, Dominik M.; Metselaar, Josbert M.|info:eu-repo/dai/nl/244207690; Mulder, Willem J M; Stroes, Erik S.

    2015-01-01

    Drug delivery to atherosclerotic plaques via liposomal nanoparticles may improve therapeutic agents' risk-benefit ratios. Our paper details the first clinical studies of a liposomal nanoparticle encapsulating prednisolone (LN-PLP) in atherosclerosis. First, PLP's liposomal encapsulation improved its

  6. Long-term stable expression of human apolipoprotein A-I mediated by helper-dependent adenovirus gene transfer inhibits atherosclerosis progression and remodels atherosclerotic plaques in a mouse model of familial hypercholesterolemia.

    Science.gov (United States)

    Belalcazar, L Maria; Merched, Aksam; Carr, Boyd; Oka, Kazuhiro; Chen, Kuang-Hua; Pastore, Lucio; Beaudet, Arthur; Chan, Lawrence

    2003-06-03

    Epidemiologic studies and transgenic mouse experiments indicate that high plasma HDL and apolipoprotein (apo) A-I protect against atherosclerosis. We used helper-dependent adenovirus (HD-Ad) gene transfer to examine the effect of long-term hepatic apoA-I expression on atherosclerotic lesion progression and remodeling in a mouse model of familial hypercholesterolemia. We treated LDL receptor-deficient (LDLR-/-) mice maintained on a high-cholesterol diet for 6 weeks with either a HD-Ad containing human apoA-I gene (HD-Ad-AI) or saline (control). HD-Ad-AI treatment did not affect plasma liver enzymes but induced the appearance of plasma human apoA-I at or above human levels for the duration of the study. Substantial amounts of human apoA-I existed in lipid-free plasma. Compared with controls, HDLs from treated mice were larger and had a greater inhibitory effect on tumor necrosis factor-alpha-induced vascular cellular adhesion molecule-1 expression in cultured endothelial cells. Twenty-four weeks after injection, aortic atherosclerotic lesion area in saline-treated mice progressed approximately 700%; the rate of progression was reduced by >50% by HD-Ad-AI treatment. The lesions in HD-Ad-AI-treated mice contained human apoA-I that colocalized mainly with macrophages; they also contained less lipid, fewer macrophages, and less vascular cellular adhesion molecule-1 immunostaining but more smooth muscle cells (alpha-actin staining) and collagen. HD-Ad-AI treatment of LDLR-/- mice leads to long-term overexpression of apoA-I, retards atherosclerosis progression, and remodels the lesions to a more stable-appearing phenotype. HD-Ad-mediated transfer of apoA-I may be a useful clinical approach for protecting against atherosclerosis progression and stabilizing atherosclerotic lesions associated with dyslipidemia in human patients.

  7. Human Alternative Macrophages Populate Calcified Areas of Atherosclerotic Lesions and Display Impaired RANKL-Induced Osteoclastic Bone Resorption Activity.

    Science.gov (United States)

    Chinetti-Gbaguidi, Giulia; Daoudi, Mehdi; Rosa, Mickael; Vinod, Manjula; Louvet, Loïc; Copin, Corinne; Fanchon, Mélanie; Vanhoutte, Jonathan; Derudas, Bruno; Belloy, Loic; Haulon, Stephan; Zawadzki, Christophe; Susen, Sophie; Massy, Ziad A; Eeckhoute, Jérôme; Staels, Bart

    2017-06-23

    Vascular calcification is a process similar to bone formation leading to an inappropriate deposition of calcium phosphate minerals in advanced atherosclerotic plaques. Monocyte-derived macrophages, located in atherosclerotic lesions and presenting heterogeneous phenotypes, from classical proinflammatory M1 to alternative anti-inflammatory M2 macrophages, could potentially display osteoclast-like functions. To characterize the phenotype of macrophages located in areas surrounding the calcium deposits in human atherosclerotic plaques. Macrophages near calcium deposits display an alternative phenotype being both CD68 and mannose receptor-positive, expressing carbonic anhydrase type II, but relatively low levels of cathepsin K. In vitro interleukin-4-polarization of human primary monocytes into macrophages results in lower expression and activity of cathepsin K compared with resting unpolarized macrophages. Moreover, interleukin-4 polarization lowers expression levels of the osteoclast transcriptional activator nuclear factor of activated T cells type c-1, associated with increased gene promoter levels of the transcriptional repression mark H3K27me3 (histone 3 lysine 27 trimethylation). Despite higher expression of the receptor activator of nuclear factor κB receptor, receptor activator of nuclear factor κB ligand/macrophage colony-stimulating factor induction of nuclear factor of activated T cells type c-1 and cathepsin K expression is defective in these macrophages because of reduced Erk/c-fos-mediated downstream signaling resulting in impaired bone resorption capacity. These results indicate that macrophages surrounding calcium deposits in human atherosclerotic plaques are phenotypically defective being unable to resorb calcification. © 2017 American Heart Association, Inc.

  8. Salusins: Potential Use as a Biomarker for Atherosclerotic Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    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.

  9. Vulnerable plaque detection: The role of 18-fluorine ...

    African Journals Online (AJOL)

    Positron emission tomography computed tomography (PET-CT) is a combined functional and structural multi modality imaging tool that can be utilized to detect vulnerable and atherosclerotic plaques. In this study we observe the prevalence of active and calcified plaques in selected arteries during whole-body 18F-FDG ...

  10. Localization of oxidized low-density lipoprotein and its relation to plaque morphology in human coronary artery.

    Directory of Open Access Journals (Sweden)

    Yasumi Uchida

    Full Text Available OBJECTIVES: Oxidized low-density lipoprotein (oxLDL plays a key role in the formation of atherosclerotic plaques. However, its localization in human coronary arterial wall is not well understood. The present study was performed to visualize deposition sites and patterns of native oxLDL and their relation to plaque morphology in human coronary artery. METHODS: Evans blue dye (EB elicits a violet fluorescence by excitation at 345-nm and emission at 420-nm, and a reddish-brown fluorescence by excitation at 470-nm and emission at 515-nm characteristic of oxLDL only. Therefore, native oxLDL in excised human coronary artery were investigated by color fluorescent microscopy (CFM using EB as a biomarker. RESULTS: (1 By luminal surface scan with CFM, the % incidence of oxLDL in 38 normal segments, 41 white plaques and 32 yellow plaques that were classified by conventional angioscopy, was respectively 26, 44 and 94, indicating significantly (p<0.05 higher incidence in the latter than the former two groups. Distribution pattern was classified as patchy, diffuse and web-like. Web-like pattern was observed only in yellow plaques with necrotic core. (2 By transected surface scan, oxLDL deposited within superficial layer in normal segments and diffusely within both superficial and deep layers in white and yellow plaques. In yellow plaques with necrotic core, oxLDL deposited not only in the marginal zone of the necrotic core but also in the fibrous cap. CONCLUSION: Taken into consideration of the well-known process of coronary plaque growth, the results suggest that oxLDL begins to deposit in human coronary artery wall before plaque formation and increasingly deposits with plaque growth, exhibiting different deposition sites and patterns depending on morphological changes.

  11. Determining carotid plaque vulnerability using ultrasound center frequency shifts.

    Science.gov (United States)

    Erlöv, Tobias; Cinthio, Magnus; Edsfeldt, Andreas; Segstedt, Simon; Dias, Nuno; Nilsson, Jan; Gonçalves, Isabel

    2016-03-01

    The leading cause of morbidity and mortality worldwide is atherosclerotic cardiovascular disease, most commonly caused by rupture of a high-risk plaque and subsequent thrombosis resulting in stroke, myocardial infarction or sudden death depending on the affected arterial territory. Accurate, non-invasive methods to identify such lesions known as vulnerable or high-risk plaques are currently sub-optimal. Our aim was to validate a new non-invasive ultrasound method to identify high-risk carotid plaques. We evaluated a new method based on the center frequency shift (CFS) of the ultrasound radio frequency data obtained from carotid plaques compared to a reference phantom. We evaluated the method both ex vivo, on 157 sections from 18 plaques, and in vivo, in 39 patients 1-day prior to carotid plaque removal, and correlated the data with histology. The CFS correlated with a plaque vulnerability index based on histological areas stained for lipids, macrophages, hemorrhage, smooth muscle cells and collagen (r = -0.726, P = 1.7 × 10(-8)). Plaques with CFS below median had larger cores, more macrophages and were less rich in collagen in agreement with the definition of rupture-prone plaques. The accuracy to detect plaques with high vulnerability index was 78% (confidence interval (CI) 61-89%), with sensitivity 77% (CI 61-89%) and specificity 78% (CI 62-89%). Our method is the first to characterize atherosclerotic plaque components that affect plaque vulnerability using CFS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Intravascular Ultrasound Elastography: A Clinician's Tool for Assessing Vulnerability and Material Composition of Plaques.

    NARCIS (Netherlands)

    Baldewsing, R.A.; Schaar, J.A.; Korte, C.L. de; Mastik, F.; Serruys, P.W.; Steen, A.F.W. van der

    2005-01-01

    The material composition and morphology of the atherosclerotic plaque components are considered to be more important determinants of acute coronary ischemic syndromes than the degree of stenosis. When a vulnerable plaque ruptures it causes an acute thrombotic reaction. Rupture prone plaques contain

  13. MRI-based biomechanical parameters for carotid artery plaque vulnerability assessment

    NARCIS (Netherlands)

    Speelman, Lambert; Teng, Zhongzhao; Nederveen, Aart J.; van der Lugt, Aad; Gillard, Jonathan H.

    2016-01-01

    Carotid atherosclerotic plaques are a major cause of ischaemic stroke. The biomechanical environment to which the arterial wall and plaque is subjected to plays an important role in the initiation, progression and rupture of carotid plaques. MRI is frequently used to characterize the morphology of a

  14. Spiral computed tomographic imaging related to computerized ultrasonographic images of carotid plaque morphology and histology

    DEFF Research Database (Denmark)

    Grønholdt, Marie-Louise; Wagner, A; Wiebe, B M

    2001-01-01

    Echolucency of carotid atherosclerotic plaques, as evaluated by computerized B-mode ultrasonographic images, has been associated with an increased incidence of brain infarcts on cerebral computed tomographic scans. We tested the hypotheses that characterization of carotid plaques on spiral computed...... tomographic images correlates with that on computerized B-mode ultrasonographic images and that spiral computed tomographic imaging predicts the histomorphometric plaque content....

  15. The association between gallstone disease and plaque in the abdominopelvic arteries

    Directory of Open Access Journals (Sweden)

    Halil Ibrahim Serin

    2017-01-01

    Full Text Available Background: The aim of this study was to assess the atheromatous plaque, in the abdominopelvic arteries as a marker of cardiac risk in patients with or without gallstone disease (GD. Materials and Methods: A total of 136 patients were enrolled in this cross-sectional study. Forty-eight patients had GD and the remaining 88 patients did not. The presence or absence of gallstones was noted during abdominal ultrasonography while vascular risk factors such as plaque formation, intima-media thickness, plaque calcification, mural thrombus, stenosis, aneurysm, and inflammation were recorded during an abdominopelvic computed tomography scan. In addition, percentage of the abdominopelvic aorta surface covered by atheromatous plaque was calculated. Results: The mean age of patients with GD and without GD was 50.81 ± 16.20 and 50.40 ± 12.43, respectively. Patients with GD were more likely to have diabetes mellitus, a higher body mass index (BMI (P < 0.001, and higher cholesterol (P < 0.01, and low-density lipoprotein-cholesterol (P < 0.02 levels. No significant differences were found between the groups regarding other atherosclerotic risk factors. Patients with GD had significantly higher rates of the vascular risk factors as intima-media thickness, plaque formation, calcification, aneurysm, mural thrombosis, stenosis, and inflammation in all abdominal arterial segments other than aneurysm in the femoral arteries. In addition, patients with GD had severe atheromatous plaques in the abdominal aorta, common iliac, external iliac, and common femoral artery (CFA. In patients with GD, parameters of age, BMI, and systolic and diastolic blood pressure were all correlated with the severity of the atheromatous plaque in abdominal aorta, common iliac, external iliac, and CFA. Conclusion: We demonstrated a direct relationship between GD and abdominopelvic atheromatous plaque, which is a marker for increased cardiovascular risk, for the first time in the literature

  16. Roles of root porosity, radial oxygen loss, Fe plaque formation on nutrient removal and tolerance of wetland plants to domestic wastewater.

    Science.gov (United States)

    Mei, Xiu-Qin; Yang, Yang; Tam, Nora Fung-Yee; Wang, Ya-Wen; Li, Li

    2014-03-01

    Root properties including rates of radial oxygen loss (ROL), root porosity, and Fe plaque formation on the root surface, in six wetland plant species, namely Acorus calamus, Arundo donax var. versicolor, Cyperus flabelliformis, Canna indica, Iris tectorum, and Scirpus validus, and their relationships with nutrient removal and tolerance to domestic wastewater were investigated. Results showed that different species had different root porosities (18-36%) and Fe plaque formation (1.76-5.3 mg Fe g(-1) root d.w.), which were significantly correlated with ROL (67-157 mmol O2 kg(-1) root d.w. d(-1)) (p plant tolerance to domestic wastewater (p oxygen demand (58-86%). Among the six species, C. flabelliformis and C. indica had significantly higher ROL, greater Fe plaque formation, higher tolerance to domestic wastewater, and better removal of TN, TP, and COD. These two species also had greater influences on changes in redox potential, pH, dissolved oxygen, and the quotients of [NH4(+)-N]:[NO3(-)-N] in rhizosphere soil solution, as well as greater N and P uptake in plant tissues, particularly belowground parts, than in the other species. For all plant species investigated, wastewater significantly decreased the rates of ROL and root porosity but induced greater Fe plaque formation. These results suggested that root properties are useful for selecting tolerant and efficient species in constructed wetland wastewater treatment facilities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits.

    Directory of Open Access Journals (Sweden)

    Smita Majumder

    Full Text Available Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-β (Aβ. However, the effects of inducing autophagy on plaques and tangles are yet to be determined. While soluble Aβ and tau represent toxic species in Alzheimer's disease (AD pathogenesis, there is well documented evidence that plaques and tangles also are detrimental to normal brain function. Thus, it is critical to assess the effects of inducing autophagy in an animal model with established plaques and tangles. Here we show that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits. In contrast, inducing autophagy in 15-month-old 3xTg-AD mice, which have established plaques and tangles, has no effects on AD-like pathology and cognitive deficits. In conclusion, we show that autophagy induction via rapamycin may represent a valid therapeutic strategy in AD when administered early in the disease progression.

  18. Targeting of matrix metalloproteinase activation for noninvasive detection of vulnerable atherosclerotic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hartung, Dagmar [University of California, School of Medicine, Irvine, CA (United States); School of Medicine, Department of Radiology, Hannover (Germany); Schaefers, Michael; Kopka, Klaus [University of Muenster, Department of Nuclear Medicine, Muenster (Germany); Fujimoto, Shinichiro; Narula, Navneet; Petrov, Artiom; Narula, Jagat [University of California, School of Medicine, Irvine, CA (United States); Levkau, Bodo [University of Duisburg-Essen, Institute of Pathophysiology, Duisburg (Germany); Virmani, Renu; Kolodgie, Frank D. [Cardiovascular Pathology, Gaithersburg, MD (United States); Reutelingsperger, Chris; Hofstra, Leo [Cardiovascular Research Institute, Maastricht (Netherlands)

    2007-06-15

    Inflammation plays an important role in vulnerability of atherosclerotic plaques to rupture and hence acute coronary events. The monocyte-macrophage infiltration in plaques leads to upregulation of cytokines and metalloproteinase enzymes. Matrix metalloproteinases result in matrix dissolution and consequently expansive remodeling of the vessel. They also contribute to attenuation of fibrous cap and hence susceptibility to rupture. Assessment of metalloproteinase expression and activity should provide information about plaque instability. (orig.)

  19. Quantitative coronary plaque analysis predicts high-risk plaque morphology on coronary computed tomography angiography: results from the ROMICAT II trial.

    Science.gov (United States)

    Liu, Ting; Maurovich-Horvat, Pál; Mayrhofer, Thomas; Puchner, Stefan B; Lu, Michael T; Ghemigian, Khristine; Kitslaar, Pieter H; Broersen, Alexander; Pursnani, Amit; Hoffmann, Udo; Ferencik, Maros

    2018-02-01

    Semi-automated software can provide quantitative assessment of atherosclerotic plaques on coronary CT angiography (CTA). The relationship between established qualitative high-risk plaque features and quantitative plaque measurements has not been studied. We analyzed the association between quantitative plaque measurements and qualitative high-risk plaque features on coronary CTA. We included 260 patients with plaque who underwent coronary CTA in the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) II trial. Quantitative plaque assessment and qualitative plaque characterization were performed on a per coronary segment basis. Quantitative coronary plaque measurements included plaque volume, plaque burden, remodeling index, and diameter stenosis. In qualitative analysis, high-risk plaque was present if positive remodeling, low CT attenuation plaque, napkin-ring sign or spotty calcium were detected. Univariable and multivariable logistic regression analyses were performed to assess the association between quantitative and qualitative high-risk plaque assessment. Among 888 segments with coronary plaque, high-risk plaque was present in 391 (44.0%) segments by qualitative analysis. In quantitative analysis, segments with high-risk plaque had higher total plaque volume, low CT attenuation plaque volume, plaque burden and remodeling index. Quantitatively assessed low CT attenuation plaque volume (odds ratio 1.12 per 1 mm 3 , 95% CI 1.04-1.21), positive remodeling (odds ratio 1.25 per 0.1, 95% CI 1.10-1.41) and plaque burden (odds ratio 1.53 per 0.1, 95% CI 1.08-2.16) were associated with high-risk plaque. Quantitative coronary plaque characteristics (low CT attenuation plaque volume, positive remodeling and plaque burden) measured by semi-automated software correlated with qualitative assessment of high-risk plaque features.

  20. Carotid plaque, intima-media thickness, and incident aortic stenosis

    DEFF Research Database (Denmark)

    Martinsson, Andreas; Östling, Gerd; Persson, Margaretha

    2014-01-01

    OBJECTIVE: Aortic stenosis (AS) shares risk factors with atherosclerotic vascular disease. Carotid intima-media thickness (IMT) and plaque may reflect the cumulative damage from exposure to different atherosclerotic risk factors. We examined the relationship of carotid IMT and plaque with incident...... AS in a prospective population-based study. APPROACH AND RESULTS: A random sample of participants (age, 45-68 years) in the population-based Malmö Diet and Cancer Study underwent B-mode ultrasound with measurements of IMT and the presence of plaque in the common carotid artery (n=5079). Potential risk factors......-density lipoprotein cholesterol, hypertension, diabetes mellitus, smoking, C-reactive protein, plaque, and IMT. In contrast, high-density lipoprotein cholesterol, triglycerides, height, and leukocyte count were not significantly associated with AS (P>0.05). After adjustments, IMT, plaque, age, smoking, C...

  1. Plaque characterization in ex vivo MRI evaluated by dense 3D correspondence with histology

    DEFF Research Database (Denmark)

    van Engelen, Arna; de Bruijne, Marleen; Klein, Stefan

    2011-01-01

    Automatic quantification of carotid artery plaque composition is important in the development of methods that distinguish vulnerable from stable plaques. MRI has shown to be capable of imaging different components noninvasively. We present a new plaque classification method which uses 3D....... Histological slices of human atherosclerotic plaques were manually segmented into necrotic core, fibrous tissue and calcification. Classification of these three components was voxelwise evaluated. As features the intensity, gradient magnitude and Laplacian in four MRI sequences after different degrees...

  2. 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.)

  3. A role for archaeal organisms in development of atherosclerotic vulnerable plaques and myxoid matrices Um papel para organismos de arqueia no desenvolvimento de placas ateroscleróticas vulner��veis e matriz mixomatosa

    Directory of Open Access Journals (Sweden)

    Maria L Higuchi

    2006-10-01

    Full Text Available PURPOSE: Vulnerable plaques are characterized by a myxoid matrix, necrotic lipidic core, reactive oxygen species, and high levels of microorganisms. Aerobic microbes such as Chlamydophila pneumoniae and Mycoplasma pneumoniae usually do not survive in oxidative stress media. Archaea are anaerobic microbes with powerful anti-oxidative enzymes that allow detoxification of free radicals whose presence might favor the survival of aerobic microorganisms. We searched for archaeal organisms in vulnerable plaques, and possible associations with myxoid matrix, chlamydia, and mycoplasma bodies. METHODS: Twenty-nine tissue samples from 13 coronary artherectomies from large excentric ostial or bifurcational lesions were studied using optical and electron microscopy. Infectious agents compatible with archaea, chlamydia, and mycoplasma were semiquantified using electron micrographs and correlated with the amounts of fibromuscular tissue, myxoid matrix, and foam cells, as determined from semi-thin sections. Six of the cases were also submitted to polymerase chain reaction with archaeal primers. RESULTS: All 13 specimens showed archaeal-compatible structures and chlamydial and mycoplasmal bodies in at least 1 sample. There was a positive correlation between extent of the of myxoid matrix and archaeal bodies (r = 0.44, P = 0.02; between archaeal and mycoplasmal bodies (r = 0.41, P = 0.03, and between chlamydial bodies and foam cells (r = 0.42; P = 0.03. The PCR test was positive for archaeal DNA in 4 of the 6 fragments. DISCUSSION: DNA and forms suggestive of archaea are present in vulnerable plaques and may have a fundamental role in the proliferation of mycoplasma and chlamydia. This seems to be the first description of apparently pathogenic archaea in human internal organ lesions.PROPOSTA: Placas vulneráveis são caracterizadas por matriz mixomatosa, centro lipídico necrótico, espécies reativas de oxigênio e alto níveis de microorganismos. Micróbios aer

  4. Mechanical stresses in carotid plaques using MRI-based fluid-structure interaction models

    DEFF Research Database (Denmark)

    Kock, Samuel A; Nygaard, Jens Vinge; Eldrup, Nikolaj

    2008-01-01

    fluid-structure interaction (FSI) simulations of carotid atherosclerotic plaques were performed facilitating in-vivo estimation of longitudinal internal fibrous cap stresses. The FSI simulation combined finite element analysis (FEA) with computational fluid dynamics (CFD) simulations of blood...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Zhang, Meng; Zhao, Hongting; Cai, Jing; Li, Huihui; Wu, Qi; Qiao, Tong; Li, Kuanyu

    2017-01-01

    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 atherosclerotic

  7. Temporal and Quantitative Analysis of Atherosclerotic Lesions in Diet-Induced Hypercholesterolemic Rabbits

    Directory of Open Access Journals (Sweden)

    Qi Yu

    2012-01-01

    Full Text Available The diet-induced atherosclerotic rabbit is an ideal model for atherosclerosis study, but temporal changes in atherosclerotic development in hypercholesterolemic rabbits are poorly understood. Japanese white rabbits were fed a high-cholesterol diet to induce sustained hypercholesterolemia, and each group of 10–12 animals was then sacrificed at 6, 12, 16, or 28 weeks. The rabbit aortas were harvested, and the sizes of the gross and intima atherosclerotic lesions were quantified. The cellular component of macrophages (Mφs and smooth muscle cells (SMCs in aortic intimal lesions was also quantified by immunohistochemical staining, and the correlation between plasma cholesterol levels and the progress of atherosclerotic lesions was studied. The ultrastructure of the atherosclerotic lesions was observed by transmission electron microscopy (TEM. Widely variable atherosclerotic plaques were found from 6 weeks to 28 weeks, and the lesional progress was closely correlated with cholesterol exposure. Interestingly, a relatively reduced accumulation of Mφ, an increased numbers of SMCs, and a damaged endothelial layer were presented in advanced lesions. Moreover, SMCs were closely correlated with cholesterol exposure and lesional progress for the whole period. Cholesterol exposure directly determines atherosclerotic progress in a rabbit model, and the changes in the cellular component of advanced lesions may affect plaque stability in an atherosclerotic rabbit model.

  8. 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III cholesterol guidelines applied to HIV-infected patients with/without subclinical high-risk coronary plaque

    National Research Council Canada - National Science Library

    Zanni, Markella V; Fitch, Kathleen V; Feldpausch, Meghan; Han, Allison; Lee, Hang; Lu, Michael T; Abbara, Suhny; Ribaudo, Heather; Douglas, Pamela S; Hoffmann, Udo; Lo, Janet; Grinspoon, Steven K

    2014-01-01

    ...) coronary atherosclerotic plaque. To compare recommendations for statins among HIV-infected subjects with/without HRM coronary plaque according to 2013 ACC/AHA versus 2004 Adult Treatment Panel III guidelines...

  9. The effect of two different oral antiseptics on dental plaque formation (De Novo Biofilm and on gingival inflammation

    Directory of Open Access Journals (Sweden)

    Zelić Obrad

    2009-01-01

    Full Text Available Introduction. Since the discovery that periodontal diseases are caused by microbial plaque the interest of many scientists has been focused on oral antiseptics. There are very few mouthrinses with oral antiseptic effect originally designed in our country. One of these is Ozosept® solution. Objective. This study evaluated the effect of Ozosept® solution (phenol compound on the oral hygiene and gingival inflammation, in comparison with Hibidex DAP® solution (chlorhexidine digluconate. Methods. Two groups, each of 21 persons, which did not significantly differ concerning Silness-Löe plaque index (PI and Löe-Sillnes gingival index (GI, used one of the studied oral antiseptic for a 15-day period. Oral hygiene was maintained by subjects' habitual home methods, and no technique of professionally advised brushing was performed during the experimental period. Results. At the end of the study, PI and GI scores were lowered to a statistically high significance in both groups of participants in comparison to the indexes at the beginning of the study. At the end of the study, PI and GI scores did not significantly differ between the two analyzed groups. No side effects, which were recorded in the Hibidex DAP® group (tooth and filling staining 9.5% and 4.74% respectively, transitory tongue numbness 28.6% and reduced taste sensation 14.3%, were registered in the group of subjects using Ozosept® solution. Conclusion. It is concluded that Ozosept® solution is effective in the control of dental plaque - biofilm accumulation and gingival inflammation, and produces no side effects related to chlorhexidine digluconate usage.

  10. Current status of vulnerable plaque detection.

    LENUS (Irish Health Repository)

    Sharif, Faisal

    2012-02-01

    Critical coronary stenoses have been shown to contribute to only a minority of acute coronary syndromes (ACS) and sudden cardiac death. Autopsy studies have identified a subgroup of high-risk patients with disrupted vulnerable plaque and modest stenosis. Consequently, a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease. Recent advances in invasive and noninvasive imaging techniques have shown the potential to identify these high-risk plaques. The anatomical characteristics of the vulnerable plaque such as thin cap fibroatheroma and lipid pool can be identified with angioscopy, high frequency intravascular ultrasound, intravascular MRI, and optical coherence tomography. Efforts have also been made to recognize active inflammation in high-risk plaques using intravascular thermography. Plaque chemical composition by measuring electromagnetic radiation using spectroscopy is also an emerging technology to detect vulnerable plaques. Noninvasive imaging with MRI, CT, and PET also holds the potential to differentiate between low and high-risk plaques. However, at present none of these imaging modalities are able to detect vulnerable plaque neither has been shown to definitively predict outcome. Nevertheless in contrast, there has been a parallel development in the physiological assessment of advanced atherosclerotic coronary artery disease. Thus recent trials using fractional flow reserve in patients with modest non flow-limiting stenoses have shown that deferral of PCI with optimal medical therapy in these patients is superior to coronary intervention. Further trials are needed to provide more information regarding the natural history of high-risk but non flow-limiting plaque to establish patient-specific targeted therapy and to refine plaque stabilizing strategies in the future.

  11. A Review on Atherosclerotic Biology, Wall Stiffness, Physics of Elasticity, and Its Ultrasound-Based Measurement.

    Science.gov (United States)

    Patel, Anoop K; Suri, Harman S; Singh, Jaskaran; Kumar, Dinesh; Shafique, Shoaib; Nicolaides, Andrew; Jain, Sanjay K; Saba, Luca; Gupta, Ajay; Laird, John R; Giannopoulos, Argiris; Suri, Jasjit S

    2016-12-01

    Functional and structural changes in the common carotid artery are biomarkers for cardiovascular risk. Current methods for measuring functional changes include pulse wave velocity, compliance, distensibility, strain, stress, stiffness, and elasticity derived from arterial waveforms. The review is focused on the ultrasound-based carotid artery elasticity and stiffness measurements covering the physics of elasticity and linking it to biological evolution of arterial stiffness. The paper also presents evolution of plaque with a focus on the pathophysiologic cascade leading to arterial hardening. Using the concept of strain, and image-based elasticity, the paper then reviews the lumen diameter and carotid intima-media thickness measurements in combined temporal and spatial domains. Finally, the review presents the factors which influence the understanding of atherosclerotic disease formation and cardiovascular risk including arterial stiffness, tissue morphological characteristics, and image-based elasticity measurement.

  12. Blood pressure is the major driving force for plaque formation in aortic-constricted ApoE-/- mice

    DEFF Research Database (Denmark)

    Johansson, Maria E.; Wickman, Anna; Skøtt, Ole

    2006-01-01

    of a suprarenal silver clip around the aorta (AoC). Half the group was treated with the selective AT1 receptor antagonist losartan (30 mg/kg per day) for 4 weeks. RESULTS: Anesthetized mean arterial pressure (MAP) was increased in AoC mice compared to sham (106 +/- 3 versus 90 +/- 1 mmHg, P Losartan...... reduced MAP in sham mice (78 +/- 2 mmHg, P losartan 104 +/- 2 mmHg). Plasma renin concentration (PRC) was increased in AoC mice compared to sham [1.6 +/- 0.3 versus 0.8 +/- 0.2 milliGoldblatt units (mGU)/ml, P Losartan treatment augmented this difference (18.7 +/- 3.......09 versus 0.07 +/- 0.01%, P losartan did not alter plaque area. CONCLUSIONS: Our data do not support a role for the AT1 receptor in the progression of atherosclerosis in this model, since blockade with losartan did not alter plaque distribution. Furthermore, we found no support...

  13. Impact of the Daily Use of a Microcrystal Hydroxyapatite Dentifrice on De Novo Plaque Formation and Clinical/Microbiological Parameters of Periodontal Health. A Randomized Trial

    Science.gov (United States)

    Schlagenhauf, Ulrich; May, Theodor W.; Gravemeier, Martina; Prior, Karola; Petersilka, Gregor; Ehmke, Benjamin

    2016-01-01

    Aim This 12-week prospective, randomized, double-blind, two-center trial evaluated the impact of a microcrystalline zinc hydroxyapatite (mHA) dentifrice on plaque formation rate (PFR) in chronic periodontitis patients. We hypothesized that mHA precipitates cause delayed plaque development when compared to a fluoridated control (AmF/SnF2), and therefore would improve periodontal health. Material & Methods At baseline and after 4 and 12 weeks, PFR and other clinical and microbiological parameters were recorded. Seventy periodontitis patients received a mHA or AmF/SnF2 dentifrice as daily oral care without hygiene instructions. Four weeks after baseline, participants received full mouth debridement and continued using the dentifrices for another 8 weeks. Results Primary outcome PFR did not change statistically significantly from baseline to weeks 4 and 12, neither in mHA (n = 33; 51.7±17.2% vs. 48.5±16.65% vs. 48.4±19.9%) nor in AmF/SnF2-group (n = 34; 52.3±17.5% vs. 52.5±21.3% vs. 46.1±21.8%). Secondary clinical parameters such as plaque control record, gingival index, bleeding on probing, and pocket probing depth improved, but between-group differences were not statistically significant. Microbiological analyses showed similar slight decreases in colony-forming units in both groups. Conclusion In patients with mild-to-moderate periodontitis, periodontal therapy and use of a mHA-or AmF/SnF2 dentifrice without instructions induced comparable improvements in periodontal health but did not significantly reduce the PFR. Trial Registration ClincalTrials.gov NCT02697539 PMID:27467683

  14. ROCK1 is associated with Alzheimer’s disease-specific plaques, as well as enhances autophagosome formation but not autophagic Aβ clearance

    Directory of Open Access Journals (Sweden)

    Yong-Bo Hu

    2016-11-01

    Full Text Available Alzheimer’s disease (AD is the most prevalent form of late-life dementia in the population, characterised by amyloid plaque formation and increased tau deposition, which is modulated by Rho-associated coiled-coil kinase 1 (ROCK1. In this study, we further analyse whether ROCK1 regulates the metabolism of amyloid precursor protein (APP. We show that ROCK1 is colocalised with mature Aβ plaques in patients with AD, in that ROCK1 enhances the amyloidogenic pathway, and that ROCK1 mediated autophagy enhances the intracellular buildup of Aβ in a cell model of AD, (confirmed by increased ROCK1 and decreased Beclin 1 protein levels, with neuronal autophagosome accumulation in prefrontal cortex of AD APP/PS1 mouse model. In vitro over-expression of ROCK1 leads to a decrease in Aβ secretion and an increase in the expression of autophagy-related molecules. ROCK1 interacts with Beclin1, an autophagy initiator, and enhances the intracellular accumulation of Aβ. Reciprocally, overexpression of APP/Aβ promotes ROCK1 expression. Our data suggest ROCK1 participates in regulating Aβ secretion, APP shedding and autophagosome accumulation, and that ROCK1, rather than other kinases, is more likely to be a targetable enzyme for AD therapy.

  15. The reduction of aorta histopathological images through inhibition of reactive oxygen species formation in hypercholesterolemia rattus norvegicus treated with polysaccharide peptide of Ganoderma lucidum

    Directory of Open Access Journals (Sweden)

    Titin Andri Wihastuti

    2015-05-01

    Full Text Available Objective(s:Atherosclerosis is chronic inflammatory process triggered by oxidative stress. Oxidative stress can increase hydrogen peroxide (H2O2level, which induce atherosclerosis through the processes such as formation of perivascular adipose tissue (PVAT, foam cells, and atherosclerotic plaque. Antioxidant is needed to control negative effects of oxidative stress. One source of antioxidant, which has potential to be developed, is PsP from Ganoderma lucidum. This study aims to prove the effect of PsP in decreasing H2O2, PVAT, foam cells and atherosclerotic plaque. Materials and Methods: This study was experimental randomized post-test with control group design using 25 Rattus norvegicus Wistar strain rats. Rats were divided into 5 groups (negative control, positive control, and 3 high-fat diet group with PsP dose: 50, 150, 300 mg/kgBW. Measured parameters were H2O2, PVAT, foam cell, and atherosclerotic plaques. Analysis of variance (ANOVA was used for statistical analysis, followed by post hoc test. Results: Mean H2O2 levels, PVAT thickness, foam cell numbers, and atherosclerotic plaque were low in negative control group. ANOVA showed that PsP significantly (P

  16. Spiral computed tomographic imaging related to computerized ultrasonographic images of carotid plaque morphology and histology

    DEFF Research Database (Denmark)

    Grønholdt, Marie-Louise; Wagner, A; Wiebe, B M

    2001-01-01

    Echolucency of carotid atherosclerotic plaques, as evaluated by computerized B-mode ultrasonographic images, has been associated with an increased incidence of brain infarcts on cerebral computed tomographic scans. We tested the hypotheses that characterization of carotid plaques on spiral comput...

  17. Monocyte Adhesion and Plaque Recruitment During Atherosclerosis Development Is Regulated by the Adapter Protein Chat-H/SHEP1.

    Science.gov (United States)

    Herbin, Olivier; Regelmann, Adam G; Ramkhelawon, Bhama; Weinstein, Erica G; Moore, Kathryn J; Alexandropoulos, Konstantina

    2016-09-01

    The chronic inflammation associated with atherosclerosis is caused by lipid deposition followed by leukocyte recruitment to the arterial wall. We previously showed that the hematopoietic cell-specific adaptor protein Cas- and Hef1-associated signal transducer hematopoietic isoform (Chat-H)/SHEP1 regulated lymphocyte adhesion and migration. In this study, we analyzed the role of Chat-H in atherosclerosis development. Using Chat-H-deficient bone marrow transplantation in low-density lipoprotein receptor-deficient mice, we found that Chat-H regulated atherosclerotic plaque formation. Chat-H deficiency in hematopoietic cells associated with lower plaque complexity and fewer leukocytes in the lesions, whereas myeloid-specific deletion of Chat-H was sufficient for conferring atheroprotection. Chat-H deficiency resulted in reduced recruitment of classical Ly6c(high) and nonclassical Ly6c(low) monocytes to the plaques, which was accompanied by increased numbers of both monocyte subsets in the blood. This associated with defective adhesion of Chat-H-deficient Ly6c(high) and Ly6c(low) monocytes to vascular cell adhesion molecule-1 in vitro and impaired infiltration of fluorescent bead-loaded monocytes to atherosclerotic plaques. In contrast, Chat-H was dispensable for CX3CL1 and CCR1/CCR5-dependent migration of monocytes. Our findings highlight Chat-H as a key protein that regulates atherosclerosis development by controlling monocyte adhesion and recruitment to the plaques and identify a novel target that may be exploited for treating atherosclerosis. © 2016 American Heart Association, Inc.

  18. Intracranial Atherosclerotic Disease

    Directory of Open Access Journals (Sweden)

    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.

  19. Residual plaque burden, delivered dose, and tissue composition predict 6-month outcome after balloon angioplasty and beta-radiation therapy

    NARCIS (Netherlands)

    M. Sabaté (Manel); J.P. Marijnissen (Johannes); S.G. Carlier (Stephan); I.P. Kay (Ian Patrick); V.L.M.A. Coen (Veronique); J.M.R. Ligthart (Jürgen); M.A. Costa (Marco); P.W.J.C. Serruys (Patrick); P.C. Levendag (Peter); W.J. van der Giessen (Wim); H. Boersma (Eric)

    2000-01-01

    textabstractBACKGROUND: Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary

  20. Modeling of drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls to treat vulnerable plaques

    KAUST Repository

    Hossain, Shaolie S.

    2010-01-01

    The main objective of this work is to develop computational tools to support the design of a catheter-based local drug delivery system that uses nanoparticles as drug carriers in order to treat vulnerable plaques and diffuse atherosclerotic disease.

  1. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages

    NARCIS (Netherlands)

    Sanchez-Gaytan, Brenda L.; Fay, Francois; Lobatto, Mark E.; Tang, Jun; Ouimet, Mireille; Kim, Yongtae; van der Staay, Susanne E. M.; van Rijs, Sarian M.; Priem, Bram; Zhang, Liangfang; Fisher, Edward A.; Moore, Kathryn J.; Langer, Robert; Fayad, Zahi A.; Mulder, Willem J. M.

    2015-01-01

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and

  2. Intravascular palpography for high-risk vulnerable plaque assessment.

    NARCIS (Netherlands)

    Schaar, J.A.; Korte, C.L. de; Mastik, F.; Baldewsing, R.A.; Regar, E.; Feyter, P. de; Slager, C.J.; Steen, A.F.W. van der; Serruys, P.W.

    2003-01-01

    BACKGROUND: The composition of an atherosclerotic plaque is considered more important than the degree of stenosis. An unstable lesion may rupture and cause an acute thrombotic reaction. Most of these lesions contain a large lipid pool covered by an inflamed thin fibrous cap. The stress in the cap

  3. 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, Søren Høyer; 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...

  4. [Prognostic assessment for formation of a group of cardiovascular high risk among personnel participating in atomic submarines utilization].

    Science.gov (United States)

    Sosiukin, A E; Vasiliuk, V B; Ivanchenko, A V; Saenko, S A; Semenchuk, O A; Dokhov, M A; Verveda, A B

    2014-01-01

    Ultrasound scanning of main vessels (common carotid, internal carotid, common and superficial femoral, posterior tibial arteries) in staffers of shipyard "Nerpa"--branch of JSC "Shipbuilding center Zvezdochka" (Snezhnogorsk city Murmansk region)--engaged into atomic submarines utilization. Findings are atherosclerotic changes in common carotid and common femoral arteries--increased thickness of intima-media complex over the reference values or atherosclerotic plaque formation. The changes were maximal in a group of males aged over 50 with length of service over 25 years. Discriminant analysis helped to suggest a mathematic model to forecast cardiovascular diseases in personnel of "Nerpa" shipyard.

  5. Ultrasound Vascular Elastography as a Tool for Assessing Atherosclerotic Plaques

    DEFF Research Database (Denmark)

    Mahmood, Badar; Ewertsen, C; Carlsen, Jørn

    2016-01-01

    Library and Web of Science databases. A standardized template was used to extract relevant data following the PRISMA 2009 checklist. 20 articles were included in this paper. The studies were heterogeneous. All studies reported that elastography was a feasible technique and provided additional information...

  6. Exploring the complex biology of the carotid atherosclerotic plaque

    NARCIS (Netherlands)

    Siemelink, MA

    2016-01-01

    Cardiovascular disease (CVD) as result of atherosclerosis is a major cause of morbidity and mortality in many societies, despite the enormous research efforts in recent decades directed at prevention and improved treatment. Atherosclerosis of blood vessels can result in life threatening health

  7. Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.

    Science.gov (United States)

    Singh, Vishal; Rana, Minakshi; Jain, Manish; Singh, Niharika; Naqvi, Arshi; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

    2015-01-14

    In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1β and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-β (TGF-β) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the expression of TGF-β in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1β and increased the levels of TGF-β. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

  8. Effect of calcification on the mechanical stability of plaque based on a three-dimensional carotid bifurcation model

    Directory of Open Access Journals (Sweden)

    Wong Kelvin KL

    2012-02-01

    Full Text Available Abstract Background This study characterizes the distribution and components of plaque structure by presenting a three-dimensional blood-vessel modelling with the aim of determining mechanical properties due to the effect of lipid core and calcification within a plaque. Numerical simulation has been used to answer how cap thickness and calcium distribution in lipids influence the biomechanical stress on the plaque. Method Modelling atherosclerotic plaque based on structural analysis confirms the rationale for plaque mechanical examination and the feasibility of our simulation model. Meaningful validation of predictions from modelled atherosclerotic plaque model typically requires examination of bona fide atherosclerotic lesions. To analyze a more accurate plaque rupture, fluid-structure interaction is applied to three-dimensional blood-vessel carotid bifurcation modelling. A patient-specific pressure variation is applied onto the plaque to influence its vulnerability. Results Modelling of the human atherosclerotic artery with varying degrees of lipid core elasticity, fibrous cap thickness and calcification gap, which is defined as the distance between the fibrous cap and calcification agglomerate, form the basis of our rupture analysis. Finite element analysis shows that the calcification gap should be conservatively smaller than its threshold to maintain plaque stability. The results add new mechanistic insights and methodologically sound data to investigate plaque rupture mechanics. Conclusion Structural analysis using a three-dimensional calcified model represents a more realistic simulation of late-stage atherosclerotic plaque. We also demonstrate that increases of calcium content that is coupled with a decrease in lipid core volume can stabilize plaque structurally.

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

    DEFF Research Database (Denmark)

    Pedersen, Sune F; Ludvigsen, Trine Pagh; 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-induc...

  10. 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

  11. Vulnerable Plaques, Inflammation and Newer Imaging Modalities

    Directory of Open Access Journals (Sweden)

    Bhatia V

    2003-01-01

    Full Text Available Currently, inflammation is considered to be the central player in the pathogenesis of atherosclerosis. It leads to the formation of multiple plaques in the arterial beds including coronary vasculature. Recent studies using the latest imaging techniques have shown that in patients with acute coronary syndromes (ACS multiple plaques are ruptured and have thrombus formation on them. Various factors make these plaques unstable, these include structural components of plaque like thin fibrous cap, high lipid content of the plaque core and inflammation, both localized and generalized. It has been shown that most of the ACS are caused by plaques causing non-critical stenosis as seen on traditional X-ray angiography. Also, the phenomenon of remodelling makes angiography a poor technique for plaque visualization. Hence newer modalities are required to identify these 'vulnerable plaques'. Intravascular ultrasound (IVUS, thermography and Magnetic Resonance Imaging (MRI are a few such promising techniques. Here we review the invasive and non-invasive modalities that can be helpful in the identification of these plaques before they become unstable and cause ACS, and also the available therapies to stabilize these plaques.

  12. Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

    Science.gov (United States)

    Kovanen, Petri T; Bot, Ilze

    2017-10-12

    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.

  13. Experience With Intravascular Ultrasound Imaging Of Human Atherosclerotic Arteries

    Science.gov (United States)

    Mallery, John A.; Gessert, James M.; Maciel, Mario; Tobis, John M.; Griffith, James M.; Berns, Michael W.; Henry, Walter L.

    1989-08-01

    Normal human arteries have a well-defined structure on intravascular images. The intima appears very thin and is most likely represented by a bright reflection arising from the internal elastic lamina. The smooth muscle tunica media is echo-lucent on the ultrasound image and appears as a dark band separating the intima from the adventitia. The adventitia is a brightly reflective layer of variable thickness. The thickness of the intima, and therefore of the atherosclerotic plaque can be accurately measured from the ultrasound images and correlates well with histology. Calcification within the wall of arteries is seen as bright echo reflection with shadowing of the peripheral wall. Fibrotic regions are highly reflective but do not shadow. Necrotic liquid regions within advanced atherosclerotic plaques are seen on ultrasound images as large lucent zones surrounded by echogenic tissue. Imaging can be performed before and after interventional procedures, such as laser angioplasty, balloon angioplasty and atherectomy. Intravascular ultrasound appears to provide an imaging modality for identifying the histologic characteristics of diseased arteries and for quantifying plaque thickness. It might be possible to perform such quantification to evaluate the results of interventional procedures.

  14. New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-κB pathway.

    Science.gov (United States)

    Tang, Zhi-Han; Peng, Juan; Ren, Zhong; Yang, Jing; Li, Ting-Ting; Li, Tao-Hua; Wang, Zuo; Wei, Dang-Heng; Liu, Lu-Shan; Zheng, Xi-Long; Jiang, Zhi-Sheng

    2017-07-01

    Proprotein convertase subtilisin/kexin 9 (PCSK9) has emerged as a popular target in the development of new cholesterol-lowering drugs and therapeutic interventions for atherosclerosis. PCSK9 could accelerate atherosclerosis through mechanisms beyond the degradation of the hepatic low-density lipoprotein receptor. Several clinical studies suggested that PCSK9 is involved in atherosclerotic inflammation. Accordingly, this study aimed to explore the role of PCSK9 in vascular inflammation that promotes atherosclerotic progression. We examined whether PCSK9 silencing via transduction with the lentivirus-mediated PCSK9 shRNA (LV-PCSK9 shRNA) vector affects the formation of vascular lesions in hyperlipidemia-induced atherosclerosis in apolipoprotein E knockout (apoE KO) mice. In vitro, the effects of PCSK9 on oxLDL-induced macrophages inflammation were investigate using LV-PCSK9 and LV-PCSK9 shRNA for PCSK9 overexpression and PCSK9 silencing. Immunohistochemical analysis showed that PCSK9 expression increased within atherosclerotic plaques in apoE KO mice. These in vivo results showed that the LV-PCSK9 shRNA group of mice developed less aortic atherosclerotic plaques compared with the control group. These lesions also had the reduced number of macrophages and decreased expression of vascular inflammation regulators, such as tumor necrosis factor-α, interleukin 1 beta, monocyte chemoattractant protein-1, toll-like receptor 4 and nuclear factor kappa B (NF-κB). We further showed that PCSK9 overexpression in macrophages in vitro increased the secretion of oxLDL-induced proinflammatory cytokines. PCSK9 overexpression upregulated TLR4 expression and increased p-IκBα levels, IkBα degradation, and NF-κB nuclear translocation in macrophages, but PCSK9 knockdown had the opposite effects in oxLDL-treated macrophages. PCSK9 gene interference could suppress atherosclerosis directly through decreasing vascular inflammation and inhibiting the TLR4/NF-κB signaling pathway without

  15. Multiple yellow plaques assessed by angioscopy with quantitative colorimetry in patients with myocardial infarction.

    Science.gov (United States)

    Inami, Shigenobu; Ishibashi, Fumiyuki; Waxman, Sergio; Okamatsu, Kentaro; Seimiya, Koji; Takano, Masamichi; Uemura, Ryota; Sano, Junko; Mizuno, Kyoichi

    2008-03-01

    Multiple angioscopic yellow plaques are associated with diffuse atherosclerotic plaque, and may be prevalent in patients with myocardial infarction (MI), so in the present study the yellow plaques in the coronary arteries of patients with MI was evaluated using quantitative colorimetry, and compared with those of patients with stable angina (SA). In the recorded angioscopic images of 3 coronary vessels in 29 patients (15 patients with MI, 14 with SA), yellow plaques were determined as visually yellow regions with b* value >0 (yellow color intensity) measured by the quantitative colorimetric method. A total of 90 yellow plaques were identified (b* =19.35+/-8.3, 3.05-45.35). Yellow plaques were significantly more prevalent in 14 (93%) of 15 culprit lesions of MI as compared with 8 (57%) of 14 of SA (p=0.03). In non-culprit segments, yellow plaques were similarly prevalent in 13 (87%) patients with MI and 11 (79%) with SA (p=0.65). Overall, multiple (> or =2) yellow plaques were prevalent in 13 (87%) patients with MI, similar to the 10 (71%) with SA (p=0.38). The number of yellow plaques was significantly higher in patients with MI (3.8+/-1.9) than in those with SA (2.4+/-1.6, p=0.03). The present study suggests that patients with MI tend to have diffuse atherosclerotic plaque in their coronary arteries.

  16. Reducing dental plaque formation and caries development. A review of current methods and implications for novel pharmaceuticals.

    Science.gov (United States)

    Kalesinskas, Povilas; Kačergius, Tomas; Ambrozaitis, Arvydas; Pečiulienė, Vytautė; Ericson, Dan

    2014-01-01

    Dental caries is an oral disease, which has a high worldwide prevalence despite the availability of various prophylactic means, including the daily use of fluoride toothpastes, water fluoridation, dental sealants, oral health educational programs and various antiseptic mouth-rinses. One important reason for this is uncontrolled increase in consumption of foods containing considerable sucrose concentration, especially among children. Sucrose is easily metabolized by oral bacteria (mostly streptococci) to acids and, subsequently, causing tooth decay or dental caries. In the oral ecosystem, streptococci principally reside on tooth surfaces forming biofilm. Important structural and binding materials of biofilm are glucan polymers synthesized by several isoforms of glucosyltransferase enzyme present in certain species of oral bacteria, including mutans group streptococci - Streptococcus mutans and Streptococcus sobrinus, which preferably colonize humans. Thus, there is a constant need to develop the methods and chemotherapeutics for improving oral health care and decreasing teeth decay through the suppression of cariogenic biofilm formation in the oral cavity. The aim of this paper was to review literature related to the pathogenesis of dental caries as well as currently existing and experimental pharmaceutical substances used for prevention of this process.

  17. The unstable plaque: a diagnostic challenge in cardiology; Diagnostische Herausforderung in der Kardiologie: Die instabile arteriosklerotische Plaque

    Energy Technology Data Exchange (ETDEWEB)

    Levkau, B. [Inst. fuer Pathophysiologie, Universitaetsklinikum Essen (Germany); Schaefers, M. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Muenster (Germany)

    2004-09-01

    Atherosclerotic plaque rupture still accounts for one third of all deaths worldwide and constitutes a major source of disability and health care costs. Dysregulation of MMPs in the atherosclerotic lesion may result in mechanical destabilization and rupture of the atherosclerotic plaque, potentially leading to thrombosis and vessel occlusion with life-threatening clinical complications. Therefore, identifying individual patients at high risk of plaque rupture is an important challenge in clinical medicine. We have used the broad-spectrum MMP inhibitor CGS 27023A to develop the radioligand [{sup 123}I]I-HO-CGS 27023A for in vivo imaging of MMP activity. Using this radioligand, we were able to specifically image MMP activity by scintigraphy in vivo in the MMP-rich vascular lesions that develop after carotid artery ligation and cholesterol-rich diet in apolipoprotein E-deficient mice. Thus, imaging of MMP activity in vivo is feasible using radiolabelled MMP inhibitors. In combination with the high-resolution morphological imaging techniques such as MRI and CT, the molecular imaging of individual disease parameters such as MMP activity in lesions of atherosclerosis may help design approaches for the prediction and prevention of coronary events due to plaque rupture of an individual lesion in an individual patient. (orig.)

  18. When to image carotid plaque inflammation with FDG PET/CT

    DEFF Research Database (Denmark)

    Græbe, Martin; Borgwardt, Lise; Højgaard, Liselotte

    2010-01-01

    Quantification of 18-fluorodeoxyglucose (FDG) uptake in inflamed high-risk carotid atherosclerotic plaques is challenged by the spatial resolution of positron emission tomography (PET) and luminal blood activity. Late acquisition protocols have been used to overcome these challenges to enhance...... the contrast between the plaque and blood-pool FDG activity. However, for prospective studies the late acquisition is inconvenient for the patient and staff, and most retrospective studies of plaque uptake use data from early acquisition protocols. The objective was to evaluate changes in the quantification...... methods of FDG uptake in carotid artery plaques between early and late PET scans....

  19. The role of selected chemokines and their receptors in the pathogenesis and destabilisation of atheromatous plaques in the carotid arteries

    Directory of Open Access Journals (Sweden)

    Maria Konarska-Król

    2015-04-01

    Full Text Available Chemokines are cytokines that act selectively on cells and are capable of inducing selective migration of cells in vitro and in vivo. The term was first coined at the 3rd International Symposium on Chemotactic Cytokines in 1992. The name “chemokine” is a contraction of “chemotactic cytokine,” meaning that these molecules combine features of both cytokines and chemotactic factors. They are a family of low-molecular-mass proteins acting on specific membrane receptors. A cell’s overall sensitivity to chemotaxis depends on the expression profile of chemokine receptors. Atherosclerosis is essentially an excessive inflammatory and proliferative response to the damage of arterial walls. It takes place within the wall and leads to the formation of unstable atherosclerotic plaques. Many chemokines have been studied in terms of their role in the pathogenesis of an atheromatous plaque in the carotid arteries, both in animal models and with the use of human tissue. It  seems that molecules that are the most involved in the formation of atheromas in the carotid arteries include: CCL2, CCL3, CCL4 and CCL5. However, reports are sometimes contradictory, and more research is needed. Finding a marker that could help predict the destabilisation of an atheromatous plaque would be a valuable addition to the standard diagnostic panel of tests used in both the diagnosis and monitoring of vascular pathologies.

  20. Quantitative analysis of carotid plaque vasa vasorum by CEUS and correlation with histology after endarterectomy.

    Science.gov (United States)

    Vavuranakis, Manolis; Sigala, Fragiska; Vrachatis, Dimitrios A; Papaioannou, Theodore G; Filis, Konstantinos; Kavantzas, Nikolaos; Kalogeras, Konstantinos I; Massoura, Constantina; Toufektzian, Levon; Kariori, Maria G; Vlasseros, Ioannis; Kallikazaros, Ioannis; Stefanadis, Christodoulos

    2013-05-01

    Intraplaque neovascularization and vasa vasorum (VV) proliferation contribute in the progression and rupture of atherosclerotic lesions. Contrast enhanced ultrasonography (CEUS) has been reported to attain data regarding intraplaque neovessels and VV. However, whether the detection of microbubbles by CEUS within atherosclerotic plaques truly represents microvessels is a point of concern. We aimed to evaluate stable and unstable carotid artery plaque (CAP) VV pattern by CEUS and its correlation with histology and immunochemistry. Patients with CAP scheduled for plaque endarterectomy were enrolled. CAP was initially identified by conventional ultrasonography and subsequently CEUS (harmonic ultrasound imaging with simultaneous intravenous contrast agent injection) was performed. The recorded image loops were evaluated by a semi-automated method. Plaque specimens were excised and underwent histological and immunochemical (for CD34, Vascular Endothelial Growth Factor, CD68 and CD3 antibodies) analysis. Fourteen patients (67.6 ± 10.2 years, 10 males) with a 86.9 ± 11.5 % degree of carotid artery stenosis were evaluated. Histology showed that half of the plaques were unstable. Enhancement of plaque brightness on CEUS was significant for both stable and unstable plaque subgroups (p = 0.018 for both). Immunochemistry showed that microvessels, as assessed by CD34 antibody, were more dense in unstable vs. stable plaques (36.6 ± 17.4 vs. 13.0 ± 7.2 respectively, p = 0.002). However, correlation between plaque brigthness enhancement on CEUS and microvessel density was significant only for stable (r = 0.800, p = 0.031) plaques. The identification of brightness enhacement during CEUS in carotid atherosclerotic plaques may not always reflect the presence of VV.

  1. Denitrification in human dental plaque

    Directory of Open Access Journals (Sweden)

    Verstraete Willy

    2010-03-01

    Full Text Available Abstract Background Microbial denitrification is not considered important in human-associated microbial communities. Accordingly, metabolic investigations of the microbial biofilm communities of human dental plaque have focused on aerobic respiration and acid fermentation of carbohydrates, even though it is known that the oral habitat is constantly exposed to nitrate (NO3- concentrations in the millimolar range and that dental plaque houses bacteria that can reduce this NO3- to nitrite (NO2-. Results We show that dental plaque mediates denitrification of NO3- to nitric oxide (NO, nitrous oxide (N2O, and dinitrogen (N2 using microsensor measurements, 15N isotopic labelling and molecular detection of denitrification genes. In vivo N2O accumulation rates in the mouth depended on the presence of dental plaque and on salivary NO3- concentrations. NO and N2O production by denitrification occurred under aerobic conditions and was regulated by plaque pH. Conclusions Increases of NO concentrations were in the range of effective concentrations for NO signalling to human host cells and, thus, may locally affect blood flow, signalling between nerves and inflammatory processes in the gum. This is specifically significant for the understanding of periodontal diseases, where NO has been shown to play a key role, but where gingival cells are believed to be the only source of NO. More generally, this study establishes denitrification by human-associated microbial communities as a significant metabolic pathway which, due to concurrent NO formation, provides a basis for symbiotic interactions.

  2. [Atorvastatin inhibits the atherosclerotic lesion induced by tumor necrosis factor-like weak inducer of apoptosis in apolipoprotein E deficient mice].

    Science.gov (United States)

    Fernández-Laso, Valvanera; Sastre, Cristina; Egido, Jesús; Martín-Ventura, Jose L; Blanco-Colio, Luis M

    2015-01-01

    Interaction of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) with its receptor Fn14 accelerates atherosclerotic plaque development in ApoE deficient mice (ApoE KO). In this work, an analysis has been made on the effect of an HMG-CoA reductase inhibitor, atorvastatin, on atherosclerotic plaque development accelerated by TWEAK in ApoE KO mice. Eight week-old ApoE KO mice were fed with a high cholesterol diet for 4 weeks.