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Sample records for widespread atherosclerotic vascular

  1. Evaluation and percutaneous management of atherosclerotic peripheral vascular disease

    International Nuclear Information System (INIS)

    Widlus, D.M.; Osterman, F.A. Jr.

    1989-01-01

    Atherosclerotic peripheral vascular disease (PVD) of the lower extremities deprives a person of the ability to exercise to their satisfaction, later of the ability to perform the activities of their daily life, and finally of their legs themselves. Peripheral vascular disease has long been managed by the vascular surgeon utilizing endarterectomy and peripheral arterial bypass. Patient acceptance of nonsurgical, percutaneous procedures such as percutaneous transluminal balloon angioplasty (PTA) is high. Increased utilization of these procedures has led to improved techniques and adjuncts to therapy, as well as more critical review of long-term results. This article will review the evaluation and nonoperative management of PVD, with an emphasis on the newer modalities of management presently being investigated

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

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    Pavel Poredoš

    2012-02-01

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

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

    DEFF Research Database (Denmark)

    Deckert, T; Yokoyama, H; Mathiesen, E

    1996-01-01

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

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

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

    2015-01-01

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

  5. Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral vascular disease.

    LENUS (Irish Health Repository)

    Saeed, A

    2012-01-31

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  7. Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender

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    Pereira Thiago MC

    2010-08-01

    Full Text Available Abstract Background Although advanced age is considered a risk factor for several diseases, the impact of gender on age-associated cardiovascular diseases, such as atherosclerotic processes and valvular diseases, remains not completely clarified. The present study was designed to assess aortic valve morphology and function and vascular damage in elderly using the apolipoprotein E knockout (ApoE KO mouse. Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice. Methods The grade (0 to 4 of aortic regurgitation was evaluated through angiography. In addition, vascular lipid deposition and senescence were evaluated through histochemical analyses in aged male and female ApoE KO mice, and the results were compared to wild-type C57BL/6J (C57 mice. Results Aortic regurgitation was observed in 92% of the male ApoE KO mice and 100% of the male C57 mice. Comparatively, in age-matched female ApoE KO and C57 mice, aortic regurgitation was observed in a proportion of 58% and 53%, respectively. Histological analysis of the aorta showed an outward (positive remodeling in ApoE KO mice (female: 1.86 ± 0.15; male: 1.89 ± 0.68 using C57 groups as reference values. Histochemical evaluation of the aorta showed lipid deposition and vascular senescence only in the ApoE KO group, which were more pronounced in male mice. Conclusion The data show that male gender contributes to the progression of aortic regurgitation and that hypercholesterolemia and male gender additively contribute to the occurrence of lipid deposition and vascular senescence in elderly mice.

  8. 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

  9. Inflammation in renal atherosclerotic disease.

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    Udani, Suneel M; Dieter, Robert S

    2008-07-01

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

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

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

    2016-10-15

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

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

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

    2016-03-31

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

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

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

    2012-10-19

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

  13. Usefulness of 201Tl myocardial scintigraphy after dipyridamole infusion in patients with atherosclerotic vascular disease

    International Nuclear Information System (INIS)

    Toyama, Takuji; Nishimura, Tsunehiko; Uehara, Toshiisa

    1992-01-01

    To determine the utility for detecting ischemic heart disease (IHD), dipyridamole thallium myocardial images (DIP-Tl) have been performed in 103 patients with atherosclerotic vascular disease who can't exercise fully. Of the 103 patients, there were 36 patients with arteriosclerosis obliterans (ASO), 31 patients with aneurysm of the abdominal aorta (AAA), 24 patients with aneurysm of the thoracic aorta (TAA) and 12 patients with dissecting aortic aneurysm (DAA). Clinical evidence of IHD was found in 20 patients with ASO, 10 with AAA, 7 with TAA and 4 with DAA. Positive evidence of DIP-Tl was identified in 66% of 41 patients who had clinical evidence of IHD, and particularly in the patients with AAA (80%) and ASO (65%). On the other hand, in the patients without clinical evidence of IHD, positive evidence of DIP-Tl was identified in 19% of 62 patients and particularly in the patients with AAA (39%). In all patients, the percentage of the positive DIP-Tl ratio was 38%. And, when the 38% patients of the positive DIP-Tl were added to the patients of the negative DIP-Tl who had clinical evidence of IHD, almost half patients (51%) were considered to be complicated with IHD. This study suggests that the atherosclerotic vascular disease is highly complicated with IHD and DIP-Tl is useful to detect IHD. (author)

  14. Quantification of atherosclerotic plaque activity and vascular inflammation using [18-F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).

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    Mehta, Nehal N; Torigian, Drew A; Gelfand, Joel M; Saboury, Babak; Alavi, Abass

    2012-05-02

    Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC) and carotid intimal medial thickness (C-IMT) provide information about the burden of disease. However, despite multiple validation studies of CAC, and C-IMT, these modalities do not accurately assess plaque characteristics, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events. [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity, an important source of cellular inflammation in vessel walls. More recently, we and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors and is also highly associated with overall burden of atherosclerosis. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy as well as longer term therapeutic lifestyle changes (16 months). The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is

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

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    Tanasković Irena

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    Echeverry, Dario; Delgadillo, Alexandra; Montes, Felix

    2007-01-01

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

  17. Associations of cardiovascular risk factors, carotid intima-media thickness and manifest atherosclerotic vascular disease with carpal tunnel syndrome

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    Liira Helena

    2011-04-01

    Full Text Available Abstract Background The role of atherosclerosis in carpal tunnel syndrome (CTS has not previously been addressed in population studies. The aim of this study was to investigate the associations of cardiovascular risk factors, carotid artery intima-media thickness (IMT, and clinical atherosclerotic diseases with CTS. Methods In this cross sectional study, the target population consisted of subjects aged 30 or over who had participated in the national Finnish Health Survey in 2000-2001. Of the 7977 eligible subjects, 6254 (78.4% were included in our study. Carotid IMT was measured in a sub-sample of subjects aged 45 to 74 (N = 1353. Results Obesity (adjusted odds ratio (OR 2.4, 95% confidence interval (CI 1.1-5.4, high LDL cholesterol (OR 3.8, 95% CI 1.6-9.1 for >190 vs. 200 vs. Conclusions Our findings suggest an association between CTS and cardiovascular risk factors in young people, and carotid IMT and clinical atherosclerotic vascular disease in older people. CTS may either be a manifestation of atherosclerosis, or both conditions may share similar risk factors.

  18. Cardiovascular magnetic resonance in carotid atherosclerotic disease

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    Chen Huijun

    2009-12-01

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

  19. Lipidomics in vascular health: current perspectives.

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    Kolovou, Genovefa; Kolovou, Vana; Mavrogeni, Sophie

    2015-01-01

    Identifying the mechanisms that convert a healthy vascular wall to an atherosclerotic wall is of major importance since the consequences may lead to a shortened lifespan. Classical risk factors (age, smoking, obesity, diabetes mellitus, hypertension, and dyslipidemia) may result in the progression of atherosclerotic lesions by processes including inflammation and lipid accumulation. Thus, the evaluation of blood lipids and the full lipid complement produced by cells, organisms, or tissues (lipidomics) is an issue of importance. In this review, we shall describe the recent progress in vascular health research using lipidomic advances. We will begin with an overview of vascular wall biology and lipids, followed by a short analysis of lipidomics. Finally, we shall focus on the clinical implications of lipidomics and studies that have examined lipidomic approaches and vascular health.

  20. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

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    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.)

  1. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

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    Rosa Sessa

    2013-07-01

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

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

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    Lindholt Jes S

    2003-09-01

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

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

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    Soo-Jung Kim

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  6. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  8. Identification of chemical components of combustion emissions that affect pro-atherosclerotic vascular responses in mice.

    Science.gov (United States)

    Seilkop, Steven K; Campen, Matthew J; Lund, Amie K; McDonald, Jacob D; Mauderly, Joe L

    2012-04-01

    Combustion emissions cause pro-atherosclerotic responses in apolipoprotein E-deficient (ApoE/⁻) mice, but the causal components of these complex mixtures are unresolved. In studies previously reported, ApoE⁻/⁻ mice were exposed by inhalation 6 h/day for 50 consecutive days to multiple dilutions of diesel or gasoline exhaust, wood smoke, or simulated "downwind" coal emissions. In this study, the analysis of the combined four-study database using the Multiple Additive Regression Trees (MART) data mining approach to determine putative causal exposure components regardless of combustion source is reported. Over 700 physical-chemical components were grouped into 45 predictor variables. Response variables measured in aorta included endothelin-1, vascular endothelin growth factor, three matrix metalloproteinases (3, 7, 9), metalloproteinase inhibitor 2, heme-oxygenase-1, and thiobarbituric acid reactive substances. Two or three predictors typically explained most of the variation in response among the experimental groups. Overall, sulfur dioxide, ammonia, nitrogen oxides, and carbon monoxide were most highly predictive of responses, although their rankings differed among the responses. Consistent with the earlier finding that filtration of particles had little effect on responses, particulate components ranked third to seventh in predictive importance for the eight response variables. MART proved useful for identifying putative causal components, although the small number of pollution mixtures (4) can provide only suggestive evidence of causality. The potential independent causal contributions of these gases to the vascular responses, as well as possible interactions among them and other components of complex pollutant mixtures, warrant further evaluation.

  9. Collagen and related extracellular matrix proteins in atherosclerotic plaque development.

    Science.gov (United States)

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

    2014-10-01

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

  10. The surface chemistry determines the spatio-temporal interaction dynamics of quantum dots in atherosclerotic lesions.

    Science.gov (United States)

    Uhl, Bernd; Hirn, Stephanie; Mildner, Karina; Coletti, Raffaele; Massberg, Steffen; Reichel, Christoph A; Rehberg, Markus; Zeuschner, Dagmar; Krombach, Fritz

    2018-03-01

    To optimize the design of nanoparticles for diagnosis or therapy of vascular diseases, it is mandatory to characterize the determinants of nano-bio interactions in vascular lesions. Using ex vivo and in vivo microscopy, we analyzed the interactive behavior of quantum dots with different surface functionalizations in atherosclerotic lesions of ApoE-deficient mice. We demonstrate that quantum dots with different surface functionalizations exhibit specific interactive behaviors with distinct molecular and cellular components of the injured vessel wall. Moreover, we show a role for fibrinogen in the regulation of the spatio-temporal interaction dynamics in atherosclerotic lesions. Our findings emphasize the relevance of surface chemistry-driven nano-bio interactions on the differential in vivo behavior of nanoparticles in diseased tissue.

  11. Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression.

    Directory of Open Access Journals (Sweden)

    Kevin J Woollard

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

  12. 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.

  13. Metalloproteinases and atherothrombosis: MMP-10 mediates vascular remodeling promoted by inflammatory stimuli.

    Science.gov (United States)

    Rodriguez, Jose A; Orbe, Josune; Martinez de Lizarrondo, Sara; Calvayrac, Olivier; Rodriguez, Cristina; Martinez-Gonzalez, Jose; Paramo, Jose A

    2008-01-01

    Atherosclerosis is the common pathophysiological substrate of ischemic vascular diseases and their thrombotic complications. The unbalance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) has been hypothesized to be involved in the growth, destabilization, and eventual rupture of atherosclerotic lesions. Different MMPs have been assigned relevant roles in the pathology of vascular diseases and MMP-10 (stromelysin-2) has been involved in vascular development and atherogenesis. This article examines the pathophysiological role of MMPs, particularly MMP-10, in the onset and progression of vascular diseases and their regulation by pro-inflammatory stimuli. MMP-10 over-expression has been shown to compromise vascular integrity and it has been associated with aortic aneurysms. MMP-10 is induced by C-reactive protein in endothelial cells, and it is over-expressed in atherosclerotic lesions. Additionally, higher MMP-10 serum levels are associated with inflammatory markers, increased carotid intima-media thickness and the presence of atherosclerotic plaques. We have cloned the promoter region of the MMP-10 gene and studied the effect of inflammatory stimuli on MMP-10 transcriptional regulation, providing evidences further supporting the involvement of MMP-10 in the pathophysiology of atherothrombosis.

  14. Bilirubin and atherosclerotic diseases.

    Science.gov (United States)

    Vítek, L

    2017-04-05

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

  15. 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

  16. Systemic effects of periodontitis: Lessons learned from research on atherosclerotic vascular disease and adverse pregnancy outcomes

    Science.gov (United States)

    Papapanou, Panos N.

    2015-01-01

    Studies conducted over the past 25 years have focused on the role of periodontitis, an inflammatory condition of microbial etiology that destroys the tooth supporting tissues, as a systemic inflammatory stressor that can act as an independent risk factor of atherosclerotic vascular disease (AVSD) and adverse pregnancy outcomes (APOs). It has been suggested that periodontitis-associated bacteremias and systemic dissemination of inflammatory mediators produced in the periodontal tissues may result in systemic inflammation and endothelial dysfunction, while bacteria of oral origin may translocate into the feto-placental unit. Epidemiologic studies largely support an association between periodontitis and ASVD / APOs independent of known confounders; indeed, periodontitis has been shown to confer statistically significantly elevated risk for clinical events associated with ASVD and APOs in multivariable adjustments. On the other hand, intervention studies demonstrate that although periodontal therapy reduces systemic inflammation and improves endothelial function, it has no positive effect on the incidence of APOs. Studies of the effects of periodontal interventions on ASVD-related clinical events are lacking. This review summarizes key findings from mechanistic, association and intervention studies and attempts to reconcile the seemingly contradictory evidence that originates from different lines of investigation. PMID:26388299

  17. Amputation of extremity in patients with atherosclerotic gangrene

    Directory of Open Access Journals (Sweden)

    Tsareva Yu.O.

    2011-12-01

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

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

    Science.gov (United States)

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

    2011-07-01

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

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

    NARCIS (Netherlands)

    Verhoeven, B.A.N.

    2006-01-01

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

  20. Cellular Model of Atherogenesis Based on Pluripotent Vascular Wall Pericytes.

    Science.gov (United States)

    Ivanova, Ekaterina A; Orekhov, Alexander N

    2016-01-01

    Pericytes are pluripotent cells that can be found in the vascular wall of both microvessels and large arteries and veins. They have distinct morphology with long branching processes and form numerous contacts with each other and with endothelial cells, organizing the vascular wall cells into a three-dimensional network. Accumulating evidence demonstrates that pericytes may play a key role in the pathogenesis of vascular disorders, including atherosclerosis. Macrovascular pericytes are able to accumulate lipids and contribute to growth and vascularization of the atherosclerotic plaque. Moreover, they participate in the local inflammatory process and thrombosis, which can lead to fatal consequences. At the same time, pericytes can represent a useful model for studying the atherosclerotic process and for the development of novel therapeutic approaches. In particular, they are suitable for testing various substances' potential for decreasing lipid accumulation induced by the incubation of cells with atherogenic low-density lipoprotein. In this review we will discuss the application of cellular models for studying atherosclerosis and provide several examples of successful application of these models to drug research.

  1. The Interaction Between IGF-1, Atherosclerosis and Vascular Aging

    Science.gov (United States)

    Higashi, Yusuke; Quevedo, Henry C.; Tiwari, Summit; Sukhanov, Sergiy; Shai, Shaw-Yung; Anwar, Asif; Delafontaine, Patrice

    2014-01-01

    The process of vascular aging encompasses alterations in the function of endothelial (EC) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species (ROS) generation and inflammatory signaling, increased migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein-B containing low density lipoproteins resulting in activation of endothelial cells and recruitment of monocytes. Activated endothelial cells secrete “chemokines” that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a pro-inflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and non-vascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 (IGF-1) exerts anti-oxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability. PMID:24943302

  2. Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism

    NARCIS (Netherlands)

    Helgadottir, Anna; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Holm, Hilma; Patel, Riyaz S.; Gudnason, Thorarinn; Jones, Gregory T.; van Rij, Andre M.; Eapen, Danny J.; Baas, Annette F.; Tregouet, David-Alexandre; Morange, Pierre-Emmanuel; Emmerich, Joseph; Lindblad, Bengt; Gottsater, Anders; Kiemeny, Lambertus A.; Lindholt, Jes S.; Sakalihasan, Natzi; Ferrell, Robert E.; Carey, David J.; Elmore, James R.; Tsao, Philip S.; Grarup, Niels; Jorgensen, Torben; Witte, Daniel R.; Hansen, Torben; Pedersen, Oluf; Pola, Roberto; Gaetani, Eleonora; Magnadottir, Hulda B.; Wijmenga, Cisca; Tromp, Gerard; Ronkainen, Antti; Ruigrok, Ynte M.; Blankensteijn, Jan D.; Mueller, Thomas; Wells, Philip S.; Corral, Javier; Manuel Soria, Jose; Carlos Souto, Juan; Peden, John F.; Jalilzadeh, Shapour; Mayosi, Bongani M.; Keavney, Bernard; Strawbridge, Rona J.; Sabater-Lleal, Maria; Gertow, Karl; Baldassarre, Damiano; Nyyssonen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Tremoli, Elena; de Faire, Ulf; Humphries, Steve E.; Hamsten, Anders; Haraldsdottir, Vilhelmina; Olafsson, Isleifur; Magnusson, Magnus K.; Samani, Nilesh J.; Levey, Allan I.; Markus, Hugh S.; Kostulas, Konstantinos; Dichgans, Martin; Berger, Klaus; Kuhlenbaeumer, Gregor; Ringelstein, E. Bernd; Stoll, Monika; Seedorf, Udo; Rothwell, Peter M.; Powell, Janet T.; Kuivaniemi, Helena; Onundarson, Pall T.; Valdimarsson, Einar; Matthiasson, Stefan E.; Gudbjartsson, Daniel F.; Thorgeirsson, Guomundur; Quyyumi, Arshed A.; Watkins, Hugh; Farrall, Martin; Thorsteinsdottir, Unnur; Stefansson, Kari

    2012-01-01

    Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with

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

    Science.gov (United States)

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

    2007-02-01

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

  4. Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jun-ichi Kawabe

    2014-01-01

    Full Text Available Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process.

  5. Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study.

    Science.gov (United States)

    Kundel, Vaishnavi; Trivieri, Maria Giovanna; Karakatsanis, Nicolas A; Robson, Phillip M; Mani, Venkatesh; Kizer, Jorge R; Kaplan, Robert; Fayad, Zahi; Shah, Neomi

    2018-03-05

    Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging - hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer-before and after continuous positive airway pressure (CPAP). Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3-6 months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP. Five patients were recruited as part of a focused project. Mean age was 52 years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBR mean ) and 6.2% (TBR max ) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others). We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

  6. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    Science.gov (United States)

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  8. The effect of lowering LDL cholesterol on vascular access patency

    DEFF Research Database (Denmark)

    Herrington, William; Emberson, Jonathan; Staplin, Natalie

    2014-01-01

    BACKGROUND AND OBJECTIVES: Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with CKD, including dialysis patients, but the effect of lowering LDL-C on vascular access patency is unclear. DESIGN, SETTING, PARTICIPANTS...

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

    Directory of Open Access Journals (Sweden)

    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

  10. Mechanical properties of human atherosclerotic intima tissue.

    Science.gov (United States)

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

    2014-03-03

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

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

    Science.gov (United States)

    Orekhov, Alexander N

    2013-01-01

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

  12. CAROTID ATHEROSCLEROTIC LESION IN YOUNG PATIENTS

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    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.

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Directory of Open Access Journals (Sweden)

    C Soldani

    2009-06-01

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

  15. Anti-atherosclerotic effects of konjac

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2015-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Cinzia Parolini

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

  17. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

    DEFF Research Database (Denmark)

    Bowman, Louise; Hopewell, Jemma C; Chen, Fang

    2017-01-01

    vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per...

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

    Directory of Open Access Journals (Sweden)

    I. P. Dudanov

    2017-01-01

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

  19. Prognostic value of atherosclerotic burden and coronary vascular function in patients with suspected coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Assante, Roberta; Zampella, Emilia; Nappi, Carmela; Mainolfi, Ciro Gabriele; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Acampa, Wanda [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Arumugam, Parthiban; Tonge, Christine M. [Central Manchester University Teaching Hospitals, Nuclear Medicine Center, Manchester (United Kingdom); Gaudieri, Valeria; Panico, Mariarosaria; Magliulo, Mario [Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy)

    2017-12-15

    To evaluate the prognostic value of coronary atherosclerotic burden, assessed by coronary artery calcium (CAC) score, and coronary vascular function, assessed by coronary flow reserve (CFR) in patients with suspected coronary artery disease (CAD). We studied 436 patients undergoing hybrid {sup 82}Rb positron emission tomography/computed tomography imaging. CAC score was measured according to the Agatston method, and patients were categorized into three groups (0, <400, and ≥400). CFR was calculated as the ratio of hyperemic to baseline myocardial blood flow, and it was considered reduced when <2. Follow-up was 94% complete during a mean period of 47±15 months. During follow-up, 17 events occurred (4% cumulative event rate). Event-free survival decreased with worsening of CAC score category (p < 0.001) and in patients with reduced CFR (p < 0.005). At multivariable analysis, CAC score ≥400 (p < 0.01) and CFR (p < 0.005) were independent predictors of events. Including CFR in the prognostic model, continuous net reclassification improvement was 0.51 (0.14 in patients with events and 0.37 in those without). At classification and regression tree analysis, the initial split was on CAC score. For patients with a CAC score < 400, no further split was performed, while patients with a CAC score ≥400 were further stratified by CFR values. Decision curve analyses indicate that the model including CFR resulted in a higher net benefit across a wide range of decision threshold probabilities. In patients with suspected CAD, CFR provides significant incremental risk stratification over established cardiac risk factors and CAC score for prediction of adverse cardiac events. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Qin J

    2014-12-01

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

  1. 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.

  2. Anti-atherosclerotic effects of tomatoes

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2017-06-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  4. FY 1995 basic research to develop instruments for diagnosis of atherosclerosis on the basis of autofluorescence analysis of blood and vascular walls; 1995 nendo ketsueki oyobi kekkanheki no jiko keiko bunseki ni yoru domyaku koka shindan kiki kaiahtsu no tame no kisoteki kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    To obtain the basic data to develop instruments for diagnosis of atherosclerosis and to elucidate the mechanisms of atherogenesis by focusing on the autofluorescence of blood and vascular walls of atherosclerotic animal models and human patients. We have performed experiments to examine the relationships between autofluorescence of blood and vascular walls of guinea pig atherosclerotic model and human patients and obtained the following results. 1. The autofluorescence from human atherosclerotic aorta included the components with longer wave length than normal aorta, suggesting that diagnosis of atherosclerotic aortic walls will be possible using spectroscopic analysis through glass fiber catheter into vascular system. Further studies should be needed to the quantitative diagnosis. 2. The autofluorescence from blood plasma of human atherosclerotic patients has showed that the peak wave length was shorter than that of normal plasma. This phenomenon was mainly caused by the oxidization of plasma, especially lipoproteins, LDL and HDL. 3. Atherosclerotic model of the guinea pigs was quite similar to human atherosclerosis at the points of cholesterol levels and localization of lipid deposit to arterial walls, and showed to be useful for the studies of atherosclerosis. (NEDO)

  5. Identification of chemical components of combustion emissions that affect pro-atherosclerotic vascular responses in mice

    OpenAIRE

    Seilkop, Steven K.; Campen, Matthew J.; Lund, Amie K.; McDonald, Jacob D.; Mauderly, Joe L.

    2012-01-01

    Combustion emissions cause pro-atherosclerotic responses in apolipoprotein E-deficient (ApoE/−) mice, but the causal components of these complex mixtures are unresolved. In studies previously reported, ApoE−/− mice were exposed by inhalation 6 h/day for 50 consecutive days to multiple dilutions of diesel or gasoline exhaust, wood smoke, or simulated “downwind” coal emissions. In this study, the analysis of the combined four-study database using the Multiple Additive Regression Trees (MART) da...

  6. 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.

  7. Rapid noninvasive detection of experimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates

    Science.gov (United States)

    Elmaleh, David R.; Narula, Jagat; Babich, John W.; Petrov, Artiom; Fischman, Alan J.; Khaw, Ban-An; Rapaport, Eliezer; Zamecnik, Paul C.

    1998-01-01

    The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5′)-tetraphosphate) and its analogue 99mTc AppCHClppA for imaging experimental atherosclerotic lesions in New Zealand White rabbits. Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides. After acquiring the final images, the animals were sacrificed, ex vivo images of the aortas were recorded, and biodistribution was measured. 99mTc-Ap4A and 99mTc AppCHClppA accumulated rapidly in atherosclerotic abdominal aorta, and lesions were clearly visible within 30 min after injection in all animals that were studied. Both radiopharmaceuticals were retained in the lesions for 3 hr, and the peak lesion to normal vessel ratio was 7.4 to 1. Neither of the purine analogs showed significant accumulation in the abdominal aorta of normal (control) rabbits. The excised aortas showed lesion patterns that were highly correlated with the in vivo and ex vivo imaging results. The present study demonstrates that purine receptors are up-regulated in experimental atherosclerotic lesions and 99mTc-labeled purine analogs have potential for rapid noninvasive detection of plaque formation. PMID:9435254

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  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...... 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....

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Angiogenesis, Cancer, and Vascular Aging

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    Junji Moriya

    2017-10-01

    Full Text Available Several lines of evidence have revealed that the angiogenic response to ischemic injury declines with age, which might account for the increased morbidity and mortality of cardiovascular disease (CVD among the elderly. While impairment of angiogenesis with aging leads to delayed wound healing or exacerbation of atherosclerotic ischemic diseases, it also inhibits the progression of cancer. Age-related changes of angiogenesis have been considered to at least partly result from vascular aging or endothelial cell senescence. There is considerable evidence supporting the hypothesis that vascular cell senescence contributes to the pathogenesis of age-related CVD, suggesting that vascular aging could be an important therapeutic target. Since therapeutic angiogenesis is now regarded as a promising concept for patients with ischemic CVD, it has become even more important to understand the detailed molecular mechanisms underlying impairment of angiogenesis in older patients. To improve the usefulness of therapeutic angiogenesis, approaches are needed that can compensate for impaired angiogenic capacity in the elderly while not promoting the development or progression of malignancy. In this review, we briefly outline the mechanisms of angiogenesis and vascular aging, followed by a description of how vascular aging leads to impairment of angiogenesis. We also examine potential therapeutic approaches that could enhance angiogenesis and/or vascular function in the elderly, as well as discussing the possibility of anti-senescence therapy or reversal of endothelial cell senescence.

  12. 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.

  13. Circulating CD4+CD28null T Cells May Increase the Risk of an Atherosclerotic Vascular Event Shortly after Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Michiel G. H. Betjes

    2013-01-01

    Full Text Available Proinflammatory CD4+ T cells without the costimulatory molecule CD28 (CD4+CD28null T cells are expanded in patients with end-stage renal disease (ESRD and associated with atherosclerotic vascular events (AVE. In a prospective study, the number of circulating CD4+CD28null T cells was established in 295 ESRD patients prior to receiving a kidney allograft. Within the first year after transplantation, an AVE occurred in 20 patients. Univariate analysis showed that besides a history of cardiovascular disease (CVDpos, HR 8.1, , age (HR 1.04, , dyslipidaemia (HR 8.8, , and the % of CD4+CD28null T cells (HR 1.04 per % increase, 95% CI 1.00–1.09, were significantly associated with the occurrence of a posttransplantation AVE. In a multivariate analysis, only CVDpos remained a significant risk factor with a significant and positive interaction between the terms CVDpos and the % of CD4+CD28null T cells (HR 1.05, 95% CI 1.03–1.11, . Within the CVDpos group, the incidence of an AVE was 13% in the lowest tertile compared to 25% in the highest tertile of % of CD4+CD28null T cells. In conclusion, the presence of circulating CD4+CD28null T cells is associated with an increased risk for a cardiovascular event shortly after kidney transplantation.

  14. Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

    Science.gov (United States)

    Barton, Matthias; Husmann, Marc; Meyer, Matthias R

    2016-05-01

    Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  16. Effective risk stratification in patients with moderate cardiovascular risk using albuminuria and atherosclerotic plaques in the carotid arteries

    DEFF Research Database (Denmark)

    Greve, Sara V; Blicher, Marie K; Sehestedt, Thomas

    2015-01-01

    , Systematic COronary Risk Evaluation (SCORE), and Framingham risk score (FRS) groups. Subclinical vascular damage was defined as carotid-femoral pulse wave velocity at least 12 m/s, and carotid atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 90th percentile of 0.73/1.06 mg...... risk patients and high-intermediate FRS risk patients with high risk (P = 0.04 and P = 0.001, respectively), whereas elevated carotid-femoral pulse wave velocity did not. Elevated UACR or presence of atherosclerotic plaques reclassified patients from moderate to high SCORE risk [net reclassification...... improvement of 6.4%; P = 0.025), or from high intermediate to high FRS risk (net reclassification improvement 8.8%; P = 0.002). Assuming primary prevention could reduce the relative cardiovascular risk by 24-27%, on the basis of actual levels of blood pressure and cholesterol, one composite endpoint could...

  17. IGF-1 has plaque-stabilizing effects in atherosclerosis by altering vascular smooth muscle cell phenotype

    NARCIS (Netherlands)

    von der Thüsen, Jan H.; Borensztajn, Keren S.; Moimas, Silvia; van Heiningen, Sandra; Teeling, Peter; van Berkel, Theo J. C.; Biessen, Erik A. L.

    2011-01-01

    Insulin-like growth factor-1 (IGF-1) signaling is important for the maintenance of plaque stability in atherosclerosis due to its effects on vascular smooth muscle cell (vSMC) phenotype. To investigate this hypothesis, we studied the effects of the highly inflammatory milieu of the atherosclerotic

  18. Anti-Inflammatory Effects of Interleukin-19 in Vascular Disease

    Directory of Open Access Journals (Sweden)

    Ross N. England

    2012-01-01

    Full Text Available Despite aggressive dietary modification, lipid-lowering medications, and other interventional medical therapy, vascular disease continues to be a leading cause of mortality in the western world. It is a significant medical and socioeconomic problem contributing to mortality of multiple diseases including myocardial infarction, stroke, renal failure, and peripheral vascular disease. Morbidity and mortality of vascular disease are expected to worsen with the increasing number of patients with comorbid conditions such as obesity, metabolic syndrome, and diabetes mellitus type 2. Vascular diseases such as atherosclerosis, restenosis, and allograft vasculopathy are recognized to be driven by inflammation, and as such, cytokines which mediate inflammation not only represent important targets of rational therapy, but also can be considered as possible therapeutic modalities themselves. In this paper, we will examine the role of inflammatory cytokines and lymphocyte Th1/Th2 polarity in vascular inflammation, with a focus on atherosclerotic vascular disease. We will then introduce a recently described Th2 interleukin, interleukin-19 (IL-19, as a previously unrecognized mediator of vascular inflammatory disorders. We will review our current understanding of this interleukin in health and disease and present the possibility that IL-19 could represent a potential therapeutic to combat vascular inflammatory disease.

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

    Science.gov (United States)

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

    2008-01-01

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

  20. Widespread marrow necrosis during pregnancy

    International Nuclear Information System (INIS)

    Knickerbocker, W.J.; Quenville, N.F.

    1982-01-01

    Recently, a 22-year-old Caucasian female was referred to our Hospital two days post-partum. She had been feeling unwell during the last few days of her pregnancy and complained of multiple aches and pains, worst in the abdomen and lower back. Her admission platelet count was severely depressed and a bone biopsy showed extensive marrow necrosis with viable bony trabeculae. There was no evidence of vasculitis, vascular thrombosis, or malignancy. Widespread marrow necrosis in pregnancy followed by recovery, to our knowledge, has not been previously reported. (orig.)

  1. Impact of the cardiovascular system-associated adipose tissue on atherosclerotic pathology.

    Science.gov (United States)

    Chistiakov, Dimitry A; Grechko, Andrey V; Myasoedova, Veronika A; Melnichenko, Alexandra A; Orekhov, Alexander N

    2017-08-01

    Cardiac obesity makes an important contribution to the pathogenesis of cardiovascular disease. One of the important pathways of this contribution is the inflammatory process that takes place in the adipose tissue. In this review, we consider the role of the cardiovascular system-associated fat in atherosclerotic cardiovascular pathology and a non-atherosclerotic cause of coronary artery disease, such as atrial fibrillation. Cardiovascular system-associated fat not only serves as the energy store, but also releases adipokines that control local and systemic metabolism, heart/vascular function and vessel tone, and a number of vasodilating and anti-inflammatory substances. Adipokine appears to play an important protective role in cardiovascular system. Under chronic inflammation conditions, the repertoire of signaling molecules secreted by cardiac fat can be altered, leading to a higher amount of pro-inflammatory messengers, vasoconstrictors, profibrotic modulators. This further aggravates cardiovascular inflammation and leads to hypertension, induction of the pathological tissue remodeling and cardiac fibrosis. Contemporary imaging techniques showed that epicardial fat thickness correlates with the visceral fat mass, which is an established risk factor and predictor of cardiovascular disease in obese subjects. However, this correlation is no longer present after adjustment for other covariates. Nevertheless, recent studies showed that pericardial fat volume and epicardial fat thickness can probably serve as a better indicator for atrial fibrillation. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 3D Fiber Orientation in Atherosclerotic Carotid Plaques

    NARCIS (Netherlands)

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

    2017-01-01

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

  3. Rosuvastatin reduces atherosclerotic lesions and promotes progenitor cell mobilisation and recruitment in apolipoprotein E knockout mice.

    Science.gov (United States)

    Schroeter, Marco R; Humboldt, Tim; Schäfer, Katrin; Konstantinides, Stavros

    2009-07-01

    Statins enhance incorporation of bone marrow-derived cells into experimental neointimal lesions. However, the contribution of progenitor cells to progression of spontaneous atherosclerotic plaques, and the possible modulatory role of statins in this process, remain poorly understood. We compared the effects of rosuvastatin (1 and 10mg/kg BW) and pravastatin (10mg/kg) on progenitor cell mobilisation, recruitment into atherosclerotic plaques, and lesion growth. Statins were administered over 8 weeks to apolipoprotein E knockout mice on atherogenic diet. In addition, mice were lethally irradiated, followed by transplantation of bone marrow from LacZ transgenic mice. Rosuvastatin reduced lesion area and intima-to-media ratio at the brachiocephalic artery compared to vehicle, while both parameters were not significantly altered by pravastatin. Rosuvastatin also augmented endothelialisation (P<0.05) and reduced the smooth muscle cells (SMC) content (P=0.042) of lesions. Numbers of c-kit, sca-1 and flk-1, sca-1 double-positive progenitor cells were significantly increased in rosuvastatin compared to control-treated mice, both in the bone marrow and the peripheral blood. Similarly, the number of spleen-derived acLDL, lectin double-positive progenitor cells (P=0.001) and colony-forming units (P=0.0104) was significantly increased in mice treated with rosuvastatin compared to vehicle alone. In the bone marrow, increased Akt and p42/44 MAP kinase phosphorylation and upregulated SDF1alpha mRNA expression were observed. Importantly, rosuvastatin treatment also increased the plasma levels of c-kit ligand (P=0.003), and the number of c-kit-positive cells within atherosclerotic lesions (P=0.041). Our findings suggest that rosuvastatin reduces the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilisation and recruitment into vascular lesions.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  6. TRAF3IP2 mediates atherosclerotic plaque development and vulnerability in ApoE−/− mice

    Science.gov (United States)

    Prasad, Sakamuri Siva Sankara Vara; Higashi, Yusuke; Sukhanov, Sergiy; Siddesha, Jalahalli M; Delafontaine, Patrice; Siebenlist, Ulrich; Chandrasekar, Bysani

    2016-01-01

    Background and aims Atherosclerosis is a major cause of heart attack and stroke. Inflammation plays a critical role in the development of atherosclerosis. Since the cytoplasmic adaptor molecule TRAF3IP2 (TRAF3-Interacting Protein 2) plays a causal role in various autoimmune and inflammatory diseases, we hypothesized that TRAF3IP2 mediates atherosclerotic plaque development. Methods TRAF3IP2/ApoE double knockout (DKO) mice were generated by crossing TRAF3IP2−/− and ApoE−/− mice. ApoE−/− mice served as controls. Both DKO and control mice were fed a high-fat diet for 12 weeks. Plasma lipids were measured by ELISA, atherosclerosis by en face analysis of aorta and plaque cross-section measurements at the aortic valve region, plaque necrotic core area, collagen and smooth muscle cell content by histomorphometry, and aortic gene expression by RT-qPCR. Results The plasma lipoprotein profile was not altered by TRAF3IP2 gene deletion in ApoE−/− mice. While total aortic plaque area was decreased in DKO female, but not male mice, the plaque necrotic area was significantly decreased in DKO mice of both genders. Plaque collagen and smooth muscle cell contents were increased significantly in both female and male DKO mice compared to respective controls. Aortic expression of proinflammatory cytokine (Tumor necrosis factor α, TNFα), chemokine (Chemokine (C-X-C motif) Ligand 1, CXCL1) and adhesion molecule (Vascular cell adhesion molecule 1, VCAM1; and Intercellular adhesion molecule 1, ICAM1) gene expression were decreased in both male and female DKO mice. In addition, the male DKO mice showed a markedly reduced expression of extracellular matrix (ECM)-related genes, including TIMP1 (Tissue inhibitor of metalloproteinase 1), RECK (Reversion-Inducing- Cysteine-Rich Protein with Kazal Motifs) and ADAM17 (A Disintegrin And Metalloproteinase 17). Conclusions TRAF3IP2 plays a causal role in atherosclerotic plaque development and vulnerability, possibly by inducing the

  7. New treatment of iliac artery disease: focus on the Absolute Pro® Vascular Self-Expanding Stent System

    Directory of Open Access Journals (Sweden)

    Gates L

    2013-09-01

    Full Text Available Lindsay Gates, Jeffrey Indes Vascular and Endovascular Surgery, Yale University School of Medicine, New Haven, CT, USA Abstract: Management of iliac artery disease has evolved over the years, from a surgical-only approach to a primarily endovascular-only approach as the first line treatment option. This has been continuously improved upon with the advent of new devices and applied technologies. Most recently in particular, the literature has shown good, reliable outcomes with the use of self-expandable stents in iliac artery atherosclerotic lesions. Nevertheless, no device is without its limitations, and the Absolute Pro® Vascular Self-Expanding Stent System was designed with the intent of overcoming some of the shortcomings of other available stents while maintaining acceptable postprocedural outcomes. Based on preliminary industry-acquired data, it has achieved these goals and appears to be an emergent competitor for the treatment of both focal and complex iliac artery lesions. Keywords: Absolute-Pro®, iliac stent, self-expanding stents, atherosclerotic disease

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-30

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

  9. Angiogenesis Research to Improve Therapies for Vascular Leak Syndromes, Intra-abdominal Adhesions, and Arterial Injuries

    Science.gov (United States)

    2008-04-01

    for example, infantile haemangiomas6, peptic ulcers7, ocular neovascularization8, rheumatoid arthritis9 and atherosclerosis3,10,11. This led to a...Symptoms Diabetic retinopathy Loss of vision Rheumatoid arthritis2 Pain and immobility from destroyed cartilage Atherosclerotic plaques3 Chest pain, dyspnoea...2006) NSCLC, GIST, diabetic retinopathy, vascular occlusions, retinopathy of prematurity, colorectal, breast, ovarian, peritoneal, pancreatic

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  11. 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.

  12. Bone marrow endothelial progenitors in atherosclerotic plaque resolution

    Science.gov (United States)

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

    2013-01-01

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

  13. Increased activity of vascular adenosine deaminase in atherosclerosis and therapeutic potential of its inhibition.

    Science.gov (United States)

    Kutryb-Zajac, Barbara; Mateuszuk, Lukasz; Zukowska, Paulina; Jasztal, Agnieszka; Zabielska, Magdalena A; Toczek, Marta; Jablonska, Patrycja; Zakrzewska, Agnieszka; Sitek, Barbara; Rogowski, Jan; Lango, Romuald; Slominska, Ewa M; Chlopicki, Stefan; Smolenski, Ryszard T

    2016-11-01

    Extracellular nucleotides and adenosine that are formed or degraded by membrane-bound ecto-enzymes could affect atherosclerosis by regulating the inflammation and thrombosis. This study aimed to evaluate a relation between ecto-enzymes that convert extracellular adenosine triphosphate to adenine dinucleotide phosphate, adenosine monophosphate, adenosine, and inosine on the surface of the vessel wall with the severity or progression of experimental and clinical atherosclerosis. Furthermore, we tested whether the inhibition of adenosine deaminase will block the development of experimental atherosclerosis. Vascular activities of ecto-nucleoside triphosphate diphosphohydrolase 1, ecto-5'-nucleotidase, and ecto-adenosine deaminase (eADA) were measured in aortas of apolipoprotein E-/- low density lipoprotein receptor (ApoE-/-LDLR-/-) and wild-type mice as well as in human aortas. Plaques were analysed in the entire aorta, aortic root, and brachiocephalic artery by Oil-Red O and Orcein Martius Scarlet Blue staining and vascular accumulation of macrophages. The cellular location of ecto-enzymes was analysed by immunofluorescence. The effect of eADA inhibition on atherosclerosis progression was studied by a 2-month deoxycoformycin treatment of ApoE-/-LDLR-/- mice. The vascular eADA activity prominently increased in ApoE-/-LDLR-/- mice when compared with wild type already at the age of 1 month and progressed along atherosclerosis development, reaching a 10-fold difference at 10 months. The activity of eADA correlated with atherosclerotic changes in human aortas. High abundance of eADA in atherosclerotic vessels originated from activated endothelial cells and macrophages. There were no changes in ecto-nucleoside triphosphate diphosphohydrolase 1 activity, whereas ecto-5'-nucleotidase was moderately decreased in ApoE-/-LDLR-/- mice. Deoxycoformycin treatment attenuated plaque development in aortic root and brachiocephalic artery of ApoE-/-LDLR-/- mice, suppressed vascular

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

    International Nuclear Information System (INIS)

    Zhang Yongxue; Wu Zhijian; Cao Wei

    2000-01-01

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

  15. Electrical impedance of layered atherosclerotic plaques on human aortas

    NARCIS (Netherlands)

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

    1992-01-01

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

  16. Macrophage antioxidant protection within atherosclerotic plaques.

    Science.gov (United States)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  18. Increased metabolite levels of glycolysis and pentose phosphate pathway in rabbit atherosclerotic arteries and hypoxic macrophage.

    Directory of Open Access Journals (Sweden)

    Atsushi Yamashita

    Full Text Available AIMS: Inflammation and possibly hypoxia largely affect glucose utilization in atherosclerotic arteries, which could alter many metabolic systems. However, metabolic changes in atherosclerotic plaques remain unknown. The present study aims to identify changes in metabolic systems relative to glucose uptake and hypoxia in rabbit atherosclerotic arteries and cultured macrophages. METHODS: Macrophage-rich or smooth muscle cell (SMC-rich neointima was created by balloon injury in the iliac-femoral arteries of rabbits fed with a 0.5% cholesterol diet or a conventional diet. THP-1 macrophages stimulated with lipopolysaccharides (LPS and interferon-γ (INFγ were cultured under normoxic and hypoxic conditions. We evaluated comprehensive arterial and macrophage metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using (18F-fluorodeoxyglucose ((18F-FDG and pimonidazole, a marker of hypoxia. RESULTS: The levels of many metabolites increased in the iliac-femoral arteries with macrophage-rich neointima, compared with those that were not injured and those with SMC-rich neointima (glycolysis, 4 of 9; pentose phosphate pathway, 4 of 6; tricarboxylic acid cycle, 4 of 6; nucleotides, 10 of 20. The uptake of (18F-FDG in arterial walls measured by autoradiography positively correlated with macrophage- and pimonidazole-immunopositive areas (r = 0.76, and r = 0.59 respectively; n = 69 for both; p<0.0001. Pimonidazole immunoreactivity was closely localized with the nuclear translocation of hypoxia inducible factor-1α and hexokinase II expression in macrophage-rich neointima. The levels of glycolytic (8 of 8 and pentose phosphate pathway (4 of 6 metabolites increased in LPS and INFγ stimulated macrophages under hypoxic but not normoxic condition. Plasminogen activator inhibitor-1 protein levels in the supernatant were closely

  19. Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration.

    Science.gov (United States)

    Kesavan, R; Chandel, S; Upadhyay, S; Bendre, R; Ganugula, R; Potunuru, U R; Giri, H; Sahu, G; Kumar, P Uday; Reddy, G Bhanuprakash; Joksic, G; Bera, A K; Dixit, Madhulika

    2016-04-01

    Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-α induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-γ activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

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

    Science.gov (United States)

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

    2018-08-07

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  2. Association of dietary nitrate with atherosclerotic vascular disease mortality: a prospective cohort study of older adult women.

    Science.gov (United States)

    Blekkenhorst, Lauren C; Bondonno, Catherine P; Lewis, Joshua R; Devine, Amanda; Woodman, Richard J; Croft, Kevin D; Lim, Wai H; Wong, Germaine; Beilin, Lawrence J; Prince, Richard L; Hodgson, Jonathan M

    2017-07-01

    Background: Nitrate-rich vegetables lower blood pressure and improve endothelial function in humans. It is not known, however, whether increased consumption of nitrate-rich vegetables translates to a lower risk of atherosclerotic vascular disease (ASVD) mortality. Objective: The objective was to investigate the association of nitrate intake from vegetables with ASVD mortality. Design: A total of 1226 Australian women aged 70-85 y without prevalent ASVD and/or diabetes were recruited in 1998 and were studied for 15 y. We assessed demographic and ASVD risk factors at baseline (1998), and we used a validated food-frequency questionnaire to evaluate dietary intake. Nitrate intake from vegetables was calculated by use of a newly developed comprehensive database. The primary outcome was any death attributed to ASVD ascertained by using linked data that were provided via the Western Australian Data Linkage system. We used Cox proportional hazards modeling to examine the association between nitrate intake and ASVD mortality before and after adjustment for lifestyle and cardiovascular disease risk factors. Results: During a follow-up period of 15,947 person-years, 238 of 1226 (19.4%) women died of ASVD-related causes. The mean ± SD vegetable nitrate intake was 67.0 ± 29.2 mg/d. Each SD higher vegetable nitrate intake was associated with a lower risk of ASVD mortality in both unadjusted [HR: 0.80 (95% CI: 0.70, 0.92), P = 0.002] and multivariable-adjusted [HR: 0.79 (95% CI: 0.68, 0.93), P = 0.004] analyses. This relation was attenuated after further adjustment for diet quality [HR: 0.85 (95% CI: 0.72, 1.01), P = 0.072]. Higher vegetable nitrate intake (per SD) also was associated with a lower risk of all-cause mortality [multivariable-adjusted HR: 0.87 (95% CI: 0.78, 0.97), P = 0.011]. Conclusions: Nitrate intake from vegetables was inversely associated with ASVD mortality independent of lifestyle and cardiovascular disease risk factors in this population of older adult

  3. Atherosclerotic stenoses of renal arteries: Evaluation with CT

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  4. Exercise training protects against atherosclerotic risk factors through vascular NADPH oxidase, extracellular signal-regulated kinase 1/2 and stress-activated protein kinase/c-Jun N-terminal kinase downregulation in obese rats.

    Science.gov (United States)

    Touati, Sabeur; Montezano, Augusto C I; Meziri, Fayçal; Riva, Catherine; Touyz, Rhian M; Laurant, Pascal

    2015-02-01

    Exercise training reverses atherosclerotic risk factors associated with metabolic syndrome and obesity. The aim of the present study was to determine the molecular anti-inflammatory, anti-oxidative and anti-atherogenic effects in aorta from rats with high-fat diet-induced obesity. Male Sprague-Dawley rats were placed on a high-fat (HFD) or control (CD) diet for 12 weeks. The HFD rats were then divided into four groups: (i) sedentary HFD-fed rats (HFD-S); (ii) exercise trained (motor treadmill 5 days/week, 60 min/day, 12 weeks) HFD-fed rats (HFD-Ex); (iii) modified diet (HFD to CD) sedentary rats (HF/CD-S); and (iv) an exercise-trained modified diet group (HF/CD-Ex). Tissue levels of NADPH oxidase (activity and expression), NADPH oxidase (Nox) 1, Nox2, Nox4, p47(phox) , superoxide dismutase (SOD)-1, angiotensin AT1 and AT2 receptors, phosphorylated mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase (ERK) 1/2, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the aorta. Plasma cytokines (tumour necrosis factor (TNF)-α and interleukin (IL)-6) levels were also measured. Obesity was accompanied by increases in NADPH oxidase activity, p47(phox) translocation, Nox4 and VCAM-1 protein expression, MAPK (ERK1/2, SAPK/JNK) phosphorylation and plasma TNF-α and IL-6 levels. Exercise training and switching from the HFD to CD reversed almost all these molecular changes. In addition, training increased aortic SOD-1 protein expression and decreased ERK1/2 phosphorylation. These findings suggest that protective effects of exercise training on atherosclerotic risk factors induced by obesity are associated with downregulation of NADPH oxidase, ERK1/2 and SAPK/JNK activity and increased SOD-1 expression. © 2014 Wiley Publishing Asia Pty Ltd.

  5. Global gene expression profiling displays a network of dysregulated genes in non-atherosclerotic arterial tissue from patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Skov Vibe

    2012-02-01

    Full Text Available Abstract Background Generalized arterial alterations, such as endothelial dysfunction, medial matrix accumulations, and calcifications are associated with type 2 diabetes (T2D. These changes may render the vessel wall more susceptible to injury; however, the molecular characteristics of such diffuse pre-atherosclerotic changes in diabetes are only superficially known. Methods To identify the molecular alterations of the generalized arterial disease in T2D, DNA microarrays were applied to examine gene expression changes in normal-appearing, non-atherosclerotic arterial tissue from 10 diabetic and 11 age-matched non-diabetic men scheduled for a coronary by-pass operation. Gene expression changes were integrated with GO-Elite, GSEA, and Cytoscape to identify significant biological pathways and networks. Results Global pathway analysis revealed differential expression of gene-sets representing matrix metabolism, triglyceride synthesis, inflammation, insulin signaling, and apoptosis. The network analysis showed a significant cluster of dysregulated genes coding for both intra- and extra-cellular proteins associated with vascular cell functions together with genes related to insulin signaling and matrix remodeling. Conclusions Our results identify pathways and networks involved in the diffuse vasculopathy present in non-atherosclerotic arterial tissue in patients with T2D and confirmed previously observed mRNA-alterations. These abnormalities may play a role for the arterial response to injury and putatively for the accelerated atherogenesis among patients with diabetes.

  6. Are calcifying matrix vesicles in atherosclerotic lesions of cellular origin?

    Science.gov (United States)

    Bobryshev, Yuri V; Killingsworth, Murray C; Huynh, Thuan G; Lord, Reginald S A; Grabs, Anthony J; Valenzuela, Stella M

    2007-03-01

    Over recent years, the role of matrix vesicles in the initial stages of arterial calcification has been recognized. Matrix calcifying vesicles have been isolated from atherosclerotic arteries and the biochemical composition of calcified vesicles has been studied. No studies have yet been carried out to examine the fine structure of matrix vesicles in order to visualize the features of the consequent stages of their calcification in arteries. In the present work, a high resolution ultrastructural analysis has been employed and the study revealed that matrix vesicles in human atherosclerotic lesions are heterogeneous with two main types which we classified. Type I calcified vesicles were presented by vesicles surrounded by two electron-dense layers and these vesicles were found to be resistant to the calcification process in atherosclerotic lesions in situ. Type II matrix vesicles were presented by vesicles surrounded by several electron-dense layers and these vesicles were found to represent calcifying vesicles in atherosclerotic lesions. To test the hypothesis that calcification of matrix vesicles surrounded by multilayer sheets may occur simply as a physicochemical process, independently from the cell regulation, we produced multilamellar liposomes and induced their calcification in vitro in a manner similar to that occurring in matrix vesicles in atherosclerotic lesions in situ.

  7. 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

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

  8. Patients with atherosclerotic vascular disease: how low should plasma homocyst(e)ine levels go?

    Science.gov (United States)

    Spence, J D

    2001-01-01

    Plasma homocyst(e)ine level is a strong independent risk factor for vascular disease. The spelling of homocyst(e)ine reflects that what is measured, and what constitutes the risk factor; it includes homocysteine, homocystine (the dimer of homocysteine) and mixed cysteine-homocysteine disulfide. Homocyst(e)ine levels above 10.2 micro mol/L are associated with a doubling of coronary risk, and levels above 20 micro mol/L are associated with a 9.9-fold increase in risk compared with levels below 9 micro mol/L. The mechanisms by which homocyst(e)ine promotes vascular disease include increased thrombosis, consumption of nitric oxide, endothelial injury, and reduced thrombolysis. Homocyst(e)ine is an independent predictor of carotid atherosclerosis. Vitamin therapy with folate, pyridoxine (vitamin B(6)), and cyanocobalamin (vitamin B(12)) reduces blood levels of homocyst(e)ine, improves endothelial function, reduces levels of fibrinogen and lipoprotein(a), improves thrombolysis, and in uncontrolled clinical observation, leads to regression of carotid plaque. These lines of evidence support a causal relationship between homocyst(e)ine and atherosclerosis, and suggest that in patients with vascular disease, an appropriate target level for therapy may be below 9 or 10 micro mol/L. Randomized controlled studies are under way to determine whether vitamin therapy is effective in secondary prevention of myocardial infarction and stroke.

  9. The pathology and pathophysiology of vascular dementia.

    Science.gov (United States)

    Kalaria, Raj N

    2017-12-19

    Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

    Science.gov (United States)

    Kovanen, Petri T; Bot, Ilze

    2017-12-05

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

  11. Decreased distensibility of a passive vascular bed in diabetes mellitus

    DEFF Research Database (Denmark)

    Faris, I; Agerskov, K; Henrikson, O

    1982-01-01

    exercise and (b) in a vascular bed locally paralysed by the injection of papaverine. Five normal subjects, six patients with long-standing Type 1 diabetes and six non-diabetic patients with severe atherosclerosis affecting the legs were studied. Blood flow was measured in the anterior tibial muscle......This study was undertaken to determine whether the distensibility of a passive vascular bed is reduced in Type 1 (insulin-dependent) diabetic patients with microangiopathy. The change in blood flow induced by 45 degrees head-up tilting was studied in two systems: (a) following maximal ischaemic...... by the isotope washout technique. The median increase in blood flow produced by tilting was greater in normal subjects than in diabetic subjects in both the locally-relaxed bed (58% and 14% respectively) and after maximal ischaemic exercise (45% and 4% respectively). In the atherosclerotic subjects, the increase...

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

    Directory of Open Access Journals (Sweden)

    Ricardo A Garcia

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

  13. 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

  14. PET/CT for atherosclerotic plaque imaging

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  15. Emerging Technology Update Intravascular Photoacoustic Imaging of Vulnerable Atherosclerotic Plaque.

    Science.gov (United States)

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

    2016-10-01

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

  16. Towards the therapeutic use of vascular smooth muscle progenitor cells.

    Science.gov (United States)

    Merkulova-Rainon, Tatyana; Broquères-You, Dong; Kubis, Nathalie; Silvestre, Jean-Sébastien; Lévy, Bernard I

    2012-07-15

    Recent advances in the development of alternative proangiogenic and revascularization processes, including recombinant protein delivery, gene therapy, and cell therapy, hold the promise of greater efficacy in the management of cardiovascular disease in the coming years. In particular, vascular progenitor cell-based strategies have emerged as an efficient treatment approach to promote vessel formation and repair and to improve tissue perfusion. During the past decade, considerable progress has been achieved in understanding therapeutic properties of endothelial progenitor cells, while the therapeutic potential of vascular smooth muscle progenitor cells (SMPC) has only recently been explored; the number of the circulating SMPC being correlated with cardiovascular health. Several endogenous SMPC populations with varying phenotypes have been identified and characterized in the peripheral blood, bone marrow, and vascular wall. While the phenotypic entity of vascular SMPC is not fully defined and remains an evolving area of research, SMPC are increasingly recognized to play a special role in cardiovascular biology. In this review, we describe the current approaches used to define vascular SMPC. We further summarize the data on phenotype and functional properties of SMPC from various sources in adults. Finally, we discuss the role of SMPC in cardiovascular disease, including the contribution of SMPC to intimal proliferation, angiogenesis, and atherosclerotic plaque instability as well as the benefits resulting from the therapeutic use of SMPC.

  17. Bone marrow endothelial progenitors augment atherosclerotic plaque regression in a mouse model of plasma lipid lowering

    Science.gov (United States)

    Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Iida, Ryuji; Wang, Qilong; Zou, Ming-Hui; Barlic-Dicen, Jana

    2012-01-01

    The major event initiating atherosclerosis is hypercholesterolemia-induced disruption of vascular endothelium integrity. In settings of endothelial damage, endothelial progenitor cells (EPCs) are mobilized from bone marrow into circulation and home to sites of vascular injury where they aid endothelial regeneration. Given the beneficial effects of EPCs in vascular repair, we hypothesized that these cells play a pivotal role in atherosclerosis regression. We tested our hypothesis in the atherosclerosis-prone mouse model in which hypercholesterolemia, one of the main factors affecting EPC homeostasis, is reversible (Reversa mice). In these mice normalization of plasma lipids decreased atherosclerotic burden; however, plaque regression was incomplete. To explore whether endothelial progenitors contribute to atherosclerosis regression, bone marrow EPCs from a transgenic strain expressing green fluorescent protein under the control of endothelial cell-specific Tie2 promoter (Tie2-GFP+) were isolated. These cells were then adoptively transferred into atheroregressing Reversa recipients where they augmented plaque regression induced by reversal of hypercholesterolemia. Advanced plaque regression correlated with engraftment of Tie2-GFP+ EPCs into endothelium and resulted in an increase in atheroprotective nitric oxide and improved vascular relaxation. Similarly augmented plaque regression was also detected in regressing Reversa mice treated with the stem cell mobilizer AMD3100 which also mobilizes EPCs to peripheral blood. We conclude that correction of hypercholesterolemia in Reversa mice leads to partial plaque regression that can be augmented by AMD3100 treatment or by adoptive transfer of EPCs. This suggests that direct cell therapy or indirect progenitor cell mobilization therapy may be used in combination with statins to treat atherosclerosis. PMID:23081735

  18. Effect of Low Level Ionizing Radiation on Endothelial Progenitor Cells in Atherosclerotic Patients with Lower Limb Ischemia

    International Nuclear Information System (INIS)

    Taha, E.F.S.

    2013-01-01

    Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality throughout the developed world (Williamson et al., 2012). Coronary artery disease (CAD) or atherosclerotic heart disease is a chronic life-threatening disease, which characterized by reducing blood supply to the heart as a result of the accumulation of atheromatous plaques within the walls of the arteries supplying the myocardium. Progressive atherosclerosis in the coronary arteries may lead to intimal thickening and eventual artery occlusion. Coronary artery occlusion can cause acute myocardial ischemia as a result of reduced oxygen supply or increased oxygen demand (Luthje and Andreas, 2008). Convincing evidence indicates that atherosclerosis is associated with endothelial dysfunction at the early stage of the disease process (Chiang et al., 2012). The endothelium is a dynamic cell layer that represents a physiological barrier between circulating blood and the surrounding tissues. Impaired endothelial function is a critical event in the initiation of atherosclerotic plaque development and thus may lead to vasoconstriction, vascular smooth muscle proliferation, hypercoagulability, thrombosis, and eventually, adverse cardiovascular events (Berger and Lavie, 2011). Asahara et al., (1997) described endothelial progenitor cells (EPC) in human peripheral blood. EPC are immature endothelial circulating cells mobilized from the bone marrow. These cells are involved in Introduction and aim of the work repairing the damaged endothelium and in facilitating neovascularization after ischemia (Rouhl et al., 2008). The role of EPC in health and disease is not understood completely. Most studies of healthy subjects and patients with coronary artery disease (CAD) report that the number and function of circulating EPC decrease with age and with the presence of classical vascular risk factors (Fadini et al., 2007). Recent studies suggested that EPCs play an important role in the risk of vascular

  19. IAP survivin regulates atherosclerotic macrophage survival

    NARCIS (Netherlands)

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

    2007-01-01

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

  20. Emerging applications of nanotechnology for the diagnosis and management of vulnerable atherosclerotic plaques

    Science.gov (United States)

    Yu, Shann S.; Ortega, Ryan A.; Reagan, Brendan W.; McPherson, John A.; Sung, Hak-Joon; Giorgio, Todd D.

    2017-01-01

    An estimated 16 million people in the United States have coronary artery disease (CAD), and approximately 325,000 people die annually from cardiac arrest. About two-thirds of unexpected cardiac deaths occur without prior recognition of cardiac disease. A vast majority of these deaths are attributable to the rupture of ‘Vulnerable atherosclerotic plaques’. Clinically, plaque vulnerability is typically assessed through imaging techniques, and ruptured plaques leading to acute myocardial infarction are treated through angioplasty or stenting. Despite significant advances, it is clear that current imaging methods are insufficiently capable for elucidating plaque composition—which is a key determinant of vulnerability. Further, the exciting improvement in the treatment of CAD afforded by stenting procedures has been buffered by significant undesirable host-implant effects, including restenosis and late thrombosis. Nanotechnology has led to some potential solutions to these problems by yielding constructs that interface with plaque cellular components at an unprecedented size scale. By leveraging the innate ability of macrophages to phagocytose nanoparticles, contrast agents can now be targeted to plaque inflammatory activity. Improvements in nano-patterning procedures have now led to increased ability to regenerate tissue isotropy directly on stents, enabling gradual regeneration of normal, physiologic vascular structures. Advancements in immunoassay technologies promise lower costs for biomarker measurements, and in the near future, may enable the addition of routine blood testing to the clinician’s toolbox—decreasing the costs of atherosclerosis-related medical care. These are merely three examples among many stories of how nanotechnology continues to promise advances in the diagnosis and treatment of vulnerable atherosclerotic plaques. PMID:21834059

  1. 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.)

  2. How to manage hypertension with atherosclerotic renal artery stenosis?

    Science.gov (United States)

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

    2017-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Ya Liu

    2013-09-01

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

  4. Progranulin expression in advanced human atherosclerotic plaque.

    Science.gov (United States)

    Kojima, Yoji; Ono, Koh; Inoue, Katsumi; Takagi, Yasushi; Kikuta, Ken-ichiro; Nishimura, Masaki; Yoshida, Yoshinori; Nakashima, Yasuhiro; Matsumae, Hironobu; Furukawa, Yutaka; Mikuni, Nobuhiro; Nobuyoshi, Masakiyo; Kimura, Takeshi; Kita, Toru; Tanaka, Makoto

    2009-09-01

    Progranulin (PGRN) is a unique growth factor that plays an important role in cutaneous wound healing. It has an anti-inflammatory effect and promotes cell proliferation. However, when it is degraded to granulin peptides (GRNs) by neutrophil proteases, a pro-inflammatory reaction occurs. Since injury, inflammation and repair are common features in the progression of atherosclerosis, it is conceivable that PGRN plays a role in atherogenesis. Immunohistochemical analysis of human carotid endoatherectomy specimens indicated that vascular smooth muscle cells (vSMCs) in the intima expressed PGRN. Some macrophages in the plaque also expressed PGRN. We assessed the effect of PGRN on a human monocytic leukemia cell line (THP-1) and human aortic smooth muscle cells (HASMCs). PGRN alone had no effect on HASMC or THP-1 proliferation or migration. However, when THP-1 cells were stimulated with MCP-1, the number of migrated cells decreased in a PGRN-dose-dependent manner. TNF-alpha-induced HASMC migration was enhanced only at 10nM of PGRN. Interleukin-8 (IL-8) secretion from HASMCs was reduced by forced expression of PGRN and increased by RNAi-mediated knockdown of PGRN. While exogenous treatment with recombinant PGRN decreased IL-8 secretion, degraded recombinant GRNs increased IL-8 secretion from HASMCs. The expression of PGRN mainly reduces inflammation and its degradation into GRNs enhances inflammation in atherosclerotic plaque and may contribute to the progression of atherosclerosis.

  5. Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions

    Science.gov (United States)

    Almer, Gunter; Saba-Lepek, Matthias; Haj-Yahya, Samih; Rohde, Eva; Strunk, Dirk; Fröhlich, Eleonore; Prassl, Ruth; Mangge, Harald

    2011-01-01

    Background: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions. Methods: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy. Results: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice. Conclusion: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions. PMID:22022204

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

    Science.gov (United States)

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

    2018-03-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. The LOX-1 Scavenger Receptor and Its Implications in the Treatment of Vascular Disease

    Directory of Open Access Journals (Sweden)

    M. W Twigg

    2012-01-01

    Full Text Available Cardiovascular disease is the leading cause of death. The disease is due to atherosclerosis which is characterized by lipid and fat accumulation in arterial blood vessel walls. A key causative event is the accumulation of oxidised low density lipoprotein particles within vascular cells, and this is mediated by scavenger receptors. One such molecule is the LOX-1 scavenger receptor that is expressed on endothelial, vascular smooth muscle, and lymphoid cells including macrophages. LOX-1 interaction with OxLDL particles stimulates atherosclerosis. LOX-1 mediates OxLDL endocytosis via a clathrin-independent internalization pathway. Transgenic animal model studies show that LOX-1 plays a significant role in atherosclerotic plaque initiation and progression. Administration of LOX-1 antibodies in cellular and animal models suggest that such intervention inhibits atherosclerosis. Antiatherogenic strategies that target LOX-1 function using gene therapy or small molecule inhibitors would be new ways to address the increasing incidence of vascular disease in many countries.

  9. Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease

    DEFF Research Database (Denmark)

    Hansen, Peter Riis

    2018-01-01

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

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

    International Nuclear Information System (INIS)

    Cao Wei; Zhang Yongxue; An Rui

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Christopher A Drummond

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

  12. Efecto morfológico y funcional vascular de los andrógenos endógenos en un modelo experimental en conejos ateroscleróticos Vascular morphologic and functional effect of endogenous androgens in an experimental atherosclerotic rabbits' model

    Directory of Open Access Journals (Sweden)

    Darío Echeverri

    2007-12-01

    plaque formation. Results: animals that had a normal diet (n=20 had total cholesterol of 51.1 ± 8.5 mg/dl and those with atherogenic diet, of 429.2 ± 262.0 mg/dl (p< 0.001. Testosterone levels in the non- castrated group were 2.1 ± 0.3 ng/mL and in the castrated were 0.8 ± 0.4 ng/mL (p= 0.024. In non-castrated rabbits the effect of hypercholesteremia (366 ± 226.1 mg/dL inducing atherosclerotic plaque and functional vascular alteration was mild. On the other hand, atherogenic diet in castrated rabbits induced an increment in total cholesterol from 387.6 ± 292.7 mg/dL (p <0.001 and severe morphological changes such as plaque area 2.6 ± 2.3mm² (p <0.001, vessel plaque/area 0.25 ± 0.1 (p <0.001 and area index of plaque/area of the media 0.4 ± 0.3 (p <0.001. Endothelium independent relaxation percentage was 85.5 ± 14.3% (p = NS and endothelium dependent relaxation was 38.5 ± 20.1% (p = 0.03. Conclusion: this study realized in rabbits demonstrates that endogenous testosterone might have a preventive effect on atherosclerosis and favor endothelium dependent vascular relaxation in the presence of severe hypercholesterolemia.

  13. Implication of molecular vascular smooth muscle cell heterogeneity among arterial beds in arterial calcification.

    Directory of Open Access Journals (Sweden)

    Olivier Espitia

    Full Text Available Vascular calcification is a strong and independent predictive factor for cardiovascular complications and mortality. Our previous work identified important discrepancies in plaque composition and calcification types between carotid and femoral arteries. The objective of this study is to further characterize and understand the heterogeneity in vascular calcification among vascular beds, and to identify molecular mechanisms underlying this process. We established ECLAGEN biocollection that encompasses human atherosclerotic lesions and healthy arteries from different locations (abdominal, thoracic aorta, carotid, femoral, and infrapopliteal arteries for histological, cell isolation, and transcriptomic analysis. Our results show that lesion composition differs between these locations. Femoral arteries are the most calcified arteries overall. They develop denser calcifications (sheet-like, nodule, and are highly susceptible to osteoid metaplasia. These discrepancies may derive from intrinsic differences between SMCs originating from these locations, as microarray analysis showed specific transcriptomic profiles between primary SMCs isolated from each arterial bed. These molecular differences translated into functional disparities. SMC from femoral arteries showed the highest propensity to mineralize due to an increase in basal TGFβ signaling. Our results suggest that biological heterogeneity of resident vascular cells between arterial beds, reflected by our transcriptomic analysis, is critical in understanding plaque biology and calcification, and may have strong implications in vascular therapeutic approaches.

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

    Science.gov (United States)

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

    1998-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xie S

    2009-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  18. PET/CT and vascular disease: Current concepts

    Energy Technology Data Exchange (ETDEWEB)

    Cavalcanti Filho, Jose Leite Gondim; Souza Leao Lima, Ronaldo de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Souza Machado Neto, Luiz de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Kayat Bittencourt, Leonardo, E-mail: lkayat@terra.com.br [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Cortes Domingues, Romeu [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Fonseca, Lea Mirian Barbosa da [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil)

    2011-10-15

    Since its introduction in 2001, positron emission tomography associated to computed tomography (PET/CT) has been established as a standard tool in cancer evaluation. Being a multimodality imaging method, it combines in a single session the sensitivity granted by PET for detection of molecular targets within the picomolar range, with an underlying submilimetric resolution inherent to CT, that can precisely localize the PET findings. In this last decade, there have been new insights regarding the pathophysiology of atherosclerosis, particularly about plaque rupture and vascular remodeling. This has increased the interest for research on PET/CT in vascular diseases as a potential new diagnostic tool, since some PET molecular targets could identify diseases before the manifestation of gross anatomic features. In this review, we will describe the current applications of PET/CT in vascular diseases, emphasizing its usefulness in the settings of vasculitis, aneurysms, vascular graft infection, aortic dissection, and atherosclerosis/plaque vulnerability. Although not being properly peripheral vascular conditions, ischemic cardiovascular disease and cerebrovascular disease will be briefly addressed as well, due to their widespread prevalence and importance.

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

    Science.gov (United States)

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

    2017-04-01

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

  20. Contemporary medical therapies of atherosclerotic carotid artery disease.

    Science.gov (United States)

    Cheng, Suk F; Brown, Martin M

    2017-03-01

    Contemporary medical therapy consists of identification and treatment of all patient-modifiable vascular risk factors. Specific atherosclerotic disease therapies are designed to reduce the risk of thrombosis, and the disease progression in order to reduce the risk of future cardiovascular events. Contemporary medical management emphasizes the need to support the patient in achieving lifestyle modifications and to adjust medication to achieve individualized target values for specific quantifiable risk factors. Antiplatelet therapy in the form of aspirin or clopidogrel is routinely used for the prevention of ischemic stroke in patients who have had a transient ischemic attack or stroke. There is evidence from a recent trial that the use of combination antiplatelet therapy with aspirin and clopidogrel started within 24 hours of minor stroke or transient ischemic attack reduces the risk of recurrent stroke compared to the use of aspirin alone, and therefore we use aspirin plus clopidogrel in recently symptomatic patients with carotid stenosis pending carotid revascularization. Anticoagulation with heparins or vitamin K antagonist is not recommended except in patients at risk for cardio-embolic events. Lowering blood pressure to target levels has been shown to slow down the progression of carotid artery stenosis and reduces the intima-media thickness of the carotid plaque, while lowering lipid levels with statins has become an essential element in the medical therapy of carotid artery stenosis. Diabetes management should be optimized. Lifestyle choices, including tobacco smoking, physical inactivity, unhealthy diet, obesity, and excessive alcohol intake, are all important modifiable vascular risk factors. The combination of dietary modification, physical exercise, and use of aspirin, a statin, and an antihypertensive agent can be expected to give a cumulative relative stroke risk reduction of 80%. The evidence suggests that intensive medical therapy is so effective that

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

    Science.gov (United States)

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

    2018-01-01

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

  2. In-depth evaluation of commercially available human vascular smooth muscle cells phenotype: Implications for vascular tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Timraz, Sara B.H., E-mail: sara.timraz@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Farhat, Ilyas A.H., E-mail: ilyas.farhat@outlook.com [Department of Applied Mathematics and Sciences, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Alhussein, Ghada, E-mail: ghada.alhussein@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Christoforou, Nicolas, E-mail: nicolas.christoforou@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates); Department of Biomedical Engineering, Duke University, Durham, NC 27708 (United States); Teo, Jeremy C.M., E-mail: jeremy.teo@kustar.ac.ae [Department of Biomedical Engineering, Khalifa University, PO Box 127788, Abu Dhabi (United Arab Emirates)

    2016-05-01

    In vitro research on vascular tissue engineering has extensively used isolated primary human or animal smooth muscle cells (SMC). Research programs that lack such facilities tend towards commercially available primary cells sources. Here, we aim to evaluate the capacity of commercially available human SMC to maintain their contractile phenotype, and determine if dedifferentiation towards the synthetic phenotype occurs in response to conventional cell culture and passaging without any external biochemical or mechanical stimuli. Lower passage SMC adopted a contractile phenotype marked by a relatively slower proliferation rate, higher expression of proteins of the contractile apparatus and smoothelin, elongated morphology, and reduced deposition of collagen types I and III. As the passage number increased, migratory capacity was enhanced, average cell speed, total distance and net distance travelled increased up to passage 8. Through the various assays, corroborative evidence pinpoints SMC at passage 7 as the transition point between the contractile and synthetic phenotypes, while passage 8 distinctly and consistently exhibited characteristics of synthetic phenotype. This knowledge is particularly useful in selecting SMC of appropriate passage number for the target vascular tissue engineering application, for example, a homeostatic vascular graft for blood vessel replacement versus recreating atherosclerotic blood vessel model in vitro. - Highlights: • Ability of human smooth muscle cells to alter phenotype in culture is evaluated. • Examined the effect of passaging human smooth muscle cells on phenotype. • Phenotype is assessed based on morphology, proliferation, markers, and migration. • Multi-resolution assessment methodology, single-cell and cell-population. • Lower and higher passages than P7 adopted a contractile and synthetic phenotype respectively.

  3. In-depth evaluation of commercially available human vascular smooth muscle cells phenotype: Implications for vascular tissue engineering

    International Nuclear Information System (INIS)

    Timraz, Sara B.H.; Farhat, Ilyas A.H.; Alhussein, Ghada; Christoforou, Nicolas; Teo, Jeremy C.M.

    2016-01-01

    In vitro research on vascular tissue engineering has extensively used isolated primary human or animal smooth muscle cells (SMC). Research programs that lack such facilities tend towards commercially available primary cells sources. Here, we aim to evaluate the capacity of commercially available human SMC to maintain their contractile phenotype, and determine if dedifferentiation towards the synthetic phenotype occurs in response to conventional cell culture and passaging without any external biochemical or mechanical stimuli. Lower passage SMC adopted a contractile phenotype marked by a relatively slower proliferation rate, higher expression of proteins of the contractile apparatus and smoothelin, elongated morphology, and reduced deposition of collagen types I and III. As the passage number increased, migratory capacity was enhanced, average cell speed, total distance and net distance travelled increased up to passage 8. Through the various assays, corroborative evidence pinpoints SMC at passage 7 as the transition point between the contractile and synthetic phenotypes, while passage 8 distinctly and consistently exhibited characteristics of synthetic phenotype. This knowledge is particularly useful in selecting SMC of appropriate passage number for the target vascular tissue engineering application, for example, a homeostatic vascular graft for blood vessel replacement versus recreating atherosclerotic blood vessel model in vitro. - Highlights: • Ability of human smooth muscle cells to alter phenotype in culture is evaluated. • Examined the effect of passaging human smooth muscle cells on phenotype. • Phenotype is assessed based on morphology, proliferation, markers, and migration. • Multi-resolution assessment methodology, single-cell and cell-population. • Lower and higher passages than P7 adopted a contractile and synthetic phenotype respectively.

  4. In vivo determination of arterial collagen synthesis in atherosclerotic rabbits

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  5. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  7. Sildenafil (Viagra® Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

    Directory of Open Access Journals (Sweden)

    Marcos A.S. Leal

    2017-12-01

    Full Text Available Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/- mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2, thromboxane A2 (TXA2 and endothelin-1 (ET-1 to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE in aortic rings were evaluated before and after incubation with Cox-1 (SC-560 or Cox-2 (NS-398 inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p<0.01, which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p<0.01, which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1. Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

  8. Initiation and Propagation of Vascular Calcification Is Regulated by a Concert of Platelet- and Smooth Muscle Cell-Derived Extracellular Vesicles

    Directory of Open Access Journals (Sweden)

    Leon J. Schurgers

    2018-04-01

    Full Text Available The ageing population continues to suffer from its primary killer, cardiovascular disease (CVD. Despite recent advances in interventional medicinal and surgical therapies towards the end of the 20th century, the epidemic of cardiovascular disease has not been halted. Yet, rather than receding globally, the burden of CVD has risen to become a top cause of morbidity and mortality worldwide. Most CVD arises from thrombotic rupture of an atherosclerotic plaque, the pathologic thickening of coronary and carotid artery segments and subsequent distal ischemia in heart or brain. In fact, one-fifth of deaths are directly attributable to thrombotic rupture of a vulnerable plaque. Atherosclerotic lesion formation is caused by a concert of interactions between circulating leukocytes and platelets, interacting with the endothelial barrier, signalling into the arterial wall by the release of cytokines and extracellular vesicles (EVs. Both platelet- and cell-derived EVs represent a novel mechanism of cellular communication, particularly by the transport and transfer of cargo and by reprogramming of the recipient cell. These interactions result in phenotypic switching of vascular smooth muscle cells (VSMCs causing migration and proliferation, and subsequent secretion of EVs. Loss of VSMCs attracts perivascular Mesenchymal Stem Cells (MSCs from the adventitia, which are a source of VSMCs and contribute to repair after vascular injury. However, continuous stress stimuli eventually switch phenotype of cells into osteochondrogenic VSMCs facilitating vascular calcification. Although Virchow’s triad is over 100 years old, it is a reality that is accurate today. It can be briefly summarised as changes in the composition of blood (platelet EVs, alterations in the vessel wall (VSMC phenotypic switching, MSC infiltration and EV release and disruption of blood flow (atherothrombosis. In this paper, we review the latest relevant advances in the identification of

  9. Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan

    DEFF Research Database (Denmark)

    Jensen, Tonny Joran

    1997-01-01

    that albuminuria is a marker of widespread vascular dysfunction. Increased transport of macromolecules across the vascular wall, elevated plasma levels of von Willebrand factor, and impaired fibrinolytic capacity have been demonstrated in albuminuric patients. The cause of this vascular vulnerability...... problems. What are the mechanisms of action of glycosaminoglycans at the molecular biology level, and how can we select compounds without anticoagulant activity suitable for long-term use in the prevention and treatment of late diabetic complications?...

  10. The contemporary management of intracranial atherosclerotic disease.

    Science.gov (United States)

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

    2016-06-01

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

  11. Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

    Science.gov (United States)

    Yahagi, Kazuyuki; Kolodgie, Frank D; Lutter, Christoph; Mori, Hiroyoshi; Romero, Maria E; Finn, Aloke V; Virmani, Renu

    2017-02-01

    The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification. © 2016 American Heart Association, Inc.

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

    Science.gov (United States)

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

    2015-12-01

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

  13. Ghrelin attenuates vascular calcification in diabetic patients with amputation.

    Science.gov (United States)

    Xu, Suining; Ye, Fei; Li, Lihua; Yan, Jinchuan; Bao, Zhengyang; Sun, Zhen; Xu, Liangjie; Zhu, Jie; Wang, Zhongqun

    2017-07-01

    Vascular calcification is established to be a critical factor in diabetes mellitus, which causes cardiovascular and amputation complication of diabetic patients. OPG/RANKL/RANK axis serves as a regulatory role in vascular calcification. Ghrelin, an endogenous ligand of growth hormone secretagogue receptor (GHSR), has been reported to exhibit potent cardiovascular protective effects. However, the role of ghrelin in the regulation of diabetic vascular calcification is still elusive. Here, we reported the role of ghrelin and its relationship with OPG/RANKL/RANK system in patients with diabetic foot amputation. In vivo and in vitro investigations were performed. Sixty type 2 diabetic patients with foot amputation were enrolled in vivo investigation, and they were divided into three groups through Doppler ultrasound: mild stenosis group (n=20), moderate stenosis group (n=20), and severe stenosis/occlusion group (n=20). Morphological analysis results showed diffused calcium depositions in the anterior tibial artery of diabetic amputees. Compared with the mild and moderate stenosis group, the severe stenosis/occlusion group had more spotty calcium depositions in atherosclerotic plaques. Western blot analysis indicated the expressions of osteoprotegerin (OPG) and ghrelin were downregulated, while the expression of receptor activator of nuclear factor kappa B ligand (RANKL) was upregulated with the vascular stenosis aggravation. Pearson correlation analysis revealed a negative correlation between calcium content and ghrelin levels (r=-0.58, Pghrelin levels and sRANKL levels (r=-0.57, Pghrelin levels (r=0.63, PGhrelin blunted calcification in a dose-dependent manner. In addition, ghrelin upregulated OPG expression and downregulated RANKL expression in VSMC calcification when anti-OPG antibody and RANKL were performed. Collectively, we therefore conclude serum ghrelin level may be a predictor of diabetic vascular calcification. The possible mechanism may be related with OPG

  14. {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.)

  15. Widespread osteonecrosis of the foot in systemic lupus erythematosus: Radiographic and gross pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Resnick, D; Pineda, C; Trudell, D

    1985-01-01

    A patient with systemic lupus erythematosus required an amputation of the foot related to the presence of vascular disease and infection. Radiographs obtained prior to amputation revealed osteonecrosis in virtually every bone of the foot. Radiographic-pathologic correlation documented this widespread osseous involvement. Although ischemic necrosis of bone is a well-known feature of systemic lupus erythematosus, its localization in the small bones of the foot is rare.

  16. Widespread osteonecrosis of the foot in systemic lupus erythematosus: Radiographic and gross pathologic correlation

    International Nuclear Information System (INIS)

    Resnick, D.; Pineda, C.; Trudell, D.; California Univ., San Diego, La Jolla

    1985-01-01

    A patient with systemic lupus erythematosus required an amputation of the foot related to the presence of vascular disease and infection. Radiographs obtained prior to amputation revealed osteonecrosis in virtually every bone of the foot. Radiographic-pathologic correlation documented this widespread osseous involvement. Although ischemic necrosis of bone is a well-known feature of systemic lupus erythematosus, its localization in the small bones of the foot is rare. (orig.)

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

    African Journals Online (AJOL)

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

  18. Palmitic Acid Induces Osteoblastic Differentiation in Vascular Smooth Muscle Cells through ACSL3 and NF-κB, Novel Targets of Eicosapentaenoic Acid

    Science.gov (United States)

    Kageyama, Aiko; Matsui, Hiroki; Ohta, Masahiko; Sambuichi, Keisuke; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Yokoyama, Tomoyuki; Kurabayashi, Masahiko

    2013-01-01

    Free fatty acids (FFAs), elevated in metabolic syndrome and diabetes, play a crucial role in the development of atherosclerotic cardiovascular disease, and eicosapentaenoic acid (EPA) counteracts many aspects of FFA-induced vascular pathology. Although vascular calcification is invariably associated with atherosclerosis, the mechanisms involved are not completely elucidated. In this study, we tested the hypothesis that EPA prevents the osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC) induced by palmitic acid (PA), the most abundant long-chain saturated fatty acid in plasma. PA increased and EPA abolished the expression of the genes for bone-related proteins, including bone morphogenetic protein (BMP)-2, Msx2 and osteopontin in human aortic smooth muscle cells (HASMC). Among the long-chain acyl-CoA synthetase (ACSL) subfamily, ACSL3 expression was predominant in HASMC, and PA robustly increased and EPA efficiently inhibited ACSL3 expression. Importantly, PA-induced osteoblastic differentiation was mediated, at least in part, by ACSL3 activation because acyl-CoA synthetase (ACS) inhibitor or siRNA targeted to ACSL3 completely prevented the PA induction of both BMP-2 and Msx2. Conversely, adenovirus-mediated ACSL3 overexpression enhanced PA-induced BMP-2 and Msx2 expression. In addition, EPA, ACSL3 siRNA and ACS inhibitor attenuated calcium deposition and caspase activation induced by PA. Notably, PA induced activation of NF-κB, and NF-κB inhibitor prevented PA-induction of osteoblastic gene expression and calcium deposition. Immunohistochemistry revealed the prominent expression of ACSL3 in VSMC and macrophages in human non-calcifying and calcifying atherosclerotic plaques from the carotid arteries. These results identify ACSL3 and NF-κB as mediators of PA-induced osteoblastic differentiation and calcium deposition in VSMC and suggest that EPA prevents vascular calcification by inhibiting such a new molecular pathway elicited

  19. IGF-1 Has Plaque-Stabilizing Effects in Atherosclerosis by Altering Vascular Smooth Muscle Cell Phenotype

    Science.gov (United States)

    von der Thüsen, Jan H.; Borensztajn, Keren S.; Moimas, Silvia; van Heiningen, Sandra; Teeling, Peter; van Berkel, Theo J.C.; Biessen, Erik A.L.

    2011-01-01

    Insulin-like growth factor-1 (IGF-1) signaling is important for the maintenance of plaque stability in atherosclerosis due to its effects on vascular smooth muscle cell (vSMC) phenotype. To investigate this hypothesis, we studied the effects of the highly inflammatory milieu of the atherosclerotic plaque on IGF-1 signaling and stability-related phenotypic parameters of murine vSMCs in vitro, and the effects of IGF-1 supplementation on plaque phenotype in an atherosclerotic mouse model. M1-polarized, macrophage-conditioned medium inhibited IGF-1 signaling by ablating IGF-1 and increasing IGF-binding protein 3, increased vSMC apoptosis, and decreased proliferation. Expression of α-actin and col3a1 genes was strongly attenuated by macrophage-conditioned medium, whereas expression of matrix-degrading enzymes was increased. Importantly, all of these effects could be corrected by supplementation with IGF-1. In vivo, treatment with the stable IGF-1 analog Long R3 IGF-1 in apolipoprotein E knockout mice reduced stenosis and core size, and doubled cap/core ratio in early atherosclerosis. In advanced plaques, Long R3 IGF-1 increased the vSMC content of the plaque by more than twofold and significantly reduced the rate of intraplaque hemorrhage. We believe that IGF-1 in atherosclerotic plaques may have a role in preventing plaque instability, not only by modulating smooth muscle cell turnover, but also by altering smooth muscle cell phenotype. PMID:21281823

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  1. Fibulin-2 is present in murine vascular lesions and is important for smooth muscle cell migration

    DEFF Research Database (Denmark)

    Ström, A.; Olin, A. I.; Aspberg, A.

    2006-01-01

    /hyaluronan complexes, an ECM network that has been suggested to be important during tissue repair. In this study we have analysed the presence of fibulin-2 in two different models of murine vascular lesions. We have also examined how the fibulin-2/versican network influences SMC migration. Methods: Presence of fibulin......Objective: The vascular extracellular matrix (ECM) can affect smooth muscle cell (SMC) adhesion, migration and proliferation-events that are important during the atherosclerotic process. Fibulin-2 is a member of the ECM protein family of fibulins and has been found to cross-link versican...... and is upregulated during SMC phenotypic modulation in cell culture. Moreover, treatments with peptides that block the interaction between versican and fibulin-2 inhibit SMC migration in vitro. Conclusions: Fibulin-2 can be produced by SMC as a response to injury and may participate in the ECM organisation...

  2. The ARTICO study: identification of patients at high risk of vascular recurrence after a first non-cardioembolic stroke.

    Science.gov (United States)

    Serena, Joaquín; Segura, Tomás; Roquer, Jaume; García-Gil, María; Castillo, José

    2015-03-11

    About 20% of patients with a first ischaemic stroke will experience a new vascular event within the first year. The atherosclerotic burden, an indicator of the extension of atherosclerosis in a patient, has been associated with the risk of new cardiovascular events in the general population. However, no predictive models reliably identify groups at a high risk of recurrence. The ARTICO study prospectively analysed the predictive value for the risk of recurrence of specific atherosclerotic markers. The multicentre ARTICO study included 620 consecutive independent patients older than 60 years suffering from a first non-cardioembolic stroke. We analysed classical stroke risk factors; duplex study of supraaortic trunk including intima-media thickness (IMT) measurement; quantification of internal carotid (ICA) stenosis; number, morphology and surface characteristics of carotid plaques; ankle brachial index (ABI); and the presence of microalbuminuria. Patients were followed up at 6 and 12 months after inclusion. The primary end-point was death or major cardiovascular events. Any vascular event or death at 12 months occurred in 78 (13.8%) patients. In 40 (7.1%) of these the vascular event was a stroke recurrence. Weight, history of diabetes mellitus, history of symptomatic PAD, ABI 50%) were associated with a higher risk of vascular events on follow-up in the bivariate analysis. In the final Cox regression analysis, body mass index (BMI), systolic blood pressure, history of diabetes mellitus, symptomatic PAD (HR, 2.76; 95% CI, 1.10-6.95; p=0.03), and particularly patients with both ICA stenosis >50% and PAD (HR 4.52; 95% CI, 2.14-9.53; p50% nor isolated abnormal ABI remained associated with an increased risk of recurrence in comparison with the whole population. Symptomatic PAD identifies a high risk group of vascular recurrence after a first non-cardioembolic stroke. The associated increased risk was particularly high in patients with both ICA stenosis and either

  3. 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.

  4. 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

  5. Initial stress in biomechanical models of atherosclerotic plaques

    NARCIS (Netherlands)

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

    2011-01-01

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

  6. High wall shear stress and spatial gradients in vascular pathology: a review.

    Science.gov (United States)

    Dolan, Jennifer M; Kolega, John; Meng, Hui

    2013-07-01

    Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bert Rutten

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

  10. 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.

  11. Metabolic syndrome predicts vascular changes in whole body magnetic resonance imaging in patients with long standing diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Findeisen Hannes M

    2010-08-01

    Full Text Available Abstract Background Although diabetic patients have an increased rate of cardio-vascular events, there is considerable heterogeneity with respect to cardiovascular risk, requiring new approaches to individual cardiovascular risk factor assessment. In this study we used whole body-MR-angiography (WB-MRA to assess the degree of atherosclerosis in patients with long-standing diabetes and to determine the association between metabolic syndrome (MetS and atherosclerotic burden. Methods Long standing (≥10 years type 1 and type 2 diabetic patients (n = 59; 31 males; 63.3 ± 1.7 years were examined by WB-MRA. Based on the findings in each vessel, we developed an overall score representing the patient's vascular atherosclerotic burden (MRI-score. The score's association with components of the MetS was assessed. Results The median MRI-score was 1.18 [range: 1.00-2.41] and MetS was present in 58% of the cohort (type 2 diabetics: 73%; type 1 diabetics: 26%. Age (p = 0.0002, HDL-cholesterol (p = 0.016, hypertension (p = 0.0008, nephropathy (p = 0.0093, CHD (p = 0.001 and MetS (p = 0.0011 were significantly associated with the score. Adjusted for age and sex, the score was significantly (p = 0.02 higher in diabetics with MetS (1.450 [1.328-1.572] compared to those without MetS (1.108 [0.966-1.50]. The number of MetS components was associated with a linear increase in the MRI-score (increase in score: 0.09/MetS component; r2 = 0.24, p = 0.038. Finally, using an established risk algorithm, we found a significant association between MRI-score and 10-year risk for CHD, fatal CHD and stroke. Conclusion In this high-risk diabetic population, WB-MRA revealed large heterogeneity in the degree of systemic atherosclerosis. Presence and number of traits of the MetS are associated with the extent of atherosclerotic burden. These results support the perspective that diabetic patients are a heterogeneous population with increased but varying prevalence of atherosclerosis

  12. Metabolic syndrome predicts vascular changes in whole body magnetic resonance imaging in patients with long standing diabetes mellitus.

    Science.gov (United States)

    Findeisen, Hannes M; Weckbach, Sabine; Stark, Renée G; Reiser, Maximilian F; Schoenberg, Stefan O; Parhofer, Klaus G

    2010-08-30

    Although diabetic patients have an increased rate of cardio-vascular events, there is considerable heterogeneity with respect to cardiovascular risk, requiring new approaches to individual cardiovascular risk factor assessment. In this study we used whole body-MR-angiography (WB-MRA) to assess the degree of atherosclerosis in patients with long-standing diabetes and to determine the association between metabolic syndrome (MetS) and atherosclerotic burden. Long standing (> or = 10 years) type 1 and type 2 diabetic patients (n = 59; 31 males; 63.3 +/- 1.7 years) were examined by WB-MRA. Based on the findings in each vessel, we developed an overall score representing the patient's vascular atherosclerotic burden (MRI-score). The score's association with components of the MetS was assessed. The median MRI-score was 1.18 [range: 1.00-2.41] and MetS was present in 58% of the cohort (type 2 diabetics: 73%; type 1 diabetics: 26%). Age (p = 0.0002), HDL-cholesterol (p = 0.016), hypertension (p = 0.0008), nephropathy (p = 0.0093), CHD (p = 0.001) and MetS (p = 0.0011) were significantly associated with the score. Adjusted for age and sex, the score was significantly (p = 0.02) higher in diabetics with MetS (1.450 [1.328-1.572]) compared to those without MetS (1.108 [0.966-1.50]). The number of MetS components was associated with a linear increase in the MRI-score (increase in score: 0.09/MetS component; r2 = 0.24, p = 0.038). Finally, using an established risk algorithm, we found a significant association between MRI-score and 10-year risk for CHD, fatal CHD and stroke. In this high-risk diabetic population, WB-MRA revealed large heterogeneity in the degree of systemic atherosclerosis. Presence and number of traits of the MetS are associated with the extent of atherosclerotic burden. These results support the perspective that diabetic patients are a heterogeneous population with increased but varying prevalence of atherosclerosis and risk.

  13. Endothelial dysfunction, vascular disease and stroke: the ARTICO study.

    Science.gov (United States)

    Roquer, J; Segura, T; Serena, J; Castillo, J

    2009-01-01

    Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Its presence is a risk factor for the development of clinical events, and may represent a marker of atherothrombotic burden. Also, endothelial dysfunction contributes to enhanced plaque vulnerability, may trigger plaque rupture, and favors thrombus formation. The assessment of endothelial vasomotion is a useful marker of atherosclerotic vascular disease. There are different methods to assess endothelial function: endothelium-dependent vasodilatation brachial flow-mediated dilation, cerebrovascular reactivity to L-arginine, and the determination of some biomarkers such as microalbuminuria, platelet function, and C-reactive protein. Endothelial dysfunction has been observed in stroke patients and has been related to stroke physiopathology, stroke subtypes, clinical severity and outcome. Resting ankle-brachial index (ABI) is also considered an indicator of generalized atherosclerosis, and a low ABI is associated with an increase in stroke incidence in the elderly. Despite all these data, there are no studies analyzing the predictive value of ABI for new cardiovascular events in patients after suffering an acute ischemic stroke. ARTICO is an ongoing prospective, observational, multicenter study being performed in 50 Spanish hospitals. The aim of the ARTICO study is to evaluate the prognostic value of a pathological ABI (ARTICO study will increase the knowledge of patient outcome after ischemic stroke and may help to improve our ability to detect patients at high risk of stroke recurrence or major cardiovascular events. (c) 2009 S. Karger AG, Basel.

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

    Science.gov (United States)

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

    2003-09-01

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

  15. Combined Atherosclerotic Lesions in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    L.V. Khimion

    2016-04-01

    Full Text Available Introduction. Significant prevalence of atherosclerosis and its complications in patients with type 2 diabetes mellitus (DM determines the need for further investigations of existing risk factors. Objective. To determine the effect of various risk factors on the development of atherosclerotic lesions in patients with type 2 DM. Materials and methods. The average levels of systolic blood pressure (SBP, HbA1c, high sensitivity C-reactive protein (hsCRP, uric acid (UA, low density lipoprotein cholesterol (LDL–C in the blood serum and the score by the anxiety and depression scale (HADRS compared to the evaluation of ultrasound data of atherosclerotic lesion of the carotid arteries (intima-media thickness ≥ 0.9 mm or the presence of atherosclerotic plaques and lower limb arteries (ankle-brachial index ≤ 0.9 were analyzed in 122 patients with type 2 DM (66 women, 56 men, mean age — 55.0 (49.8–62.0 years during 5-year follow-up. Statistical analysis was performed using IBM SPSS Statistics 20. Results. During the study, patients were divided into 3 groups: group 1 — 48 people with atherosclerotic lesions of the carotid arteries and lower extremities, group 2 — 47 individuals with atherosclerosis of the carotid arteries, group 3 — 27 people with no signs of atherosclerotic lesion. It was found that in group 1 patients, the average levels of SBP (141.7 (132.1–152.9 mmHg, HbA1c (9.2 (8.2–9.9 %, hsCRP (5.8 (4.2–6.9 mg/L, UA (358.1 (302.4–396.1 μmol/L, LDL–C (4.1 (3.6–5.2 mmol/L, a score by HADRS (16.0 (9.0–18.8 points were significantly higher compared to that of in group 3 (SBP — 136.7 (128.3–143.3 mmHg, HbA1c — 7.7 (7.0–8.4 %, hsCRP — 2.7 (1.1–3.3 mg/L, UA — 276.8 (227.0–316.0 μmol/L, LDL–C — 3.3 (3.0–4.0 mmol/L, a score by HADRS (8.0 (7.0–10.0 points (p < 0.05. The average levels of HbA1c and hsCRP in group 1 patients were significantly higher compared with that of in group 2 (HbA1c — 8.7 (7.6–9

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    Zhang, Y.; Wu, Z.

    2000-01-01

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

  19. The role of shear stress and arteriogenesis in maintaining vascular homeostasis and preventing cerebral atherosclerosis

    Directory of Open Access Journals (Sweden)

    David Della-Morte

    2015-01-01

    Full Text Available Shear stress (SS is a biomechanical force that is determined by blood flow, vessel geometry, and fluid viscosity. Although a wide range of known vascular risk factors promote development of atherosclerosis, atherosclerotic changes occur predominately at specific sites within the arterial tree, suggesting a critical role for local factors within the vasculature. Atherosclerotic lesions develop predominantly at branches, bends, and bifurcations in the arterial tree because these sites are exposed to low or disturbed blood flow and low SS. Low SS predisposes arteries to atherosclerosis by causing endothelial dysfunction. A natural system of preexisting cerebral collateral arteries protects against ischemia by bypassing sites of arterial occlusion through a mechanism of arteriogenesis. The main trigger for arteriogenesis is impaired vascular homeostasis (VH in response to local changes in SS induced by ischemia. VH is a critical process for maintaining the physiological function of cerebral circulation. It is regulated through a complex biological system of blood flow hemodynamic and physiological responses to flow changes. Restoration of VH by increasing arteriogenesis and SS may provide a novel therapeutic target for stroke, especially in the elderly, who are more prone to VH impairment. In this review article, we discuss the mechanisms and structures necessary to maintain VH in brain circulation, the role of SS, and risk factors leading to atherosclerosis, including the effects of aging. We also discuss arteriogenesis as an adaptive and protective process in response to ischemic injury, the imaging techniques currently available to evaluate arterogenesis such as magnetic resonance imaging/positron emission tomography (MRI/PET, and the potential therapeutic approaches against ischemic injury that target arteriogenesis.

  20. 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.

  1. Association of Metabolic Syndrome with the Cardioankle Vascular Index in Asymptomatic Korean Population

    Science.gov (United States)

    Nam, Su-Hyun; Lee, Yun-Ah; Rho, Jun-Seung

    2015-01-01

    Aim. Metabolic syndrome is characterized by a cluster of atherosclerotic cardiovascular risk factors. The cardioankle vascular index (CAVI) reflects arterial stiffness and may be used as an indicator of atherosclerotic cardiovascular disease. In this study, we investigated the association of CAVI with metabolic syndrome. Methods. A total of 1,144 adults were included in this study. We measured CAVIs and examined blood samples to identify metabolic syndrome according to WHO Asia Pacific criteria and NCEP-ATPIII criteria. AST, ALT, r-GTP, BUN, creatinine, high sensitivity C-reactive protein, and uric acid were also measured. Results. CAVI values were significantly higher in subjects with metabolic syndrome than those without metabolic syndrome and increased according to the number of metabolic syndrome components present. Subjects with high fasting blood sugar levels or high blood pressure showed high CAVI values. Multiple regression analysis showed that age, sex, diastolic blood pressure, and uric acid were independent predictors of CAVI. Conclusion. Subjects with metabolic syndrome had high CAVIs, which indicated arterial stiffness, and were closely associated with an increase in the number of metabolic risk factors. The individual risk factors for metabolic syndrome have the synergistic effect of elevating arterial stiffness in asymptomatic Korean population. PMID:26273666

  2. High-resolution vessel wall MRI for the evaluation of intracranial atherosclerotic disease

    Energy Technology Data Exchange (ETDEWEB)

    De Havenon, Adam [University of Utah, Department of Neurology, Salt Lake City, UT (United States); Mossa-Basha, Mahmud [University of Washington, Department of Radiology, Seattle, WA (United States); Shah, Lubdha; Kim, Seong-Eun; Parker, Dennis; McNally, J.S. [University of Utah, Department of Radiology, Salt Lake City, UT (United States); Park, Min [University of Utah, Department of Neurosurgery, Salt Lake City, UT (United States)

    2017-12-15

    High-resolution vessel wall MRI (vwMRI) of the intracranial arteries is an emerging diagnostic imaging technique with the goal of evaluating vascular pathology. vwMRI sequences have high spatial resolution and directly image the vessel wall by suppressing blood signal. With vwMRI, it is possible to identify distinct morphologic and enhancement patterns of atherosclerosis that can provide important information about stroke etiology and recurrence risk. We present a review of vwMRI research in relation to intracranial atherosclerosis, with a focus on the relationship between ischemic stroke and atherosclerotic plaque T1 post-contrast enhancement or plaque/vessel wall morphology. The goal of this review is to provide readers with the most current understanding of the reliability, incidence, and importance of specific vwMRI findings in intracranial atherosclerosis, to guide their interpretation of vwMRI research, and help inform clinical interpretation of vwMRI. We will also provide a translational perspective on the existing vwMRI literature and insight into future vwMRI research questions and objectives. With increased use of high field strength MRI, powerful gradients, and improved pulse sequences, vwMRI will become standard-of-care in the diagnosis and prognosis of patients with cerebrovascular disease, making a firm grasp of its strengths and weakness important for neuroimagers. (orig.)

  3. High-resolution vessel wall MRI for the evaluation of intracranial atherosclerotic disease

    International Nuclear Information System (INIS)

    De Havenon, Adam; Mossa-Basha, Mahmud; Shah, Lubdha; Kim, Seong-Eun; Parker, Dennis; McNally, J.S.; Park, Min

    2017-01-01

    High-resolution vessel wall MRI (vwMRI) of the intracranial arteries is an emerging diagnostic imaging technique with the goal of evaluating vascular pathology. vwMRI sequences have high spatial resolution and directly image the vessel wall by suppressing blood signal. With vwMRI, it is possible to identify distinct morphologic and enhancement patterns of atherosclerosis that can provide important information about stroke etiology and recurrence risk. We present a review of vwMRI research in relation to intracranial atherosclerosis, with a focus on the relationship between ischemic stroke and atherosclerotic plaque T1 post-contrast enhancement or plaque/vessel wall morphology. The goal of this review is to provide readers with the most current understanding of the reliability, incidence, and importance of specific vwMRI findings in intracranial atherosclerosis, to guide their interpretation of vwMRI research, and help inform clinical interpretation of vwMRI. We will also provide a translational perspective on the existing vwMRI literature and insight into future vwMRI research questions and objectives. With increased use of high field strength MRI, powerful gradients, and improved pulse sequences, vwMRI will become standard-of-care in the diagnosis and prognosis of patients with cerebrovascular disease, making a firm grasp of its strengths and weakness important for neuroimagers. (orig.)

  4. Control of atherosclerotic plaque vulnerability: insights from transgenic mice

    NARCIS (Netherlands)

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

    2008-01-01

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

  5. Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall

    Directory of Open Access Journals (Sweden)

    Michela Zanetti

    2015-01-01

    Full Text Available Omega-3 polyunsaturated fatty acids (n-3 PUFA consumption is associated with reduced cardiovascular disease risk. Increasing evidence demonstrating a beneficial effect of n-3 PUFA on arterial wall properties is progressively emerging. We reviewed the recent available evidence for the cardiovascular effects of n-3 PUFA focusing on structural and functional properties of the vascular wall. In experimental studies and clinical trials n-3 PUFA have shown the ability to improve arterial hemodynamics by reducing arterial stiffness, thus explaining some of its cardioprotective properties. Recent studies suggest beneficial effects of n-3 PUFA on endothelial activation, which are likely to improve vascular function. Several molecular, cellular, and physiological pathways influenced by n-3 PUFA can affect arterial wall properties and therefore interfere with the atherosclerotic process. Although the relative weight of different physiological and molecular mechanisms and the dose-response on arterial wall properties have yet to be determined, n-3 PUFA have the potential to beneficially impact arterial wall remodeling and cardiovascular outcomes by targeting arterial wall stiffening and endothelial dysfunction.

  6. PET/MR Imaging in Vascular Disease

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Pedersen, Sune Folke; Kjær, Andreas

    2016-01-01

    For imaging of atherosclerotic disease, lumenography using computed tomography, ultrasonography, or invasive angiography is still the backbone of evaluation. However, these methods are less effective to predict the likelihood of future thromboembolic events caused by vulnerability of plaques. PET...... through data and arguments that support increased use of PET/MR imaging in atherosclerotic imaging....

  7. Type 1 diabetes promotes disruption of advanced atherosclerotic lesions in LDL receptor-deficient mice

    OpenAIRE

    Johansson, Fredrik; Kramer, Farah; Barnhart, Shelley; Kanter, Jenny E.; Vaisar, Tomas; Merrill, Rachel D.; Geng, Linda; Oka, Kazuhiro; Chan, Lawrence; Chait, Alan; Heinecke, Jay W.; Bornfeldt, Karin E.

    2008-01-01

    Cardiovascular disease, largely because of disruption of atherosclerotic lesions, accounts for the majority of deaths in people with type 1 diabetes. Recent mouse models have provided insights into the accelerated atherosclerotic lesion initiation in diabetes, but it is unknown whether diabetes directly worsens more clinically relevant advanced lesions. We therefore used an LDL receptor-deficient mouse model, in which type 1 diabetes can be induced at will, to investigate the effects of diabe...

  8. Invasive assessment of renal artery atherosclerotic disease and resistant hypertension before renal sympathetic denervation.

    Science.gov (United States)

    Ribichini, Flavio; Pighi, Michele; Zivelonghi, Carlo; Gambaro, Alessia; Valvo, Enrico; Lupo, Antonio; Vassanelli, Corrado

    2013-01-01

    Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. The presence of a renal artery stenosis may be both a cause of secondary hypertension and a contraindication to RSD if a renal artery stent is implanted; therefore, the definition of the functional importance of a renal artery stenosis in a patient with refractory hypertension is crucial. We describe the imaging and functional intravascular assessment of an angiographically severe stenosis of the renal artery in a patient with severe refractory hypertension, by means of intravascular ultrasound (IVUS), and measurement of the translesional pressure gradient with a pressure wire. Pressure wire examination excluded any severity of the stenosis, and IVUS showed the presence of a dissected plaque that resolved spontaneously after 3 months of intensive medical therapy and high-dose statin. Subsequently the patient was treated with RSD, achieving a significant effect on blood pressure control. Intravascular imaging and functional assessment of renal artery anatomy in patients with atherosclerotic disease may prove particularly suited to patients with refractory hypertension and multilevel vascular disease who are considered for endovascular therapies, either renal artery stenting or RSD.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-10-08

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

  11. Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.

    Science.gov (United States)

    Hwang, Hwan-Jin; Jung, Tae Woo; Hong, Ho Cheol; Choi, Hae Yoon; Seo, Ji-A; Kim, Sin Gon; Kim, Nan Hee; Choi, Kyung Mook; Choi, Dong Seop; Baik, Sei Hyun; Yoo, Hye Jin

    2013-01-01

    Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs) treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO) level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS)-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB) levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1), the crucial inflammatory molecules known to aggravate atherosclerosis. Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.

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

    Science.gov (United States)

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

    2016-02-01

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

  13. Primary infragenicular angioplasty for diabetic neuroischemic foot ulcers following the angiosome distribution: a new paradigm for the vascular interventionist?

    Directory of Open Access Journals (Sweden)

    Alexandrescu V

    2011-08-01

    Full Text Available Vlad Alexandrescu1, Gerard Hubermont21Department of Vascular Surgery, Princess Paola Hospital, Marche- en-Famenne, Belgium; 2Department of Diabetology, Princess Paola Hospital, Marche-en-Famenne and Sainte-Thérèse Hospital, Bastogne, BelgiumAbstract: The angiosome principle was first described by Jan Taylor in 1987 in the plastic reconstructive surgery field, providing useful information on the vascular anatomy of the human body. Specifically concerning foot and ankle pathology, it may help the clinician to select better vascular access and specific strategies for revascularization. This knowledge may be particularly beneficial when treating diabetic neuroischemic foot wounds associated with particularly aggressive atherosclerotic disease and a poor collateral circulation. The implementation of angiosome-based strategies in diabetic infragenicular vascular reconstruction may afford encouraging wound healing and limb preservation rates using both bypass and endovascular techniques. The minimal invasiveness of these novel strategies enables us to perform more specific and more distal tibial and/or foot arterial reconstructions, in one or multiple targeted vessels. This paper reviews the available literature on this revascularization strategy and focuses on the potential benefit of angiosome-guided primary angioplasty for diabetic ischemic foot ulcers.Keywords: critical limb ischemia, diabetic foot, limb salvage, angiosomes, angioplasty

  14. Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.

    Directory of Open Access Journals (Sweden)

    Hwan-Jin Hwang

    Full Text Available OBJECTIVE: Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. METHOD AND RESULTS: Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α and monocyte chemo-attractant protein-1 (MCP-1, the crucial inflammatory molecules known to aggravate atherosclerosis. CONCLUSION: Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.

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

    Science.gov (United States)

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

    2012-09-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

  18. Utility of the indium 111-labeled human immunoglobulin G scan for the detection of focal vascular graft infection

    International Nuclear Information System (INIS)

    LaMuraglia, G.M.; Fischman, A.J.; Strauss, H.W.; Keech, F.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Rubin, R.H.

    1989-01-01

    The ability to diagnose and localize vascular graft infections has been a major challenge. Recent studies in animal models and humans with focal bacterial infection have shown that radiolabeled, polyclonal, human immunoglobulin G accumulates at the site of inflammation and can serve as the basis for an imaging technique. This study investigated this new technique for the diagnosis and localization of vascular graft infections. Twenty-five patients with suspected vascular infections involving grafts (22), atherosclerotic aneurysms (2), and subclavian vein thrombophlebitis (1) were studied. Gamma camera images of the suspected area were obtained between 5 and 48 hours after intravenous administration of 1.5 to 2.0 mCi (56 to 74 mBq) of indium 111-labeled, human, polyclonal immunoglobulin G. Scan results were interpreted without clinical information about the patient and were subsequently correlated with surgical findings, other imaging modalities, and/or clinical follow-up. In 10 of 10 patients found to have positive scan results, localized infections were confirmed at the involved sites. In 14 of 15 patients whose scan results were interpreted as negative, no vascular infections were identified at follow-up. The patient with false-negative results and recurrent bacteremia from an aortoduodenal fistula was found to have a negative scan outcome at a time when his disease was quiescent. These data suggest that nonspecific, human, indium 111-labeled immunoglobulin G scanning can be a useful noninvasive means of localizing vascular infections

  19. Aortic VCAM-1: an early marker of vascular inflammation in collagen-induced arthritis.

    Science.gov (United States)

    Denys, Anne; Clavel, Gaëlle; Lemeiter, Delphine; Schischmanoff, Olivier; Boissier, Marie-Christophe; Semerano, Luca

    2016-05-01

    Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen-induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen-induced arthritis was induced with intradermal injection of chicken type-II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS) and interleukin-17 were analysed by quantitative RT-PCR. Vascular cell adhesion molecule-1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen-induced arthritis was associated with increased expression of VCAM-1, independent of diet. VCAM-1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM-1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large-vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  1. Sample sequencing of vascular plants demonstrates widespread conservation and divergence of microRNAs.

    Science.gov (United States)

    Chávez Montes, Ricardo A; de Fátima Rosas-Cárdenas, Flor; De Paoli, Emanuele; Accerbi, Monica; Rymarquis, Linda A; Mahalingam, Gayathri; Marsch-Martínez, Nayelli; Meyers, Blake C; Green, Pamela J; de Folter, Stefan

    2014-04-23

    Small RNAs are pivotal regulators of gene expression that guide transcriptional and post-transcriptional silencing mechanisms in eukaryotes, including plants. Here we report a comprehensive atlas of sRNA and miRNA from 3 species of algae and 31 representative species across vascular plants, including non-model plants. We sequence and quantify sRNAs from 99 different tissues or treatments across species, resulting in a data set of over 132 million distinct sequences. Using miRBase mature sequences as a reference, we identify the miRNA sequences present in these libraries. We apply diverse profiling methods to examine critical sRNA and miRNA features, such as size distribution, tissue-specific regulation and sequence conservation between species, as well as to predict putative new miRNA sequences. We also develop database resources, computational analysis tools and a dedicated website, http://smallrna.udel.edu/. This study provides new insights on plant sRNAs and miRNAs, and a foundation for future studies.

  2. 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.

  3. A practical method for quantifying atherosclerotic lesions in rabbits.

    Science.gov (United States)

    Zhang, C; Zheng, H; Yu, Q; Yang, P; Li, Y; Cheng, F; Fan, J; Liu, E

    2010-01-01

    The rabbit has been widely used for the study of human atherosclerosis; however, the method for analysis of the atherosclerotic lesions has not been standardized between laboratories. The present study reports a practical method for quantifying the changes that occur in aortic atherosclerosis of rabbits. Male Japanese white rabbits were fed with either a standard chow or a diet containing 10% fat and 0.3% cholesterol for 16 weeks. Plasma concentrations of glucose, insulin, total cholesterol, triglycerides and high-density lipoprotein were measured. Aortic atherosclerotic lesions were assessed in quantitative fashion using an image analysis system that measured (1) the gross area of the entire aorta affected by atherosclerosis as defined by Sudan IV staining, (2) the microscopical intimal lesion defined by the elastic van Gieson stain and (3) the infiltration of macrophages and smooth muscle cell proliferation as determined immunohistochemically. The rabbits developed severe aortic atherosclerosis without apparent abnormality of glucose metabolism. The quantitative method described here will be useful for the further investigation of atherosclerosis in rabbits. Copyright 2009 Elsevier Ltd. All rights reserved.

  4. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2009-08-01

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

  7. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  10. Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques

    NARCIS (Netherlands)

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

    2012-01-01

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

  11. Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

    Science.gov (United States)

    Lau, Kui Kai; Wong, Yuen Kwun; Chan, Yap Hang; Teo, Kay Cheong; Chan, Koon Ho; Wai Li, Leonard Sheung; Cheung, Raymond Tak Fai; Siu, Chung Wah; Ho, Shu Leong; Tse, Hung Fat

    2014-07-01

    Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all Parea under receiver operating characteristic curve (AUC) 0.69 ± 0.03, PAUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Quantum correlated imaging is a promising new technique in medical imaging

    Institute of Scientific and Technical Information of China (English)

    Nan Zhang; Zhaohua Yang

    2017-01-01

    Cardio-cerebral vascular diseases are common and frequently occurring serious diseases that threaten humans. In recent years, Digital Subtraction Angiography (DSA) has played a vital role in the diagnosis and treatment of cardio-cerebral vascular diseases. However, DSA is not able to visualize intravascular structures in real time, and it is especially difficult to evaluate each layer of the vascular wall and the composition of atherosclerotic plaques with DSA. Quantum correlated imaging is a new technique that can be used to perform real-time online imaging of intravascular flow, vascular wall structure, and atherosclerotic plaque composition. Quantum correlated imaging is a promising new technique that will soon be used in the diagnosis and treatment of cardio-cerebral vascular diseases.

  13. Interventional therapy of atherosclerotic renal artery occlusion

    International Nuclear Information System (INIS)

    Li Jian; Xu Ke; Xiao Liang

    2009-01-01

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

  14. Impact of the individual components of the metabolic syndrome and their different combinations on the prevalence of atherosclerotic vascular disease in type 2 diabetes: the Diabetes in Germany (DIG study

    Directory of Open Access Journals (Sweden)

    Benke Inge

    2007-04-01

    Full Text Available Abstract Background One of the major controversies surrounding the metabolic syndrome (MetS in type 2 diabetes is whether its single components act synergistically as risk factors for atherosclerotic vascular disease (AVD. We aimed to answer this by evaluating the relationship, and its various combinations to AVD in comparison to single traits in a population-based study with type 2 diabetes in Germany. Methods and results 4020 unselected patients with type 2 diabetes aged 35 – 80 years. MetS was: diabetes plus ≥ 2 traits of the MetS by AHA/NHBLI definition. AVD was: history of myocardial infarction and/or coronary revascularization and/or stroke. The occurrence of AVD in relation to overall MetS/single traits/combinations was presented as OR (95% CI. Multiple logistic regression, including established cardiovascular risk factors, modeled their associations. The prevalence of overall MetS was 74.4% and the OR for AVD was 1.41 (1.12–1.78, which however was higher for hypertension as single trait (OR 4.76. Different combinations of MetS presented a wide range of ORs (0.47 to 10.90 and strong sex differences. Some clusters of MetS including hypertension and low HDL-cholesterol presented a higher risk factor than single traits or their sum, whereas the others out of 11 possible carried no increased AVD risk. Multiple logistic regression showed independent association between AVD and overall MetS. Conclusion The overall MetS in type 2 diabetes comprises 11 heterogenous clusters of traits. Overall MetS increases the risk of AVD in type 2 diabetes and individual traits in some clusters with hypertension and low HDL-cholesterol may act synergistically as risk factors particularly in women.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Low-density lipoproteins cause atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  18. MR chemical shift imaging and spectroscopy of atherosclerotic plaque

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  20. Evaluation of atherosclerotic change of the aorta by enhanced computed tomography

    International Nuclear Information System (INIS)

    Takasu, Junichiro

    1990-01-01

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

  1. Bisphosphonates, atherosclerosis and vascular calcification: update and systematic review of clinical studies

    Directory of Open Access Journals (Sweden)

    Caffarelli C

    2017-10-01

    Full Text Available Carla Caffarelli,1 Andrea Montagnani,2 Ranuccio Nuti,1 Stefano Gonnelli1 1Department of Medicine, Surgery and Neuroscience, University of Siena, Italy; 2Division of Internal Medicine, General Hospital Misericordia, Grosseto, Italy Background: Epidemiologic and clinical data have suggested the existence of a biologic linkage between the bone system and the vascular system. Bisphosphonates (BPs are effective inhibitors of bone resorption and are currently considered the drugs of choice for the prevention and treatment of osteoporosis and related fractures. Data from several publications have suggested that BPs may also be effective in reducing the atherosclerotic process and vascular calcification, but the results of these studies are contrasting. This review aimed to allow a better understanding of the relationships between BPs and atherosclerosis in humans.Materials and methods: Electronic databases of Pubmed-Medline, Cochrane Library and SCOPUS from inception to June 30, 2016 were searched. The full texts of the articles potentially eligible were carefully assessed and reviewed. Finally, 20 studies were found to be eligible and were included in the systematic review. All included studies were published between 2000 and 2014.Results: In several studies, etidronate limited the progression of aortic and coronary calcification in hemodialysis patients, whereas the nitrogen-containing-BPs given orally did not significantly reduce vascular calcifications in patients with chronic kidney disease, kidney trasplant or in those with osteoporosis. Nitrogen-containing-BPs present favorable effects both on vessel wall thickness and on arterial elasticity due to both a reduction in serum lipids and the interaction of BPs with the bone tissue, with the consequent release of bone turnover markers and cytokines into the bloodstream.Conclusion: To sum up, the BPs seem to have the potential of influencing atherosclerosis and calcium homeostasis at the level of

  2. Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity

    DEFF Research Database (Denmark)

    Laugesen, Esben; Høyem, Pernille; Christiansen, Jens Sandahl

    2013-01-01

    The arterial system in diabetic patients is characterized by generalized non-atherosclerotic alterations in the vascular extracellular matrix causing increased arterial stiffness compared with subjects without diabetes. The underlying pathophysiology remains elusive. The elastin-associated extrac......The arterial system in diabetic patients is characterized by generalized non-atherosclerotic alterations in the vascular extracellular matrix causing increased arterial stiffness compared with subjects without diabetes. The underlying pathophysiology remains elusive. The elastin...

  3. HDL mimetic CER-001 targets atherosclerotic plaques in patients.

    Science.gov (United States)

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

    2016-08-01

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

  4. Irradiation of existing atherosclerotic lesions increased inflammation by favoring pro-inflammatory macrophages

    International Nuclear Information System (INIS)

    Gabriels, Karen; Hoving, Saske; Gijbels, Marion J.; Pol, Jeffrey F.; Poele, Johannes A. te; Biessen, Erik A.; Daemen, Mat J.; Stewart, Fiona A.; Heeneman, Sylvia

    2014-01-01

    Background and purpose: Recent studies have shown an increased incidence of localized atherosclerosis and subsequent cardiovascular events in cancer patients treated with thoracic radiotherapy. We previously demonstrated that irradiation accelerated the development of atherosclerosis and predisposed to an inflammatory plaque phenotype in young hypercholesterolemic ApoE −/− mice. However, as older cancer patients already have early or advanced stages of atherosclerosis at the time of radiotherapy, we investigated the effects of irradiation on the progression of existing atherosclerotic lesions in vivo. Material and methods: ApoE −/− mice (28 weeks old) received local irradiation with 14 or 0 Gy (sham-treated) at the aortic arch and were examined after 4 and 12 weeks for atherosclerotic lesions, plaque size and phenotype. Moreover, we investigated the impact of irradiation on macrophage phenotype (pro- or anti-inflammatory) and function (efferocytotic capacity, i.e. clearance of apoptotic cells) in vitro. Results: Irradiation of existing lesions in the aortic arch resulted in smaller, macrophage-rich plaques with intraplaque hemorrhage and increased apoptosis. In keeping with the latter, in vitro studies revealed augmented polarization toward pro-inflammatory macrophages after irradiation and reduced efferocytosis by anti-inflammatory macrophages. In addition, considerably more lesions in irradiated mice were enriched in pro-inflammatory macrophages. Conclusions: Irradiation of existing atherosclerotic lesions led to smaller but more inflamed plaques, with increased numbers of apoptotic cells, most likely due to a shift toward pro-inflammatory macrophages in the plaque

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  6. PPARα activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH.

    Science.gov (United States)

    Baron, Morgane; Leroyer, Aurélie S; Majd, Zouher; Lalloyer, Fanny; Vallez, Emmanuelle; Bantubungi, Kadiombo; Chinetti-Gbaguidi, Giulia; Delerive, Philippe; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne

    2011-09-01

    Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are complex pathologies characterized by lipid accumulation, chronic inflammation and extensive tissue remodelling. Microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, might not only be biomarkers, but also functional actors in these pathologies. The apoE2-KI mouse is a model of atherosclerosis and NAFLD. Activation of the nuclear receptor PPARα decreases atherosclerosis and components of non-alcoholic steatohepatitis (NASH) in the apoE2-KI mouse. (1) To determine whether MPs are present in atherosclerotic lesions, liver and plasma during atherosclerosis and NASH progression in apoE2-KI mice, and (2) to study whether PPARα activation modulates MP concentrations. ApoE2-KI mice were fed a Western diet to induce atherosclerosis and NASH. MPs were isolated from atherosclerotic lesions, liver and blood and quantified by flow cytometry. An increase of MPs was observed in the atherosclerotic lesions and in the liver of apoE2-KI mice upon Western diet feeding. PPARα activation with fenofibrate decreased MP levels in the atherosclerotic lesions in a PPARα-dependent manner, but did not influence MP concentrations in the liver. Here we report that MPs are present in atherosclerotic lesions and in the liver of apoE2-KI mice. Their concentration increased during atherosclerosis and NASH development. PPARα activation differentially modulates MP levels in a tissue-specific manner. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

    Science.gov (United States)

    Horsburgh, Karen; Reimer, Michell M; Holland, Philip; Chen, Guiquan; Scullion, Gillian; Fowler, Jill H

    2011-08-01

    Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  9. Endothelial lipase is highly expressed in macrophages in advanced human atherosclerotic lesions

    DEFF Research Database (Denmark)

    Bartels, Emil D; Nielsen, John E; Lindegaard, Marie Louise Skakkebæk

    2007-01-01

    Endothelial lipase (EL) is expressed in endothelial cells, and affects plasma lipoprotein metabolism by hydrolyzing phospholipids in HDL. To determine the cellular expression of EL mRNA and protein in human atherosclerotic lesions, we performed in situ hybridization and immunohistochemical studies...

  10. Spectral CT of carotid atherosclerotic plaque: comparison with histology

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-15

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

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

    African Journals Online (AJOL)

    McRoy

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

  12. Usefulness of abdominal aortic calcification for screening of peripheral vascular disease

    International Nuclear Information System (INIS)

    Park, Chul Hi; Kim, Jeong Ho; Choi, Soo Jin; Kim, Hyung Sik; Jin, Wook; Yang, Dal Mo

    2006-01-01

    We wanted to evaluate the value of abdominal aortic calcification (AAC), as detected on CT, as a predictor of atherosclerotic stenotic disease of the lower extremity arteries. One hundred three patients who had CT angiography performed for the evaluation of peripheral vascular disease were enrolled in this retrospective study. The volume (mm 3 ) of the AAC was measured on CT. Each lower extremity was divided into 8 segments. The extent of stenosis of the lower extremity artery was manifested as the sum of the stenosis scores for 16 segments (total stenosis score: TSS). The significant stenosis scores (SSS-50 and SSS-75) were defined as the sum of scores for the lower extremity artery segments that had significant stenosis of more than 50% and 75%, respectively. AAC was correlated to the TSS, SSS-50 and SSS-75 with using Spearman's correlation coefficient. The diagnostic performance of AAC for stenosis of a lower extremity artery of more than 50% and 75%, respectively, was evaluated by using the receiver operating characteristic (ROC) curve. The Spearman's correlation coefficients were 0.728 (AAC vs. TSS), 0.662 (AAC vs. SSS-50), and 0.602 (AAC vs. SSS-75), respectively. For significant stenosis more than 50% and 75%, the areas under the ROC curve were 0.898 and 0.866, respectively. The cutoff value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 1030 mm 3 , 87%, 88%, 89%. 86% and 87% for stenosis more than 50% and 1030 mm 3 , 87%, 80%, 79%, 88% and 84% for stenosis more than 75%, respectively. Abdominal aortic calcification detected on CT may be a useful predictor of atherosclerotic stenotic disease of lower extremity arteries

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

    DEFF Research Database (Denmark)

    Fumagalli, Stefano; Perego, Carlo; Zangari, Rosalia

    2017-01-01

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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Rita Vik

    2015-08-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

  17. Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

    Directory of Open Access Journals (Sweden)

    Long Wang

    2018-01-01

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

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

    International Nuclear Information System (INIS)

    Broisat, A.

    2005-04-01

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

  19. Peripheral vascular disease in patients with coronary artery disease

    International Nuclear Information System (INIS)

    Bashir, E. A.; Aslam, N.

    2001-01-01

    Objective: The prevalence of peripheral vascular disease (PVD) in patients with coronary artery disease (CAD) has been investigated in many different ways. It depends on the diagnostic methods used and definition of atherosclerotic manifestations in the different vascular beds. This study was carried out to determine the prevalence of PVD in the lower limbs in group of patients with CAD. Design: This is a prospective observational study. Place and duration of study: The study was conducted at Combined Military Hospital/Armed Forces institute of Cardiology, Rawalpindi, over a period of one year (January 1998 to January 1999). Subjects and methods: A total number of 200 patient (171 male and 29 females) aged 55-77 years with CAD. Diagnosed by coronary angiography were included in the study. In all patients blood pressure was recorded in both arms by sphygmomanometer and ankle systolic pressure by Doppler ultrasound. Ankle branchial index was calculated. Demographic data were obtained from the patient's hospital files. Results: The prevalence of PVD was 22.5% in patients with CAD in agreement with the results of most previous investigation. There was tendency towards increasing prevalence of PVD with more advanced CAD. Thirty patients (27%) showed evidence of triple vessel disease as compared to 13 patient (18%) with double vessel and 2 patients (1%) with single vessel disease. Conclusion: A non-invasive investigation of peripheral arterial circulation should be included early in the clinical consideration of patients with chest pain or similar symptoms suggesting coronary artery disease. Ankle systolic pressure appears to be simple and cheap technique for evaluation of results. (author)

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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.

  1. Evaluation of early atherosclerotic findings in women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Mohammadi Afshin

    2011-10-01

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

  2. Cardiovascular risk factors and collateral artery formation.

    Science.gov (United States)

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

    2009-12-01

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

  3. Penetrating atherosclerotic ulcer of the aorta: A continuing debate

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  4. Atherosclerotic lesions in humans. In situ immunophenotypic analysis suggesting an immune mediated response

    NARCIS (Netherlands)

    van der Wal, A. C.; Das, P. K.; Bentz van de Berg, D.; van der Loos, C. M.; Becker, A. E.

    1989-01-01

    The immunophenotypical features of the cellular infiltrates in different types of human atherosclerotic lesions, including diffuse intimal thickening as a potential but controversial precursor lesion, have been examined using monoclonal antibodies. Special emphasis is put on monocytes/macrophages,

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Enas R. Abdel Hameed

    2014-06-01

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

  7. The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Bilge Kocer

    2016-01-01

    Full Text Available Factors related with hyperhomocysteinemia (HHcy and the impact of HHcy in Parkinson’s disease (PD are not well understood. We investigated the factors associated with increased levels of homocysteine (Hcy and the relationship between HHcy and motor symptoms, cognitive status, and vascular risk in patients with Parkinson’s disease. Among 60 patients (29 males, 48.3% with PD, the stage of the disease, the severity of clinical symptoms, and the patients’ cognitive status were measured using a modified Hoehn and Yahr Staging Scale (mHY, Unified Parkinson’s Disease Rating Scale (UPDRS II and III, and Mini-Mental State Examination (MMSE, respectively. Patients were also noted for having dyskinesia and hallucinations. Serum vitamin B12, folic acid, and plasma Hcy ​​levels were measured. Furthermore, the presence of vascular risk factors was recorded. Finally, we investigated carotid artery intima-media thickening and stenosis using colour Doppler ultrasonography as well as the presence of ischemic lesions using brain imaging techniques. Plasma Hcy ​​levels were higher with advanced age and in males. In addition, there was an inverse relationship between Hcy ​​and vitamin B12 levels. There was no correlation between HHcy and the stage of the disease, severity of motor symptoms, cognitive status as assessed by the MMSE, vascular risk factors, carotid artery atherosclerotic findings, and ischemic brain lesions. Plasma Hcy levels may rise due to several factors in PD. However, the resulting HHcy has no significant effect on the clinical picture in terms of motor features, cognitive status, and vascular diseases.

  8. The Vascular Biology of Atherosclerosis

    National Research Council Canada - National Science Library

    Carter, R; Jones, H. P

    2006-01-01

    .... Despite this fact, most individuals are asymptomatic until many decades later. Autopsy studies of coronary arteries from healthy, young American soldiers killed during the Korean conflict revealed surprisingly advanced atherosclerotic lesions...

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    A. I. Iljina

    2005-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shuang-shuang Wang

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

  15. Bioprinting for vascular and vascularized tissue biofabrication.

    Science.gov (United States)

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

    2017-03-15

    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

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

    Science.gov (United States)

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

    2013-01-01

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

  17. Effects of High Glucose on Vascular Endothelial Growth Factor Synthesis and Secretion in Aortic Vascular Smooth Muscle Cells from Obese and Lean Zucker Rats

    Directory of Open Access Journals (Sweden)

    Mariella Trovati

    2012-07-01

    Full Text Available Type 1 diabetes is characterized by insulin deficiency, type 2 by both insulin deficiency and insulin resistance: in both conditions, hyperglycaemia is accompanied by an increased cardiovascular risk, due to increased atherosclerotic plaque formation/instabilization and impaired collateral vessel formation. An important factor in these phenomena is the Vascular Endothelial Growth Factor (VEGF, a molecule produced also by Vascular Smooth Muscle Cells (VSMC. We aimed at evaluating the role of high glucose on VEGF-A164 synthesis and secretion in VSMC from lean insulin-sensitive and obese insulin-resistant Zucker rats (LZR and OZR. In cultured aortic VSMC from LZR and OZR incubated for 24 h with D-glucose (5.5, 15 and 25 mM or with the osmotic controls L-glucose and mannitol, we measured VEGF-A164 synthesis (western, blotting and secretion (western blotting and ELISA. We observed that: (i D-glucose dose-dependently increases VEGF-A164 synthesis and secretion in VSMC from LZR and OZR (n = 6, ANOVA p = 0.002–0.0001; (ii all the effects of 15 and 25 mM D-glucose are attenuated in VSMC from OZR vs. LZR (p = 0.0001; (iii L-glucose and mannitol reproduce the VEGF-A164 modulation induced by D-glucose in VSMC from both LZR and OZR. Thus, glucose increases via an osmotic mechanism VEGF synthesis and secretion in VSMC, an effect attenuated in the presence of insulin resistance.

  18. Nanostructures to modulate vascular inflammation: Multifunctional nanoparticles for quantifiable siRNA delivery and molecular imaging

    Science.gov (United States)

    Kaneda, Megan Marie

    Early steps in the progression of inflammatory diseases such as atherosclerosis involve the recruitment of leukocytes to the vascular endothelium through the expression or up-regulation of adhesion molecules. These adhesion molecules are critical mediators of leukocyte attachment and subsequent extravasation through transendothelial migration. One of these adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) is particularly attractive as a marker of early atherosclerotic activity due to its low expression level on normal endothelium and up-regulation prior to and during the development of early lesions. With this in mind, the purpose of this thesis was to develop nanostructures for the detection and down-regulation of adhesion molecules by the vascular endothelium. To detect early inflammation we designed a perfluorocarbon nanoparticle (PFC-NP) probe, which was used for in vivo targeting of VCAM-1. Nanoparticles were detected ex vivo by the magnetic resonance (MR) signature from the fluorine core of the particle. Nanoparticles accumulated in tissues characterized by early inflammatory processes. To down-regulate VCAM-1 expression by vascular endothelial cells, cationic PFC-NP were produced through the addition of the cationic lipid 1,2-Dioleoyl-3-Trimethylammonium-Propane. Cationic PFC-NP were able to deliver anti-VCAM-1 siRNA to endothelial cells through a non-standard lipid raft mediated endocytic pathway. VCAM-1 levels were significantly reduced in treated cells indicating that this delivery mechanism may be advantageous for delivery of cargo into the cytoplasm. Using the fluorine signature from the core of the cationic PFC-NP, we were able to quantify and localize this siRNA delivery agent both in vitro and in vivo. The ability to quantify the local concentrations of these particles could be of great benefit for estimating local drug concentrations and developing new pharmacokinetic and pharmacodynamic paradigms to describe this new class of

  19. Whole body cardiovascular magnetic resonance imaging to stratify symptomatic and asymptomatic atherosclerotic burden in patients with isolated cardiovascular disease

    International Nuclear Information System (INIS)

    Weir-McCall, Jonathan R.; Duce, Suzanne L.; Gandy, Stephen J.; Matthew, Shona Z.; Martin, Patricia; Cassidy, Deirdre B.; McCormick, Lynne; Belch, Jill J. F.; Struthers, Allan D.; Colhoun, Helen M.; Houston, J. Graeme

    2016-01-01

    The aim of this study was to use whole body cardiovascular magnetic resonance imaging (WB CVMR) to assess the heart and arterial network in a single examination, so as to describe the burden of atherosclerosis and subclinical disease in participants with symptomatic single site vascular disease. 64 patients with a history of symptomatic single site vascular disease (38 coronary artery disease (CAD), 9 cerebrovascular disease, 17 peripheral arterial disease (PAD)) underwent whole body angiogram and cardiac MR in a 3 T scanner. The arterial tree was subdivided into 31 segments and each scored according to the degree of stenosis. From this a standardised atheroma score (SAS) was calculated. Cine and late gadolinium enhancement images of the left ventricle were obtained. Asymptomatic atherosclerotic disease with greater than 50 % stenosis in arteries other than that responsible for their presenting complain was detected in 37 % of CAD, 33 % of cerebrovascular and 47 % of PAD patients. Unrecognised myocardial infarcts were observed in 29 % of PAD patients. SAS was significantly higher in PAD patients 24 (17.5-30.5) compared to CAD 4 (2–11.25) or cerebrovascular disease patients 6 (2-10) (ANCOVA p < 0.001). Standardised atheroma score positively correlated with age (β 0.36 p = 0.002), smoking status (β 0.34 p = 0.002), and LV mass (β -0.61 p = 0.001) on multiple linear regression. WB CVMR is an effective method for the stratification of cardiovascular disease. The high prevalence of asymptomatic arterial disease, and silent myocardial infarctions, particularly in the peripheral arterial disease group, demonstrates the importance of a systematic approach to the assessment of cardiovascular disease

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  1. 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.

  2. Impact of Hydroxychloroquine on Atherosclerosis and Vascular Stiffness in the Presence of Chronic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Ashutosh M Shukla

    Full Text Available Cardiovascular disease is the largest cause of morbidity and mortality among patients with chronic kidney disease (CKD and end-stage kidney disease, with nearly half of all deaths attributed to cardiovascular disease. Hydroxychloroquine (HCQ, an anti-inflammatory drug, has been shown to have multiple pleiotropic actions relevant to atherosclerosis. We conducted a proof-of-efficacy study to evaluate the effects of hydroxychloroquine in an animal model of atherosclerosis in ApoE knockout mice with and without chronic kidney disease. Forty male, 6-week-old mice were divided into four groups in a 2 x 2 design: sham placebo group; sham treatment group; CKD placebo group; and CKD treatment group. CKD was induced by a two-step surgical procedure. All mice received a high-fat diet through the study duration and were sacrificed after 16 weeks of therapy. Mice were monitored with ante-mortem ultrasonic echography (AUE for atherosclerosis and vascular stiffness and with post-mortem histology studies for atherosclerosis. Therapy with HCQ significantly reduced the severity of atherosclerosis in CKD mice and sham treated mice. HCQ reduced the area of aortic atherosclerosis on en face examination by approximately 60% in HCQ treated groups compared to the non-treated groups. Additionally, therapy with HCQ resulted in significant reduction in vascular endothelial dysfunction with improvement in vascular elasticity and flow patterns and better-preserved vascular wall thickness across multiple vascular beds. More importantly, we found that presence of CKD had no mitigating effect on HCQ's anti-atherosclerotic and vasculoprotective effects. These beneficial effects were not due to any significant effect of HCQ on inflammation, renal function, or lipid profile at the end of 16 weeks of therapy. This study, which demonstrates structural and functional protection against atherosclerosis by HCQ, provides a rationale to evaluate its use in CKD patients. Further studies

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

    International Nuclear Information System (INIS)

    Yamashita, Atsushi; Zhao, Yan; Zhao, Songji

    2013-01-01

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

  4. 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

  5. Current techniques for the investigation of vulnerable atherosclerotic plaques

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  6. Early experience of endovascular treatment of peripheral vascular disease

    International Nuclear Information System (INIS)

    Ashraf, T.; Yousuf, K.; Karim, M.T.

    2015-01-01

    Atherosclerotic peripheral arterial disease (PAD) is prevalent affecting up to 16% of the population aged 55 years or older. Endovascular intervention for the treatment of limb ischemia has become the first line therapy but in Pakistan it is in embryonic stage due to dearth of trained persons and dedicated centres. This study was conducted to evaluate procedural success and early outcome of endovascular treatment of peripheral vascular disease. Methods: A prospective single arm multicentre study was conducted at the National Institute of Cardiovascular Disease and National Medical Centre, Karachi, Pakistan from January 2013 to June 2014. A total of 25 patients were enrolled in the study that underwent endovascular treatment. Out of 25 patients 23 (92%) had critical limb ischemia (CLI) as per TASC II classification (A to D) and 2 (8%) had carotid lesion with history of TIA. Patients of acute limb ischemia and stroke were excluded. Ankle brachial index (ABI) was classified as normal (0.9-1.3), mild (0.7-0.9), moderate (0.4-0.69), severe (<0.4). Outcome was taken as immediate success and symptoms, amputation of limb among CLI patients and incidence of stroke in patients with carotid artery lesion at end of six months. Results: Among aortoiliac, femoropopliteal and tibioperoneal lesions, tibioperoneal lesions at six months were found to be more symptomatic 6 (86%) and amputation 4 (57%). Two carotid lesions at follow up were asymptomatic without stroke. Conclusion: Endovascular treatment of peripheral vascular lesions, i.e., aortoiliac, femoropopliteal tibioperoneal and carotid lesions were satisfactory in immediate outcome. Tibioperoneal lesions were more symptomatic and limb amputation at six months. (author)

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

    Science.gov (United States)

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

    2008-08-01

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

  8. Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

    Directory of Open Access Journals (Sweden)

    Ning Ma

    Full Text Available OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5% with acute thrombosis, 5 patients (1.8% with subacute thrombosis, 17 patients (6.2% with stroke, and 2 death (0.7% in low-dose aspirin group, compared with no patient (0% with acute thrombosis, 2 patient (2.1% with subacute thrombosis, 6 patients (6.2% with stroke, and 2 death (2.1% in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

    Thyberg, J

    1998-07-01

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

  12. Malnutrition and its association with inflammation and vascular disease in children on maintenance dialysis.

    Science.gov (United States)

    Canpolat, Nur; Caliskan, Salim; Sever, Lale; Tasdemir, Mehmet; Ekmekci, Ozlem Balcı; Pehlivan, Gulseren; Shroff, Rukshana

    2013-11-01

    Malnutrition is associated with both inflammation and atherosclerotic cardiovascular disease in adults with chronic kidney disease. We studied the prevalence of malnutrition and its possible associations with inflammation and vascular disease in children on chronic dialysis. Thirty-three patients on maintenance dialysis (18 peritoneal dialysis, 15 hemodialysis) and 19 age- and gender- matched healthy controls were studied. Nutritional status was assessed by anthropometric measurements including body mass index (BMI), upper arm measurements, multifrequency bioimpedance analysis (BIA) and serum levels of albumin, prealbumin, and cholesterol. Inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. The carotid artery intima thickness (cIMT) was measured to assess vascular disease. Compared with healthy children, patients had lower anthropometric measurements (P Malnutrition was present in 8 (24%) and lower BIA-based fat mass was independently associated with higher IL-6 levels (P = 0.035). An increased cIMT was present in 16 (48.5%); however, there was no difference in cIMT-SDS between patients with and without malnutrition. Carotid IMT did not show any association with nutritional indices; but positively correlated with serum IL-6 (P = 0.037), CRP (P = 0.012), and iPTH (P = 0.009), and independently associated with only iPTH (P = 0.018). Children on dialysis are at an increased risk of malnutrition, inflammation, and vascular disease. Although each of these three conditions exists, there is no interaction among them all. We postulate that the malnutrition-inflammation-atherosclerosis (MIA) complex might not exist in pediatric dialysis patients.

  13. The gut microbiome in atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  14. Diagnosing extracranial atherosclerotic diseases with spiral CT

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  15. Peripheral vascular disease is associated with reduced glycosuria in newly diagnosed type 2 diabetic patients

    DEFF Research Database (Denmark)

    Olivarius, Niels de Fine; Holstein-Rathlou, N H; Siersma, V

    2004-01-01

    was 65.2 years. Urinary glucose concentration (UGC) was determined quantitatively in a freshly voided morning urine specimen. RESULTS: The over-all prevalence of peripheral vascular disease (PVD) was 16.5%. Bivariately, high values of UGC were associated with low prevalence of PVD (p...). The predictive value of PVD--together with HbA1c, glomerular filtration rate (GFR) and 10 other possible predictors--was confirmed in a logistic regression analysis with glycosuria (Y/N) as outcome variable (p=0.0004). CONCLUSION: Surprisingly, type 2 diabetic patients with PVD tend not to have glycosuria...... as compared to patients without PVD. PVD may be indicative of generalized atherosclerotic lesions in the major vessels, including the renal arteries. This could lead to a lowering of GFR and thereby of the amount of glucose filtered. Assuming no, or only a minor direct effect of PVD on tubular function...

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

    Directory of Open Access Journals (Sweden)

    Mukaisho K

    2012-05-01

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

  17. Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-γ: Therapeutic Implications for Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Florence Gizard

    2008-01-01

    Full Text Available Proliferation of vascular smooth muscle cells (SMCs is a critical process for the development of atherosclerosis and complications of procedures used to treat atherosclerotic diseases, including postangioplasty restenosis, vein graft failure, and transplant vasculopathy. Peroxisome proliferator-activated receptor (PPAR γ is a member of the nuclear hormone receptor superfamily and the molecular target for the thiazolidinediones (TZD, used clinically to treat insulin resistance in patients with type 2 diabetes. In addition to their efficacy to improve insulin sensitivity, TZD exert a broad spectrum of pleiotropic beneficial effects on vascular gene expression programs. In SMCs, PPARγ is prominently upregulated during neointima formation and suppresses the proliferative response to injury of the arterial wall. Among the molecular target genes regulated by PPARγ in SMCs are genes encoding proteins involved in the regulation of cell-cycle progression, cellular senescence, and apoptosis. This inhibition of SMC proliferation is likely to contribute to the prevention of atherosclerosis and postangioplasty restenosis observed in animal models and proof-of-concept clinical studies. This review will summarize the transcriptional target genes regulated by PPARγ in SMCs and outline the therapeutic implications of PPARγ activation for the treatment and prevention of atherosclerosis and its complications.

  18. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults.

    Science.gov (United States)

    Pfeifer, M; Verhovec, R; Zizek, B; Prezelj, J; Poredos, P; Clayton, R N

    1999-02-01

    functional atherosclerotic changes in major arteries and, if maintained, may reduce vascular morbidity and mortality. GH seems to act via IGF-I, which is known to have important effects on endothelial cell function.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

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    Veronika A. Myasoedova

    2016-08-01

    Full Text Available The risk of cardiovascular disease and atherosclerosis progression is significantly increased after menopause, probably due to the decrease of estrogen levels. The use of hormone replacement therapy (HRT for prevention of cardiovascular disease in older postmenopausal failed to meet expectations. Phytoestrogens may induce some improvements in climacteric symptoms, but their effect on the progression of atherosclerosis remains unclear. The reduction of cholesterol accumulation at the cellular level should lead to inhibition of the atherosclerotic process in the arterial wall. The inhibition of intracellular lipid deposition with isoflavonoids was suggested as the effective way for the prevention of plaque formation in the arterial wall. The aim of this double-blind, placebo-controlled clinical study was to investigate the effect of an isoflavonoid-rich herbal preparation on atherosclerosis progression in postmenopausal women free of overt cardiovascular disease. One hundred fifty-seven healthy postmenopausal women (age 65 ± 6 were randomized to a 500 mg isoflavonoid-rich herbal preparation containing tannins from grape seeds, green tea leaves, hop cone powder, and garlic powder, or placebo. Conventional cardiovascular risk factors and intima-media thickness of common carotid arteries (cIMT were evaluated at the baseline and after 12 months of treatment. After 12-months follow-up, total cholesterol decreased by 6.3% in isoflavonoid-rich herbal preparation recipients (p = 0.011 and by 5.2% in placebo recipients (p = 0.020; low density lipoprotein (LDL cholesterol decreased by 7.6% in isoflavonoid-rich herbal preparation recipients (p = 0.040 and by 5.2% in placebo recipients (non-significant, NS; high density lipoprotein (HDL cholesterol decreased by 3.4% in isoflavonoid-rich herbal preparation recipients (NS and by 4.5% in placebo recipients (p = 0.038; triglycerides decreased by 6.0% in isoflavonoid-rich herbal preparation recipients (NS and by

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

    Science.gov (United States)

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

    2008-10-01

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

  2. Surgical treatment of penetrating atherosclerotic ulcer of the descending aorta

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    Kovačević Pavle

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

    Several studies have attempted to characterize intracranial atherosclerotic plaques by using MR imaging sequences. However, dedicated validation of these sequences with histology has not yet been performed. The current study assessed the ability of ultra-high-resolution 7T MR imaging sequences with

  4. Optical coherence tomography in quantifying the permeation of human plasma lipoproteins in vascular tissues

    Science.gov (United States)

    Ghosn, M. G.; Mashiatulla, M.; Tuchin, V. V.; Morrisett, J. D.; Larin, K. V.

    2012-03-01

    Atherosclerosis is the most common underlying cause of vascular disease, occurring in multiple arterial beds including the carotid, coronary, and femoral arteries. Atherosclerosis is an inflammatory process occurring in arterial tissue, involving the subintimal accumulation of low-density lipoproteins (LDL). Little is known about the rates at which these accumulations occur. Measurements of the permeability rate of LDL, and other lipoproteins such as high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL), could help gain a better understanding of the mechanisms involved in the development of atherosclerotic lesions. The permeation of VLDL, LDL, HDL, and glucose was monitored and quantified in normal and diseased human carotid endarterectomy tissues at 20°C and 37°C using optical coherence tomography (OCT). The rates for LDL permeation through normal tissue at 20°C was (3.16 +/- 0.37) × 10-5 cm/sec and at 37°C was (4.77 +/- 0.48) × 10-5 cm/sec, significantly greater (plipoproteins.

  5. Ophthalmic masquerades of the atherosclerotic carotids

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    Anupriya Arthur

    2014-01-01

    Full Text Available Patients with carotid atherosclerosis can present with ophthalmic symptoms. These symptoms and signs can be due to retinal emboli, hypoperfusion of the retina and choroid, opening up of collateral channels, or chronic hypoperfusion of the globe (ocular ischemic syndrome. These pathological mechanisms can produce many interesting signs and a careful history can bring out important past symptoms pointing toward the carotid as the source of the patient′s presenting symptom. Such patients are at high risk for an ischemic stroke, especially in the subsequent few days following their first acute symptom. It is important for clinicians to be familiar with these ophthalmic symptoms and signs caused by carotid atherosclerosis for making an early diagnosis and to take appropriate measures to prevent a stroke. This review elaborates the clinical features, importance, and implications of various ophthalmic symptoms and signs resulting from atherosclerotic carotid artery disease.

  6. A survey of current practice of vascular surgeons in venous disease management.

    Science.gov (United States)

    Bush, Ruth L; Gloviczki, Peter

    2013-01-01

    Acute venous thromboembolism and chronic venous diseases are common conditions that affect a large proportion of the United States population. The diagnosis of venous disease has improved, and the treatment options have rapidly evolved over the past decade. To date, it is unclear to what extent vascular surgeons have become involved in the modern management of venous disorders. This survey was undertaken to explore the current interest and practice of vascular surgeons in the contemporary care of venous disease. A survey was administered via a web-based platform to active and candidate members of the Society for Vascular Surgery (SVS). The survey included 30 questions investigating the characteristics of venous surgeons and scope of venous practice. Open-ended questions were also included for commentary. A total of 1879 surveys were sent to SVS members nationwide, and 385 members participated (response rate of 20.5%). The participants were mostly men (89.6%) with 37.7% practicing in an academic setting and 59.2% in private practice. The respondents treated superficial veins (92.9%) and deep veins (85.8%) in clinical practice, with 89.9% having their own vascular laboratory. A wide spectrum of interventions for superficial (91.9%), deep (85.8%), and perforator veins (52.7% endovenous, 19.4% subfascial endoscopic perforator surgery) are being performed by respondents. Only 26.2% had learned endovenous thermal ablation in their training program; however, over 96% of those performing venous interventions utilized this technique. Overall, the majority (85.5%) devoted 50% or less of practice to venous disorders. Respondents indicated that limitations to expansion of vein practices mainly involved challenges with third party payers, local competition, and existing large volumes of arterial interventions needing to be performed. Despite the widespread incorporation of venous disease into current vascular practices, 66.1% are not members of the American Venous Forum (AVF

  7. Snoring and atherosclerotic manifestations in a 70-year-old population

    DEFF Research Database (Denmark)

    Jennum, P; Schultz-Larsen, K; Christensen, N J

    1996-01-01

    the issue we examined the association between self-assessed snoring and the relation to atherosclerotic manifestations. 804 70-year-old males and females were classified according to snoring habits. Alcohol and tobacco consumption, blood pressure, body mass index, social group, plasma lipids (triglycerides......, cholesterol, high density lipoprotein), fasting blood glucose, glucose tolerance test, plasma epinephrine and norepinephrine were determined. Presence of angina pectoris, claudication intermittens, use of nitroglycerine were questioned, a resting ECG and a distal arterial pressure by use of doppler technique...

  8. Evaluation of the early enhancement of coronary atherosclerotic plaque by contrast-enhanced MR angiography

    Energy Technology Data Exchange (ETDEWEB)

    Li Tao [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhao Xihai [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Liu Xin [Paul C. Lauterbur Biomedical Imaging Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen 518067 (China); Gao Jianhua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Zhao Shaohong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Li Xin; Zhou Weihua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Cai Zulong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhang Weiguo [Cardiovascular and Neurological Consulting Institute, 6771 San Fernando, Irving, TX 75039 (United States); Yang Li, E-mail: Yangli301@yahoo.com [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China)

    2011-10-15

    Purpose: To evaluate the early enhancement of coronary atherosclerotic plaque using contrast-enhanced MR angiography (CE-MRA) and investigate the association between unstable angina pectoris (UAP) and early enhancement of the plaque. Methods: Forty-one patients presenting with angina pectoris and demonstrating single-vessel disease with non-calcified plaque and significant coronary stenosis ({>=}50%) on CTA were consecutively recruited for coronary CE-MRA. Contrast-to-noise ratio of the culprit plaque guided by CTA was measured on a cross-sectional multi-planar reconstruction image of the plaque on both pre- and post-CE-MRA. A 50% increasing of CNR was defined as plaque enhancement. The association between early enhancement of the plaques and UAP was analyzed. Results: Thirty-seven non-calcified plaques with significant coronary stenosis were detected in the 37 patients on MRA. 4 subjects were excluded because coronary atherosclerotic plaques were inadequate for identification on MRA. Of the 37 patients, 18 patients had UAP and other 19 patients presented stable angina pectoris (SAP). Of the 37 plaques on CE-MRA, 13 and 24 plaques presented early enhancement and no enhancement, respectively. Of the 13 early-enhanced plaques, 11 (85%) and 2 (15%) were found in the patients with UAP and SAP, respectively (p < 0.01). Of the 37 patients, 11 (61%) with UAP and 2 (11%) with SAP had early-enhanced plaques, respectively (p < 0.01). Conclusion: CE-MRA allows detection of early enhancement of coronary atherosclerotic plaque. The early enhancement is common in unstable angina and could be a sign of vulnerability.

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

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    Meng Zhang

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

  10. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice.

    Science.gov (United States)

    Muñoz-García, Begoña; Moreno, Juan Antonio; López-Franco, Oscar; Sanz, Ana Belén; Martín-Ventura, José Luis; Blanco, Julia; Jakubowski, Aniela; Burkly, Linda C; Ortiz, Alberto; Egido, Jesús; Blanco-Colio, Luis Miguel

    2009-12-01

    Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice. ApoE(-/-) mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 microg/kg/d), anti-TWEAK neutralizing mAb (1000 microg/kg/d), TWEAK plus anti-TWEAK antibody (10 microg TWEAK +1000 microg anti-TWEAK/kg/d), or nonspecific IgG (1000 microg/kg/d) daily for 9 days. In ApoE(-/-) mice, exogenous TWEAK administration in ApoE(-/-) mice induced activation of NF-kappaB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE(-/-) mice with an anti-TWEAK blocking mAb decreased NF-kappaB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion. Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid-rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with

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

    Science.gov (United States)

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

    2017-01-01

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

  12. Gait and Equilibrium in Subcortical Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Rita Moretti

    2011-01-01

    Full Text Available Subcortical vascular dementia is a clinical entity, widespread, even challenging to diagnose and correctly treat. Patients with this diagnosis are old, frail, often with concomitant pathologies, and therefore, with many drugs in therapy. We tried to diagnose and follow up for three years more than 600 patients. Study subjects were men and women, not bedridden, aged 68–94 years, outpatients, recruited from June, 1st 2007 to June, 1st 2010. We examined them clinically, neurologically, with specific consideration on drug therapies. Our aim has been to define gait and imbalance problem, if eventually coexistent with the pathology of white matter and/or with the worsening of the deterioration. Drug intake interference has been detected and considered.

  13. Major Vascular Neurocognitive Disorder: A Reappraisal to Vascular Dementia

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    Emre Kumral

    2017-03-01

    Full Text Available Major vascular neurocognitive disorder (NCD is the second leading form of dementia after Alzheimer’s disease, accounting for 17-20% of all dementias. Vascular NCD is a progressive disease caused by reduced cerebral blood flow related to multiple large volume or lacunar infarcts that induce a sudden onset and stepwise decline in cognitive abilities. Despite its prevalence and clinical importance, there is still controversy in the terminology of vascular NCD. Only after the release of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5 (2013 did the American Psychiatric Association define vascular dementia as “major vascular NCD”. This review includes an overview of risk factors, pathophysiology, types, diagnostic and clinical features of major vascular NCD, and current treatment options of vascular NCD regarding to DSM-5 criteria

  14. The gut microbiome in atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

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

    2017-01-01

    The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals...... with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular......), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform...

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  17. Serum-Sphingosine-1-Phosphate Concentrations Are Inversely Associated with Atherosclerotic Diseases in Humans.

    Directory of Open Access Journals (Sweden)

    Irina Soltau

    Full Text Available Atherosclerotic changes of arteries are the leading cause for deaths in cardiovascular disease and greatly impair patient's quality of life. Sphingosine-1-phosphate (S1P is a signaling sphingolipid that regulates potentially pro-as well as anti-atherogenic processes. Here, we investigate whether serum-S1P concentrations are associated with peripheral artery disease (PAD and carotid stenosis (CS.Serum was sampled from blood donors (controls, N = 174 and from atherosclerotic patients (N = 132 who presented to the hospital with either clinically relevant PAD (N = 102 or CS (N = 30. From all subjects, serum-S1P was measured by mass spectrometry and blood parameters were determined by routine laboratory assays. When compared to controls, atherosclerotic patients before invasive treatment to restore blood flow showed significantly lower serum-S1P levels. This difference cannot be explained by risk factors for atherosclerosis (old age, male gender, hypertension, hypercholesteremia, obesity, diabetes or smoking or comorbidities (Chronic obstructive pulmonary disease, kidney insufficiency or arrhythmia. Receiver operating characteristic curves suggest that S1P has more power to indicate atherosclerosis (PAD and CS than high density lipoprotein-cholesterol (HDL-C. In 35 patients, serum-S1P was measured again between one and six months after treatment. In this group, serum-S1P concentrations rose after treatment independent of whether patients had PAD or CS, or whether they underwent open or endovascular surgery. Post-treatment S1P levels were highly associated to platelet numbers measured pre-treatment.Our study shows that PAD and CS in humans is associated with decreased serum-S1P concentrations and that S1P may possess higher accuracy to indicate these diseases than HDL-C.

  18. Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

    Directory of Open Access Journals (Sweden)

    Patrik Htun

    Full Text Available Since patients with phenylketonuria (PKU have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT and ß-stiffness index] and platelet activation.In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation. CIMT was measured bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of CIMTleft and CIMTright.Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group.Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients.

  19. Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

    Science.gov (United States)

    Htun, Patrik; Nee, Jens; Ploeckinger, Ursula; Eder, Klaus; Geisler, Tobias; Gawaz, Meinrad; Bocksch, Wolfgang; Fateh-Moghadam, Suzanne

    2015-01-01

    Since patients with phenylketonuria (PKU) have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT) and ß-stiffness index] and platelet activation. In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation). CIMT was measured bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of CIMTleft and CIMTright. Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group. Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients.

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

    Science.gov (United States)

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

    2011-12-21

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

  1. NF-κB inhibitors that prevent foam cell formation and atherosclerotic plaque accumulation.

    Science.gov (United States)

    Plotkin, Jesse D; Elias, Michael G; Dellinger, Anthony L; Kepley, Christopher L

    2017-08-01

    The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbol myristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology.Lipoprotein-induced generation of TNF-α, C5a-induced MC activation, ICAM-1 driven adhesion, and CD36 expression were significantly inhibited in FD treated cells compared to non-treated cells. Inhibition appeared to be mediated through the NF-κB pathway as FD reduced expression of NF-κB and atherosclerosis-associated genes. Compared to controls, FD dramatically inhibited plaque formation in arteries of apolipoprotein E null mice. Thus, FD may be an unrecognized therapy to prevent atherosclerotic lesions via inhibition of foam cell formation and MC stabilization. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Fagerberg, Björn; Barregard, Lars; Sallsten, Gerd; Forsgard, Niklas; Östling, Gerd; Persson, Margaretha; Borné, Yan

    2015-01-01

    Background: Epidemiological studies indicate that cadmium exposure through diet and smoking is associated with increased risk of cardiovascular disease. There are few data on the relationship between cadmium and plaques, the hallmark of underlying atherosclerotic disease. Objectives: To examine the association between exposure to cadmium and the prevalence and size of atherosclerotic plaques in the carotid artery. Methods: A population sample of 4639 Swedish middle-aged women and men was examined in 1991–1994. Carotid plaque was determined by B-mode ultrasound. Cadmium in blood was analyzed by inductively coupled plasma mass spectrometry. Results: Comparing quartile 4 with quartile 1 of blood cadmium, the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6–2.2) after adjustment for sex and, age; 1.4 (1.1–1.8) after additional adjustment for smoking status; 1.4 (1.1–1.7) after the addition of education level and life style factors; 1.3 (1.03–1.8) after additional adjustment for risk factors and predictors of cardiovascular disease. No effect modification by sex was found in the cadmium-related prevalence of plaques. Similarly, ORs for the prevalence of small and large plaques were after full adjustment 1.4 (1.0–2.1) and 1.4 (0.9–2.0), respectively. The subgroup of never smokers showed no association between cadmium and atherosclerotic plaques. Conclusions: These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans. The role of smoking remains unclear. It may both cause residual confounding and be a source of pro-atherogenic cadmium exposure. - Highlights: • Blood cadmium level is associated with atherosclerotic plaques in the carotid artery. • The results extend previous knowledge of cadmium exposure and clinical events. • The role of smoking remains unclear

  3. 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.

  4. Targeting Tumor Necrosis Factor-α with Adalimumab: Effects on Endothelial Activation and Monocyte Adhesion.

    Directory of Open Access Journals (Sweden)

    Raghav Oberoi

    Full Text Available It is well known that atherosclerotic inflammatory vascular disease is critically driven by oxidized lipids and cytokines. In this regard, tumor necrosis factor (TNF-α is known as a crucial mediator of early pro-atherosclerotic events. Epidemiologic data suggest that blockade of TNF-α has beneficial effects on vascular outcomes in patients with rheumatoid arthritis, however, detailed mechanistic studies are still lacking. This study aims to elucidate effects of TNF-α blockade by adalimumab-which is approved for several inflammatory disorders-on endothelial activation and monocyte adhesion under pro-atherosclerotic conditions.Phorbol myristate acetate (PMA differentiated THP-1 macrophages were stimulated with oxidized low density lipoprotein and subsequent analysis of this conditioned media (oxLDL CM revealed a strong release of TNF-α. The TNF-α rich supernatant led to activation of human umbilical vein endothelial cells (HUVEC as shown by enhanced expression of major adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1, intercellular adhesion molecule-1 (ICAM-1 and E-selectin which was suppressed by the TNF-α inhibitor adalimumab. Accordingly, adalimumab effectively prevented THP-1 monocyte adhesion to endothelial cells under static as well as under flow conditions. Furthermore, adalimumab suppressed endothelial leakage as shown by Evan's blue diffusion across a confluent endothelial monolayer. Of note, after intraperitoneal injection we detected abundant deposition of fluorophore-labelled adalimumab in atherosclerotic plaques of hypercholesterolemic mice.Our results show that adalimumab prevents major inflammatory effects of TNF-α on endothelial activation, endothelial monocyte adhesion, endothelial leakage and therefore extends the therapeutic options of adalimumab to limit vascular inflammation.

  5. Endovascular revascularization for aortoiliac atherosclerotic disease

    Directory of Open Access Journals (Sweden)

    Aggarwal V

    2016-03-01

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

  6. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    Science.gov (United States)

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  7. The effect of aging on atherosclerotic plaque inflammation and molecular calcification: A PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Simonsen, Jane Angel

    Aim: Aging is an important independent risk factor for the inception and maturation of atherosclerotic plaques. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and molecular calcification. Methods: Thirteen healthy volunteers without traditional......SUV) [Mean SUVAORTA - Mean SUVBLOOD POOL]. Furthermore, the average maximum 18F-NaF cSUV was determined in the coronary arteries. Calculating regression and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18F-FDG avidity. A second order...... polynomial regression established that aging is a strong predictor of the degree of aortic plaque inflammation (R2 = 0.71, F statistic = 11.98, P = 0.002). A linear relationship was observed between aging and molecular calcification. Linear regression established that aging is a predictor of both the degree...

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

    Science.gov (United States)

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

    2016-09-09

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

  9. Protocatechuic aldehyde inhibits migration and proliferation of vascular smooth muscle cells and intravascular thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Chang Yoon [The Hotchkiss School, Lakeville, CT (United States); Endocrinology, Brain Korea 21 Project for Medical Science, Institute of Endocrine Research, and Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University College of Medicine, Seoul (Korea, Republic of); Ku, Cheol Ryong [Endocrinology, Brain Korea 21 Project for Medical Science, Institute of Endocrine Research, and Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Yoon Hee, E-mail: wooriminji@gmail.com [Endocrinology, Brain Korea 21 Project for Medical Science, Institute of Endocrine Research, and Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Eun Jig, E-mail: ejlee423@yuhs.ac [Endocrinology, Brain Korea 21 Project for Medical Science, Institute of Endocrine Research, and Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University College of Medicine, Seoul (Korea, Republic of); Endocrinology, Northwestern University Feinberg School of Medicine, Chicago, IL (United States)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Protocatechuic aldehyde (PCA) inhibits ROS production in VSMCs. Black-Right-Pointing-Pointer PCA inhibits proliferation and migration in PDGF-induced VSMCs. Black-Right-Pointing-Pointer PCA has anti-platelet effects in ex vivo rat whole blood. Black-Right-Pointing-Pointer We report the potential therapeutic role of PCA in atherosclerosis. -- Abstract: The migration and proliferation of vascular smooth muscle cells (VSMCs) and formation of intravascular thrombosis play crucial roles in the development of atherosclerotic lesions. This study examined the effects of protocatechuic aldehyde (PCA), a compound isolated from the aqueous extract of the root of Salvia miltiorrhiza, an herb used in traditional Chinese medicine to treat a variety of vascular diseases, on the migration and proliferation of VSMCs and platelets due to platelet-derived growth factor (PDGF). DNA 5-bromo-2 Prime -deoxy-uridine (BrdU) incorporation and wound-healing assays indicated that PCA significantly attenuated PDGF-induced proliferation and migration of VSMCs at a pharmacologically relevant concentration (100 {mu}M). On a molecular level, we observed down-regulation of the phosphatidylinositol 3-kinase (PI3K)/Akt and the mitogen-activated protein kinase (MAPK) pathways, both of which regulate key enzymes associated with migration and proliferation. We also found that PCA induced S-phase arrest of the VSMC cell cycle and suppressed cyclin D2 expression. In addition, PCA inhibited PDGF-BB-stimulated reactive oxygen species production in VSMCs, indicating that PCA's antioxidant properties may contribute to its suppression of PDGF-induced migration and proliferation in VSMCs. Finally, PCA exhibited an anti-thrombotic effect related to its inhibition of platelet aggregation, confirmed with an aggregometer. Together, these findings suggest a potential therapeutic role of PCA in the treatment of atherosclerosis and angioplasty-induced vascular restenosis.

  10. Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

    Science.gov (United States)

    Uryga, Anna K; Bennett, Martin R

    2016-04-15

    Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

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

    NARCIS (Netherlands)

    Keller, Tymen T.; van der Meer, Jelger J.; Teeling, Peter; van der Sluijs, Koen; Idu, Mirza M.; Rimmelzwaan, Guus F.; Levi, Marcel; van der Wal, Allard C.; de Boer, Onno J.

    2008-01-01

    Background and Purpose-Evidence is accumulating that infection with influenza A virus contributes to atherothrombotic disease. Vaccination against influenza decreases the risk of atherosclerotic syndromes, indicating that inflammatory mechanisms may be involved. We tested the hypothesis that

  12. Puzzles in modern biology. IV. Neurodegeneration, localized origin and widespread decay [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Steven A. Frank

    2016-10-01

    Full Text Available The motor neuron disease amyotrophic lateral sclerosis (ALS typically begins with localized muscle weakness. Progressive, widespread paralysis often follows over a few years. Does the disease begin with local changes in a small piece of neural tissue and then spread? Or does neural decay happen independently across diverse spatial locations? The distinction matters, because local initiation may arise by local changes in a tissue microenvironment, by somatic mutation, or by various epigenetic or regulatory fluctuations in a few cells. A local trigger must be coupled with a mechanism for spread. By contrast, independent decay across spatial locations cannot begin by a local change, but must depend on some global predisposition or spatially distributed change that leads to approximately synchronous decay. This article outlines the conceptual frame by which one contrasts local triggers and spread versus parallel spatially distributed decay. Various neurodegenerative diseases differ in their mechanistic details, but all can usefully be understood as falling along a continuum of interacting local and global processes. Cancer provides an example of disease progression by local triggers and spatial spread, setting a conceptual basis for clarifying puzzles in neurodegeneration. Heart disease also has crucial interactions between global processes, such as circulating lipid levels, and local processes in the development of atherosclerotic plaques. The distinction between local and global processes helps to understand these various age-related diseases.

  13. Original Article

    African Journals Online (AJOL)

    Abstract. Introduction: Fetuin-A, a systemic calcification inhibitor, has been negatively related to vascular calcification. (VC) and cardiovascular mortality. In this study we investigated the association between fetuin-A levels and atherosclerotic vascular complications in systemic lupus erythematosus (SLE) patients with and ...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Vascular adrenergic receptor responses in skeletal muscle in myotonic dystrophy

    International Nuclear Information System (INIS)

    Mechler, F.; Mastaglia, F.L.

    1981-01-01

    The pharmacological responses of vascular adrenergic receptors to intravenously administered epinephrine, phentolamine, and propranolol were assessed by measuring muscle blood flow (MBF) changes in the tibialis anterior muscle using the xenon 133 clearance technique and were compared in 8 normal subjects and 11 patients with myotonic dystrophy. In cases with advanced involvement of the muscle, the resting MBF was reduced and was not significantly altered by epinephrine before or after alpha- or beta-receptor blockade. In patients in whom the tibialis anterior muscle was normal or only minimally affected clinically, a paradoxical reduction in the epinephrine-induced increase in MBF was found after alpha blockade by phentolamine, and the epinephrine-induced MBF increase was not completely blocked by propranolol as in the normal subjects. These findings point to functional alteration in the properties of vascular adrenergic receptors in muscle in myotonic dystrophy. While this may be another manifestation of a widespread cell membrane defect in the disease, the possibility that the changes are secondary to the myotonic state cannot be excluded

  16. Enhanced Biosensor Platforms for Detecting the Atherosclerotic Biomarker VCAM1 Based on Bioconjugation with Uniformly Oriented VCAM1-Targeting Nanobodies

    Directory of Open Access Journals (Sweden)

    Duy Tien Ta

    2016-07-01

    Full Text Available Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1, an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL. Conjugation of this nanobody to azidified silicon wafers and Biacore™ C1 sensor chips is achieved via Copper(I-catalyzed azide-alkyne cycloaddition (CuAAC “click” chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR, respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets—a must for the development of advanced miniaturized, multi-biomarker biosensor platforms.

  17. Calcified carotid atherosclerotic plaques on digital panoramic radiographs in patients with Type II diabetes mellitus: A case control study

    Directory of Open Access Journals (Sweden)

    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.

  18. Diabetes mellitus and ischemic diseases: molecular mechanisms of vascular repair dysfunction.

    Science.gov (United States)

    Howangyin, Kiave Yune; Silvestre, Jean-Sébastien

    2014-06-01

    In patients with diabetes mellitus, the ability of ischemic tissue to synchronize the molecular and cellular events leading to restoration of tissue perfusion in response to the atherosclerotic occlusion of a patent artery is markedly impaired. As a consequence, adverse tissue remodeling and the extent of ischemic injury are intensified, leading to increased morbidity and mortality. Growing evidence from preclinical and clinical studies has implicated alterations in hypoxia-inducible factor 1 levels in the abrogation of proangiogenic pathways, including vascular endothelial growth factor A/phosphoinositide 3' kinase/AKT/endothelial nitric oxide synthase and in the activation of antiangiogenic signals characterized by accumulation of advanced glycation end products, reactive oxygen species overproduction, and endoplasmic reticulum stress. In addition, the diabetic milieu shows a switch toward proinflammatory antiregenerative pathways. Finally, the mobilization, subsequent recruitment, and the proangiogenic potential of the different subsets of angiogenesis-promoting bone marrow-derived cells are markedly impaired in the diabetic environment. In this review, we will give an overview of the current understanding on the signaling molecules contributing to the diabetes mellitus-induced impairment of postischemic revascularization mainly in the setting of myocardial infarction or critical limb ischemia. © 2014 American Heart Association, Inc.

  19. 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.

  20. Non-invasive vascular imaging: assessing tumour vascularity

    International Nuclear Information System (INIS)

    Delorme, S.; Knopp, M.V.

    1998-01-01

    Non-invasive assessment of vascularity is a new diagnostic approach to characterise tumours. Vascular assessment is based on the pathophysiology of tumour angiogenesis and its diagnostic implications for tumour biology, prognosis and therapy response. Two current techniques investigating vascular features in addition to morphology are Doppler ultrasonography and contrast-enhanced MRI. Diagnostic differentiation has been shown to be possible with Doppler, and a high degree of observed vascularity could be linked to an aggressive course of the disease. Dynamic MRI using gadolinium chelates is already used clinically to detect and differentiate tumours. The histological correlation shows that capillary permeability is increased in malignant tumours and is the best criterion for differentiation from benign processes. Permeability and perfusion factors seem to be more diagnostic than overall vessel density. New clinical applications are currently being established for therapy monitoring. Further instrumental developments will bring harmonic imaging in Doppler, and faster imaging techniques, higher spatial resolution and novel pharmacokinetic concepts in MRI. Upcoming contrast agents for both Doppler and MRI will further improve estimation of intratumoural blood volume and vascular permeability. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Zeki Dostbil

    2010-09-01

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

  2. 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

  3. Evaluation of radiotracers for the detection of atherosclerotic vulnerable plaque and myocardial angiogenesis

    International Nuclear Information System (INIS)

    Dimastromatteo, Julien

    2010-01-01

    Cardiovascular diseases are the leading cause of mortality worldwide. Coronary events are mainly caused by coronary plaque rupture or erosion. However, at present, there is no noninvasive tool available for the detection of vulnerable plaques. The first part of thesis is about evaluation of new radiotracers for the detection of atherosclerotic vulnerable plaques. 99m Tc-B2702p, 20 derivatives, 99m Tc-VP and 99m Tc-VINP28 were evaluated in an experimental model of atherosclerosis (ApoE-/- mice with left carotid artery ligation). 99m Tc- B2702p1 is a potentially useful radiotracer for the in vivo molecular imaging of VCAM-1 expression in atherosclerotic plaques. Myocardial angiogenesis is an important post infarction phenomenon. Angiogenic therapy improves experimentally cardiac parameters. However, clinical trials using the same therapy are more controversial. At present, clinical imaging tools don't allow us to assess angiogenesis therapy. The second part of thesis is about validation of 99m Tc-RAFT-RGD in the detection of myocardial angiogenesis. 99m Tc-RAFT-RGD allow us to perform noninvasive molecular imaging of myocardial angiogenesis in an experimental model. (author)

  4. Influence of ghrelin gene polymorphisms on hypertension and atherosclerotic disease.

    Science.gov (United States)

    Berthold, Heiner K; Giannakidou, Eleni; Krone, Wilhelm; Trégouët, David-Alexandre; Gouni-Berthold, Ioanna

    2010-02-01

    Ghrelin is involved in several metabolic and cardiovascular processes. Recent evidence suggests its involvement in blood pressure regulation and hypertension. The aim of the study was to determine associations of single-nucleotide polymorphisms (SNPs) and haplotypes of the ghrelin gene (GHRL) with hypertension and atherosclerotic disease. Six GHRL SNPs (rs27647, rs26802, rs34911341, rs696217, rs4684677 and a -473G/A (with no assigned rsID)) were investigated in a sample of 1143 hypertensive subjects and 1489 controls of Caucasian origin. Both single-locus and haplotype association analyses were performed. In single-locus analyses, only the non-synonymous rs34911341 was associated with hypertension (odds ratio (OR)=1.95 (95% confidence interval (CI): 1.26-3.02), P=0.003). Six common haplotypes with frequency >1% were inferred from the studied GHRL SNPs, and their frequency distribution was significantly different between hypertensive subjects and controls (chi(2)=12.96 with 5 d.f. (degree of freedom), P=0.024). The effect of rs26802 was found to be significantly (P=0.017) modulated by other GHRL SNPs, as its C allele conferred either an increased risk (OR=1.30 (1.08-1.57), P=0.005) or a decreased risk (OR=0.50 (0.23-1.06), P=0.07) of hypertension according to the two different haplotypes on which it can be found. No association of GHRL SNPs or haplotypes with atherosclerotic disease was observed. In conclusion, we observed statistical evidence for association between GHRL SNPs and risk of hypertension.

  5. Widespread pain: is an improved classification possible?

    Science.gov (United States)

    MacFarlane, G J; Croft, P R; Schollum, J; Silman, A J

    1996-09-01

    The classification of widespread pain, proposed by the American College of Rheumatology (ACR) for use in the clinic as a screen for fibromyalgia, as described, does not require truly widespread pain. Studies considering the epidemiology of widespread pain per se may therefore require a definition with greater face validity, which might also show enhanced associations with other physical and psychological measures. We aimed to develop a more coherent definition of widespread pain for use in epidemiological studies and to compare performance in identifying individuals with significant morbidity. A group of 172 subjects who had participated in a community based study on the occurrence of pain were identified and categorized by their pain experience as indicated on line drawings of the body according to ACR definition and to a new, more stringent definition that required the presence of more diffuse limb pain. A number of other clinical and psychological measures were recorded for these individuals and the association between their pain status measures and these other variables was assessed and compared. Persons satisfying the newly proposed definition for chronic widespread pain, in comparison with those who satisfied only the present ACR definition, had a significantly higher score on the General Health Questionnaire [median difference (MD) 7.95% CI 1.13], a higher score on the Health and Fatigue Questionnaire (MD 10.95% CI 0.15), and greater problems with sleep (sleep problem score MD 4.95% CI 0.9). Those satisfying the new definition also had a greater number of tender points on examination (MD 3.95% CI -1.7). The morbidity of those satisfying only the present ACR definition was closer to persons who had regional pain. A redefinition of widespread pain has produced a group of subjects whose pain is (a) likely to be more "widespread" and (b) is associated more strongly with factors such as psychological disturbance, fatigue, sleep problems, and tender points, and

  6. Personality disparity in chronic regional and widespread pain.

    Science.gov (United States)

    Chang, Mei-Chung; Chen, Po-Fei; Lung, For-Wey

    2017-08-01

    Chronic pain has high comorbidity with psychiatric disorders, therefore, better understanding of the relationship between chronic pain and mental illness is needed. This study aimed to investigate the pathway relationships among parental attachment, personality characteristics, alexithymic trait and mental health in patients with chronic widespread pain, those with chronic regional pain, and controls. Two hundred and thirty participants were recruited. The parental Bonding Inventory, Eysenck Personality Inventory (EPI), 20-item Toronto Alexithymia Scale (TAS-20), Chinese Health Questionnaire, and Short-Form 36 were filled out. The pathway relationships revealed that patients of mothers who were more protective were more neurotic, had more difficulty identifying feelings (DIF), worse mental health, and a higher association with chronic widespread pain. No differences were found between patients with chronic regional pain and the controls. The predisposing factors for chronic widespread pain, when compared with chronic regional pain, may be more closely related to psychiatric disorders. The pathways to chronic regional pain and chronic widespread pain differ, with neuroticism and the alexithymic DIF trait being the main factors defining chronic widespread pain. Therefore, besides therapies targeting pain symptoms, psychiatric consultation, medication and psychotherapy are also recommended for those with chronic widespread pain to alleviate their mental health conditions. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Influence of folic acid, pyridoxal phosphate and cobalamin on plasma homocyst(e)ine levels and the susceptibility of low-density lipoprotein to ex-vivo oxidation.

    Science.gov (United States)

    Weiss, N; Feussner, A; Hailer, S; Spengel, F A; Keller, C; Wolfram, G

    1999-10-15

    Mild hyperhomocyst(e)inaemia is a risk factor for atherosclerotic vascular disease. In-vitro studies have shown that autooxidation of homocyst(e)ine is accompanied by the generation of oxygen radicals. This may lead to oxidative modification of low-density lipoproteins (LDL) and promote atherosclerotic vascular lesions. In male patients with peripheral arterial occlusive disease we determined fasting and post methionine load homocyst(e)ine levels by high performance liquid chromatography and the susceptibility of their LDL particles to ex-vivo oxidation by continously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed of total diene production) of LDL from patients with normal or mildly elevated homocyst(e)ine levels did not differ significantly. Folic acid, pyridoxal phosphate and cobalamin supplementation significantly decreased plasma homocyst(e)ine levels in hyperhomocyst(e)inaemic patients. This went along with a significant decrease in the extent of LDL oxidation and additionally increased HDL-cholesterol levels. The clinical relevance of these findings for the long-term course of atherosclerotic vascular disorders has to be determined by intervention studies.

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

    Science.gov (United States)

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

    2011-01-01

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

  9. Mathematical and numerical modeling of early atherosclerotic lesions***

    Directory of Open Access Journals (Sweden)

    Raoult Annie

    2010-12-01

    Full Text Available This article is devoted to the construction of a mathematical model describing the early formation of atherosclerotic lesions. The early stage of atherosclerosis is an inflammatory process that starts with the penetration of low density lipoproteins in the intima and with their oxidation. This phenomenon is closely linked to the local blood flow dynamics. Extending a previous work [5] that was mainly restricted to a one-dimensional setting, we couple a simple lesion growth model relying on the biomolecular process that takes place in the intima with blood flow dynamics and mass transfer. We perform numerical simulations on a two-dimensional geometry taken from [6,7] that mimicks a carotid artery deformed by a perivascular cast and we compare the numerical results with experimental data.

  10. Evaluation of the Pullback Atherectomy Catheter in the Treatment of Lower Limb Vascular Disease

    International Nuclear Information System (INIS)

    Grubnic, Sisa; Heenan, Susan D.; Buckenham, Timothy M.; Belli, Anna-Maria

    1996-01-01

    Purpose: To evaluate prospectively the Pullback Atherectomy Catheter (PAC) in terms of its technical success and 1-year patency in the treatment of lower limb vascular disease. Methods: Thirty-nine PAC procedures were performed in 34 patients to treat atherosclerotic disease (occlusive in 51%) of the femoropopliteal arteries, including four cases of graft neointimal hyperplasia and three dissection flaps. Follow-up was by ankle - brachial indices at 24 hr and 1 month, and arteriography at 6 and 12 months. Results: Technical success was achieved in 38 of 39 procedures (97.4%). There was a reduction in mean stenosis from 89.4% to 12.1%, but 69.2% of procedures required additional balloon dilatation to achieve an adequate arterial lumen. Complications followed 15.4% of procedures, a third of which required surgery. Conclusion: The PAC is an easy and relatively safe catheter to use, but does not provide a satisfactory arterial lumen without additional percutaneous transluminal angioplasty (PTA). It proved to be effective, however, in the treatment of graft neointimal hyperplasia and in the resection of obstructive intimal flaps following PTA

  11. Biomarkers of atherosclerotic plaque vulnerability and their clinical significance

    Directory of Open Access Journals (Sweden)

    Ran LIU

    2016-09-01

    Full Text Available Inflammatory reaction plays a crucial role in the occurence and development of atherosclerosis. Both basic and clinical trials have provided evidence that the expression of inflammatory biomarkers are closely related with the degree of atherosclerosis. Treatment towards inflammatory factors would bring benefit to atherosclerotic patients. This review highlighted the mechanistic rationale and specific therapies targeting traditional and novel inflammatory biomarkers, including C-reactive protein (CRP, interleukin-17 (IL-17, secretory phospholipase A2 (sPLA2, lipoprotein-associated phospholipase A2 (Lp-PLA2, endoglin, chemokine receptor and 5-lipoxygenase (5-LO, so as to review its mechanism of action and treatment prospect. DOI: 10.3969/j.issn.1672-6731.2016.09.004

  12. Assessment of atherosclerotic luminal narrowing of coronary arteries based on morphometrically generated visual guides.

    Science.gov (United States)

    Barth, Rolf F; Kellough, David A; Allenby, Patricia; Blower, Luke E; Hammond, Scott H; Allenby, Greg M; Buja, L Maximilian

    Determination of the degree of stenosis of atherosclerotic coronary arteries is an important part of postmortem examination of the heart, but, unfortunately, estimation of the degree of luminal narrowing can be imprecise and tends to be approximations. Visual guides can be useful to assess this, but earlier attempts to develop such guides did not employ digital technology. Using this approach, we have developed two computer-generated morphometric guides to estimate the degree of luminal narrowing of atherosclerotic coronary arteries. The first is based on symmetric or eccentric circular or crescentic narrowing of the vessel lumen and the second on either slit-like or irregularly shaped narrowing of the vessel lumens. Using the Aperio ScanScope XT at a magnification of 20× we created digital whole-slide images of 20 representative microscopic cross sections of the left anterior descending (LAD) coronary artery, stained with either hematoxylin and eosin (H&E) or Movat's pentachrome stain. These cross sections illustrated a variety of luminal profiles and degrees of stenosis. Three representative types of images were selected and a visual guide was constructed with Adobe Photoshop CS5. Using the "Scale" and "Measurement" tools, we created a series of representations of stenosis with luminal cross sections depicting 20%, 40%, 60%, 70%, 80%, and 90% occlusion of the LAD branch. Four pathologists independently reviewed and scored the degree of atherosclerotic luminal narrowing based on our visual guides. In addition, digital technology was employed to determine the degree of narrowing by measuring the cross-sectional area of the 20 microscopic sections of the vessels, first assuming no narrowing and then comparing this to the percent of narrowing determined by precise measurement. Two of the observers were very experienced general autopsy pathologists, one was a first-year pathology resident on his first rotation on the autopsy service, and the fourth observer was a

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

    Science.gov (United States)

    2014-01-01

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

  14. Buddleja officinalis suppresses high glucose-induced vascular smooth muscle cell proliferation: role of mitogen-activated protein kinases, nuclear factor-kappaB and matrix metalloproteinases.

    Science.gov (United States)

    Lee, Yun Jung; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2010-02-01

    Diabetes mellitus is a well-established risk factor for vascular diseases caused by atherosclerosis. In the development of diabetic atherogenesis, vascular smooth muscle cell proliferation is recognized as a key event. Thus, we aimed to investigate whether an ethanol extract of Buddleja officinalis (EBO) suppresses high glucose-induced proliferation in primary cultured human aortic smooth muscle cells (HASMC). [(3)H]-thymidine incorporation revealed that incubation of HASMC with a high concentration of glucose (25 mmol/L) increased cell proliferation. The expression levels of cell cycle protein were also increased by treatment with high glucose concentration. Pretreatment of HASMC with EBO significantly attenuated the increase of high glucose-induced cell proliferation as well as p38 mitogen-activated protein kinases (MAPK) and JNK phosphorylation. EBO suppressed high glucose-induced matrix metalloproteinase (MMP)-9 activity in a dose-dependent manner. In addition, EBO suppressed nuclear factor-kappaB (NF-kappaB) nuclear translocation and transcriptional activity in high glucose conditions. Taken together, the present data suggest that EBO could suppress high glucose-induced atherosclerotic processes through inhibition of p38, JNK, NF-kappaB and MMP signal pathways in HASMC.

  15. EMMPRIN (CD147/basigin) mediates platelet-monocyte interactions in vivo and augments monocyte recruitment to the vascular wall.

    Science.gov (United States)

    Schulz, C; von Brühl, M-L; Barocke, V; Cullen, P; Mayer, K; Okrojek, R; Steinhart, A; Ahmad, Z; Kremmer, E; Nieswandt, B; Frampton, J; Massberg, S; Schmidt, R

    2011-05-01

    Platelets play a central role in hemostasis, in inflammatory diseases such as atherosclerosis, and during thrombus formation following vascular injury. Thereby, platelets interact intensively with monocytes and enhance their recruitment to the vascular wall. To investigate the role of the extracellular matrix metalloproteinase inducer (EMMPRIN) in platelet-monocyte interactions. Isolated human monocytes were perfused in vitro over firmly adherent platelets to allow investigation of the role of EMMPRIN in platelet-monocyte interactions under flow conditions. Monocytes readily bound to surface-adherent platelets. Both antibody blockade and gene silencing of monocyte EMMPRIN substantially attenuated firm adhesion of monocytes to platelets at arterial and venous shear rates. In vivo, platelet interactions with the murine monocyte cell line ANA-1 were significantly decreased when ANA-1 cells were pretreated with EMMPRIN-silencing small interfering RNA prior to injection into wild-type mice. Using intravital microscopy, we showed that recruitment of EMMPRIN-silenced ANA-1 to the injured carotid artery was significantly reduced as compared with control cells. Further silencing of EMMPRIN resulted in significantly fewer ANA-1-platelet aggregates in the mouse circulation as determined by flow cytometry. Finally, we identified glycoprotein (GP)VI as a critical corresponding receptor on platelets that mediates interaction with monocyte EMMPRIN. Thus, blocking of GPVI inhibited the effect of EMMPRIN on firm monocyte adhesion to platelets under arterial flow conditions in vitro, and abrogated EMMPRIN-mediated platelet-monocyte aggregate formation in vivo. EMMPRIN supports platelet-monocyte interactions and promotes monocyte recruitment to the arterial wall. Therefore, EMMPRIN might represent a novel target to reduce vascular inflammation and atherosclerotic lesion development. © 2011 International Society on Thrombosis and Haemostasis.

  16. 64Cu-DOTATATE PET/MRI for detection of activated macrophages in carotid atherosclerotic plaques

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  17. Platelet activation, function, and reactivity in atherosclerotic carotid artery stenosis: a systematic review of the literature.

    LENUS (Irish Health Repository)

    Kinsella, J A

    2012-09-27

    An important proportion of transient ischemic attack or ischemic stroke is attributable to moderate or severe (50-99%) atherosclerotic carotid stenosis or occlusion. Platelet biomarkers have the potential to improve our understanding of the pathogenesis of vascular events in this patient population. A detailed systematic review was performed to collate all available data on ex vivo platelet activation and platelet function\\/reactivity in patients with carotid stenosis. Two hundred thirteen potentially relevant articles were initially identified; 26 manuscripts met criteria for inclusion in this systematic review. There was no consistent evidence of clinically informative data from urinary or soluble blood markers of platelet activation in patients with symptomatic moderate or severe carotid stenosis who might be considered suitable for carotid intervention. Data from flow cytometry studies revealed evidence of excessive platelet activation in patients in the early, sub-acute, or late phases after transient ischemic attack or stroke in association with moderate or severe carotid stenosis and in asymptomatic moderate or severe carotid stenosis compared with controls. Furthermore, pilot data suggest that platelet activation may be increased in recently symptomatic than in asymptomatic severe carotid stenosis. Excessive platelet activation and platelet hyperreactivity may play a role in the pathogenesis of first or subsequent transient ischemic attack or stroke in patients with moderate or severe carotid stenosis. Larger longitudinal studies assessing platelet activation status with flow cytometry and platelet function\\/reactivity in symptomatic vs. asymptomatic carotid stenosis are warranted to improve our understanding of the mechanisms responsible for transient ischemic attack or stroke.

  18. Three-dimensional dynamic contrast-enhanced MRI for the accurate, extensive quantification of microvascular permeability in atherosclerotic plaques

    NARCIS (Netherlands)

    Calcagno, Claudia; Lobatto, Mark E.; Dyvorne, Hadrien; Robson, Philip M.; Millon, Antoine; Senders, Max L.; Lairez, Olivier; Ramachandran, Sarayu; Coolen, Bram F.; Black, Alexandra; Mulder, Willem J. M.; Fayad, Zahi A.

    2015-01-01

    Atherosclerotic plaques that cause stroke and myocardial infarction are characterized by increased microvascular permeability and inflammation. Dynamic contrast-enhanced MRI (DCE-MRI) has been proposed as a method to quantify vessel wall microvascular permeability in vivo. Until now, most DCE-MRI

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

    Directory of Open Access Journals (Sweden)

    Nazanin Hakimzadeh

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

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

    Science.gov (United States)

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

    2017-01-01

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

  1. Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Helena U Westergren

    Full Text Available Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

  2. Combined micro-PIXE and NIR Raman spectroscopic plaque characterisation in a human atherosclerotic aorta sample

    International Nuclear Information System (INIS)

    Brands, P.J.M.; Poll, S.W.E. van de; Quaedackers, J.A.; Mutsaers, P.H.A.; Puppels, G.J.; Laarse, A. van der; Voigt, M.J.A. de

    2001-01-01

    Raman spectroscopy can be applied to characterise the chemical composition of an atherosclerotic plaque in vivo. In the near future this technique may become available for use in (coronary) arteries of living patients. For this moment, Raman spectroscopy is applied on artery samples in vitro, to study progression and regression of atherosclerotic plaque. Raman spectroscopy provides chemical information on a molecular basis. In this study, micro-particle induced X-ray emission (micro-PIXE) is applied to provide additional information on the elemental composition of the artery. Furthermore, the combined techniques allow for validation of the structures studied with Raman spectroscopy. This study proves that it is possible to combine and compare both techniques using the same region on the same sample if proper sample preparation is applied. Comparison shows that regions appearing in the Raman spectroscopy results can also be distinguished in micro-PIXE and backscattering spectroscopy (BS) distributions and vice versa. Combining both techniques makes it possible to separate phospholipids from triglycerides. Combined Raman spectroscopy and micro-PIXE/BS is recommended for studying progression and regression of atherosclerosis

  3. The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

    DEFF Research Database (Denmark)

    McMurray, John; Solomon, Scott; Pieper, Karen

    2006-01-01

    failure, most treated with an ACE inhibitor). One of the main active controlled trials was confounded by a blood pressure difference between treatments. METHODS: We compared the effects of captopril, valsartan, and their combination on atherosclerotic events in 14,703 patients randomized in the Valsartan...... in Acute Myocardial Infarction Trial (VALIANT). RESULTS: The number of individuals adjudicated as having a fatal or non-fatal MI in the captopril group was 559 (total investigator reported events 798), 587 (796) in the valsartan group, and 554 (756) in the combination group; valsartan versus captopril, p...... = 0.651 (0.965); combination versus captopril, p = 0.187 (0.350). Overall, all atherosclerotic events examined occurred at a similar frequency in the captopril and valsartan groups. CONCLUSIONS: Angiotensin receptor blockers appear to be as effective as ACE inhibitors in reducing atherosclerotic...

  4. Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation.

    Science.gov (United States)

    Mo, Jiao; Yang, Renhua; Li, Fan; Zhang, Xiaochao; He, Bo; Zhang, Yue; Chen, Peng; Shen, Zhiqiang

    2018-03-15

    Scutellarin is the major constituent responsible for the clinical benefits of Erigeron breviscapus (Vant.) Hand.-Mazz which finds a long history of ethnopharmacological use in Traditional Chinese Medicine. Scutellarin as a pure compound is now under investigation for its protections against various tissue injuries. This study aims to examine the effects of scutellarin on oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage, and then to evaluate the therapeutic efficacy of scutellarin in preventing atherosclerosis in rats. Radical scavenging ability of scutellarin was determined in vitro. Impact of scutellarin on endothelium-dependent relaxation (EDR) of rabbit thoracic aortic rings upon 1, 1-diphenyl-2-picrylhydrazyl (DPPH) challenge was measured. Influences of scutellarin pre-treatment on the levels of reactive oxygen species (ROS), activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase and catalase, and the expression of SOD1 and NADPH oxidase 4 (Nox4) in human umbilical vein endothelial cells (HUVECs) injured by H 2 O 2 were examined. Anti-atherosclerotic effect of scutellarin was evaluated in rats fed with high fat diet (HFD). Scutellarin showed potent antioxidant activity in vitro. Pretreatment of scutellarin retained the EDR of rabbit thoracic aortic rings damaged by DPPH. In H 2 O 2 injured-HUVECs the deleterious alterations in ROS levels and antioxidant enzymes activity were reversed by scutellarin and the mRNA and protein expression of SOD1 and Nox4 were restored also. Oral administration of scutellarin dose-dependently ameliorated hyperlipidemia in HFD-fed rats and alleviated oxidative stress in rat serum, mimicking the effects of reference drug atorvastatin. Scutellarin protects against oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage in vitro and prevents atherosclerosis in vivo through antioxidation. The results rationalize further investigation into the

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

    Science.gov (United States)

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

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

  6. Triactome: neuro-immune-adipose interactions. Implication in vascular biology

    Directory of Open Access Journals (Sweden)

    George Nikov Chaldakov

    2014-04-01

    Full Text Available Understanding how the precise interactions of nerves, immune cells and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae: intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue, we recently designated tunica adiposa (in brief, adiposa like intima, media, adventitia. According to present paradigm, atherosclerosis is an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. Periadventitial adipose tissue expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic signaling proteins collectively dubbed adipokines. However, the role of perivascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro-immune-adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Vascular cognitive impairments in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    I. V. Rogova

    2015-01-01

    Full Text Available Objective: to study the specific features of development of cognitive impairments (CIs, the role of traditional cardiovascular risk factors and renal failure-induced factors in patients with Stages I–IV chronic kidney disease (CKD and to assess an association of CIs with the signs of vascular wall remodeling in them. Patients and methods. Fifty-one patients aged 53±10 years with CKD were examined. Among them, there were 20 patients with Stages I–II CKD: a glomerular filtration rate (GFR of і60 ml/min/1.73 m2, signs of renal lesion; 20 with Stages III CKD: a GFR of <60–30 ml/min/1.73 m2, and 11 with Stages VI CKD: a GFR of <30–15 ml/min/1.73 m2. Results and discussion. CIs were more common in the patients with Stages III–IV than in those with Stages I–II, as shown by the scores of the mini-mental state examination (p<0.001, the frontal assessment battery (p=0.001, and the regulatory function test (p<0.001. These tests showed that the magnitude of CIs increased with the higher stage of CKD. Stages III–IV CKD is an independent predictor of CIs in persons with predialysis-stage kidney lesion. CIs were found to be related to hyperhomocysteinemia, anemia, abdominal obesity, left ventricular hypertrophy, and patient age. The signs of atherosclerotic lesion of the common carotid arteries and the indicators of arterial stiffness were also associated with the incidence and magnitude of CIs in CKD. The detection of CIs in patients with early CKD allows one to timely initiate adequate therapy aimed particularly at improving cerebral circulation, eliminating the impact of risk factors, and slowing down the vascular remodeling. The management tactics for patients with CKD must involve the identification and correction of cardiovascular risk factors, and duplex scanning of the wall of the common carotid arteries may be used as a noninvasive method to assess the risk of the development and progression of CIs in predialysis CKD. 

  9. 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.

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

    International Nuclear Information System (INIS)

    Li Mingli; Sun Jie; Chang Xiaoyan; Jin Zhengyu

    2011-01-01

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

  11. 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

  12. Lipocalin-type prostaglandin D synthase is not a biomarker of atherosclerotic manifestations

    DEFF Research Database (Denmark)

    Hosbond, Susanne E; Diederichsen, Axel C P; Pedersen, Lise

    2014-01-01

    tool in the setting of stable coronary artery disease. We set out to investigate if measurement of concentrations of these biomarkers could be used to differentiate between four groups of individuals with different atherosclerotic manifestations. METHODS: A total of 120 individuals from four equal...... gender- and age-matched groups were studied: (i) no previous cardiovascular disease (CVD) and no coronary calcifications [CAC-negative group], (ii) no previous CVD but evidence of severe coronary calcifications [CAC-positive group], (iii) acute coronary syndrome [ACS-group], and (iv) clinical stable...

  13. Angiographic assessment of atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy.

    Science.gov (United States)

    Çildağ, Mehmet B; Ertuğrul, Bülent M; Köseoğlu, Ömer Fk; Çildağ, Songül; Armstrong, David G

    2018-06-01

    The aim of this study was to investigate atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy and compare them with patients with diabetic foot without charcot neuro-arthropathy. This retrospective study consists of 78 patients with diabetic foot who had lower extremity angiography with antegrade approach. All patients were classified into two groups; neuro ischemic wounds with charcot neuro-arthropathy (30/78) and without charcot neuro-arthropathy (48/78).Atherosclerotic load at the side of diabetic foot was determined by using the Bollinger angiogram scoring method. Comparison of atherosclerotic load between the two groups was performed. The mean of total and infrapopliteal level angiogram scoring of all patients was 33.3 (standard deviation, sd:±17.2) and 29.3 (sd:±15.6), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds with charcot neuro-arthropathy group was 18.1 (sd:±11.6) and 15.7 (sd:±10.4), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds without charcot neuro-arthropathy group was 42.8 (sd:±12.7) and 37.7 (sd:±12.0), respectively. There was a statistically significant difference between the two groups of mean total and infrapopliteal angiogram scoring (p diabetic foot and chronic charcot neuro-arthropathy is significantly less than in patients with neuroischemic diabetic foot wounds without chronic charcot neuro-arthropathy. Copyright © 2017. Published by Elsevier Taiwan LLC.

  14. Contrast enhancement by differently sized paramagnetic MRI contrast agents in mice with two phenotypes of atherosclerotic plaque

    NARCIS (Netherlands)

    van Bochove, Glenda S.; Paulis, Leonie E. M.; Segers, Dolf; Mulder, Willem J. M.; Krams, Rob; Nicolay, Klaas; Strijkers, Gustav J.

    2011-01-01

    Interest in the use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of three differently sized gadolinium-based contrast agents to permeate different mouse plaque phenotypes was evaluated with MRI. A

  15. Early detection of premature subclinical coronary atherosclerosis in systemic lupus erythematosus patients

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    Khaled Mohamed Said Othman

    2013-12-01

    Conclusion: Pre-menopausal SLE female patients free from clinical atherosclerotic vascular disease have an increased number of atherosclerotic plaques and CCS, which correlate positively with SLEDAI disease activity score, serum CRP, anticardiolipin antibodies, sICAM-1, E-Selectin, LDL level, total cholesterol level, and cumulative prednisone dose. In addition, we conclude that MDCT is a non-invasive, sensitive, reproducible, and reliable tool for accurate measurement of coronary calcification.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  17. Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles.

    Science.gov (United States)

    Nie, Shufang; Zhang, Jia; Martinez-Zaguilan, Raul; Sennoune, Souad; Hossen, Md Nazir; Lichtenstein, Alice H; Cao, Jun; Meyerrose, Gary E; Paone, Ralph; Soontrapa, Suthipong; Fan, Zhaoyang; Wang, Shu

    2015-12-28

    Current approaches to the diagnosis and therapy of atherosclerosis cannot target lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing inflammatory responses. The presence of these cells is positively associated with lesion progression, severity and destabilization. Hence, they are an important diagnostic and therapeutic target. The objective of this study was to noninvasively assess the distribution and accumulation of intimal macrophages using CD36-targeted nanovesicles. Soy phosphatidylcholine was used to synthesize liposome-like nanovesicles. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine was incorporated on their surface to target the CD36 receptor. All in vitro data demonstrate that these targeted nanovesicles had a high binding affinity for the oxLDL binding site of the CD36 receptor and participated in CD36-mediated recognition and uptake of nanovesicles by macrophages. Intravenous administration into LDL receptor null mice of targeted compared to non-targeted nanovesicles resulted in higher uptake in aortic lesions. The nanovesicles co-localized with macrophages and their CD36 receptors in aortic lesions. This molecular target approach may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophage accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability thereby facilitate early lesion detection and targeted delivery of therapeutic compounds to intimal macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Prognosis of non-significant coronary atherosclerotic disease detected by coronary artery tomography

    Energy Technology Data Exchange (ETDEWEB)

    Barros, Marcio Vinicius Lins; Siqueira, Bruna Pinto; Guimaraes, Carolina Camargos Braichi; Cruz, David Filipe Silva; Guimaraes, Leiziane Assuncao Alves; Lima, Maicom Marcio Perigolo, E-mail: marciovlbarros@gmail.com [Faculdade de Saude e Ecologia Humana, Vespasiano, MG (Brazil); Nunes, Maria do Carmo Pereira [Universidade de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina; Siqueira, Maria Helena Albernaz [Hospital Materdei, Belo Horizonte, MG (Brazil)

    2015-07-15

    Introduction: Although studies have shown high diagnostic accuracy of coronary tomography (CT) in detecting coronary artery disease (CAD), data on the prognostic value of this method in patients with no significant coronary obstruction are limited. Objective: To evaluate the value of CT in predicting adverse events in patients with suspected CAD and no significant coronary obstruction. Methods: We prospectively evaluated 440 patients between January 2008 and July 2013 by MDCT, diagnosed with no significant obstruction or no atherosclerotic coronary obstruction with an average follow-up of 33 months. The outcomes evaluated were: cardiac death, myocardial infarction, unstable angina associated with hospitalization or coronary artery bypass grafting. Results: Of the 440 patients studied, 295 (67%) were men with mean age 55.9 ± 12.0 years. Non-significant obstruction was found in 152 (35%) of the patients and there were 49 (11%) outcomes. In the multivariate analysis using the Cox regression model, the predictors of clinical outcomes were non-significant obstruction on CT (hazard ratio 3.51; 95% CI 1.73 - 7.8; p <0.01), age and hypertension. Non-significant obstruction on CT was associated with adverse clinical outcomes and survival analysis showed a significant difference (log-rank 24.6; p <0.01) in predicting these outcomes. Conclusion: The detection of non-significant atherosclerotic obstruction by CT was associated with the presence of adverse events in patients with suspected CAD, which may prove useful in the risk stratification of these patients. (author)

  19. The formation of atherosclerotic plaque, its destabilisation and diagnostics

    Directory of Open Access Journals (Sweden)

    Piotr Kaźmierski

    2014-04-01

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

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

    DEFF Research Database (Denmark)

    Karadimou, Glykeria; Folkersen, Lasse; Berg, Martin

    2016-01-01

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

  1. Short-term effect of severe exposure to methylmercury on atherosclerotic heart disease and hypertension mortality in Minamata.

    Science.gov (United States)

    Inoue, Sachiko; Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

    2012-02-15

    Recent studies suggest potential adverse effects of methylmercury exposure on myocardial infarction and hypertension, although the evidence is still limited. We thus evaluated this association using age-standardized mortality ratios (ASMRs) in Minamata, where severe methylmercury poisoning had occurred. We obtained mortality data from annual vital statistics and demographic statistics from census. We then compared mortality of atherosclerotic heart disease including degenerative heart disease and hypertension in Minamata-city with those in Kumamoto Prefecture, which includes Minamata city, as a control. We estimated ASMRs and 95% confidence intervals (CIs) during the period from 1953 to 1970. ASMRs of atherosclerotic heart disease were continuously decreased during the period from 1953 to 1967. In contrast, the ASMR of hypertension was significantly elevated during the period from 1963 to 1967 (SMR=1.38, CI; 1.06-1.80); but they decreased later. Although dilution is present in this ecological study, our study supports the notion that methylmercury exposure induces hypertension. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Proinflammatory Stimulation of Toll-Like Receptor 9 with High Dose CpG ODN 1826 Impairs Endothelial Regeneration and Promotes Atherosclerosis in Mice.

    Directory of Open Access Journals (Sweden)

    Alexander O Krogmann

    Full Text Available Toll-like receptors (TLR of the innate immune system have been closely linked with the development of atherosclerotic lesions. TLR9 is activated by unmethylated CpG motifs within ssDNA, but also by CpG motifs in nucleic acids released during vascular apoptosis and necrosis. The role of TLR9 in vascular disease remains controversial and we sought to investigate the effects of a proinflammatory TLR9 stimulation in mice.TLR9-stimulation with high dose CpG ODN at concentrations between 6.25 nM to 30 nM induced a significant proinflammatory cytokine response in mice. This was associated with impaired reendothelialization upon acute denudation of the carotid and increased numbers of circulating endothelial microparticles, as a marker for amplified endothelial damage. Chronic TLR9 agonism in apolipoprotein E-deficient (ApoE-/- mice fed a cholesterol-rich diet increased aortic production of reactive oxygen species, the number of circulating endothelial microparticles, circulating sca-1/flk-1 positive cells, and most importantly augmented atherosclerotic plaque formation when compared to vehicle treated animals. Importantly, high concentrations of CpG ODN are required for these proatherogenic effects.Systemic stimulation of TLR9 with high dose CpG ODN impaired reendothelialization upon acute vascular injury and increased atherosclerotic plaque development in ApoE-/- mice. Further studies are necessary to fully decipher the contradictory finding of TLR9 agonism in vascular biology.

  3. Role of integrin-linked kinase in vascular smooth muscle cells: Regulation by statins and angiotensin II

    International Nuclear Information System (INIS)

    Friedrich, Erik B.; Clever, Yvonne P.; Wassmann, Sven; Werner, Nikos; Boehm, Michael; Nickenig, Georg

    2006-01-01

    Our goal was to characterize the role of integrin-linked kinase (ILK) in vascular smooth muscle cells (VSMC), which play a crucial role in atherogenesis. Transfection of VSMC with wild-type and dominant-negative ILK cDNA constructs revealed that ILK mediates migration and proliferation of VSMC but has no effect on VSMC survival. The pro-atherogenic mediator angiotensin II increases ILK protein expression and kinase activity while statin treatment down-regulates ILK in VSMC. Functionally, ILK is necessary for angiotensin II-mediated VSMC migration and proliferation. In VSMC transduced with dominant-negative ILK, statins mediate an additive inhibition of VSMC migration and proliferation, while transfection with wild-type ILK is sufficient to overcome the inhibitory effects of statin treatment on VSMC migration and proliferation. In vivo, ILK is expressed in VSMC of aortic sections from wild-type mice where it is down-regulated following statin treatment and up-regulated following induction of atherosclerosis in apoE-/- mice. These data identify ILK as a novel target in VSMC for anti-atherosclerotic therapy

  4. Diagnóstico y tratamiento de la enfermedad carotídea aterosclerótica extracraneal asintomática Diagnosis and treatment of asymptomatic extracranial atherosclerotic carotid artery disease

    Directory of Open Access Journals (Sweden)

    Luciano A. Sposato

    2011-12-01

    Full Text Available La enfermedad aterosclerótica asintomática de la arteria carótida interna extracraneal alcanza una prevalencia de hasta el 12.5%. La angioplastia carotídea todavía no ha demostrado ser lo suficientemente segura y eficaz para prevenir el ACV isquémico en estos pacientes. Estudios aleatorizados demostraron que la endarterectomía carotídea es superior al tratamiento médico en cuanto a reducción del riesgo de ACV isquémico si es realizada por equipos con tasas de complicaciones (ACV o muerte menores que 3%. Sin embargo, los pacientes evaluados en estos estudios comenzaron a reclutarse hace más de 25 años, cuando la utilización de antiagregantes plaquetarios era menor que la actual, el tratamiento de la hipertensión arterial era menos efectivo y todavía no se usaban estatinas como componentes fundamentales de los esquemas de prevención vascular. La optimización de la calidad del tratamiento médico en las últimas décadas ha llevado a una significativa reducción del riesgo de ACV en pacientes no intervenidos quirúrgicamente. En base a estas observaciones y con la excepción de casos específicos, el tratamiento médico es la opción terapéutica de elección en pacientes con enfermedad aterosclerótica carotídea extracraneal asintomática.The reported prevalence of asymptomatic atherosclerotic disease of the extracranial internal carotid artery is up to 12.5%. Carotid angioplasty has not yet proven safe and effective enough to prevent ischemic stroke in these patients. Randomized studies showed that carotid endarterectomy is superior to medical therapy in reducing the risk of ischemic stroke when performed by surgical teams with complication rates (stroke or death of less than 3%. However, recruitment of these patients began more than 25 years ago, when the use of antiplatelet agents was lower than today, the treatment of hypertension was less effective than currently, and statins were not considered as key components of

  5. Pediatric vascular access

    International Nuclear Information System (INIS)

    Donaldson, James S.

    2006-01-01

    Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  7. Element analysis with a proton microprobe of early atherosclerotic lesions

    NARCIS (Netherlands)

    Roijers, R.B.

    2009-01-01

    Atherosclerosis is a progressive inflammatory vascular disease accompanied by a gradual build-up of cholesterol in the artery walls. The associated chronic inflammatory process leads to tissue damage in the vascular wall as a consequence of an excessive inflammatory response. Large calcified

  8. Temperature distribution in atherosclerotic coronary arteries: influence of plaque geometry and flow (a numerical study)

    International Nuclear Information System (INIS)

    Have, A G ten; Gijsen, F J H; Wentzel, J J; Slager, C J; Steen, A F W van der

    2004-01-01

    Intravascular coronary thermography is a method that may detect vulnerable, atherosclerotic plaques and is currently evaluated in a clinical setting. Active macrophages or enzymatic heat releasing processes in vulnerable plaques may act as heat sources. To better understand the parameters of influence on thermographic measurements, numerical simulations have been performed on a model of a coronary artery segment containing a heat source. Heat source parameters and flow were varied to study their influence on temperatures at the lumen wall. Maximal temperature differences at the lumen wall increased when the source volume increased and they differ with the source geometry. The simulations showed that blood flow acts as a coolant to the lumen wall. Blood flow decreased maximal temperatures depending on the source geometry, source volume and the maximal flow velocity. Influence of flow was highest for circumferentially extended sources, up to a factor 3.7, and lowest for longitudinally extended sources, down to a factor 1.9. When cap thickness increased, maximal temperatures decreased and the influence of flow increased. This study shows that correct interpretation of intravascular thermographic measurements requires data on the flow and on the morphologic characteristics of the atherosclerotic plaque

  9. Optimization of dual-wavelength intravascular photoacoustic imaging of atherosclerotic plaques using Monte Carlo optical modeling

    Science.gov (United States)

    Dana, Nicholas; Sowers, Timothy; Karpiouk, Andrei; Vanderlaan, Donald; Emelianov, Stanislav

    2017-10-01

    Coronary heart disease (the presence of coronary atherosclerotic plaques) is a significant health problem in the industrialized world. A clinical method to accurately visualize and characterize atherosclerotic plaques is needed. Intravascular photoacoustic (IVPA) imaging is being developed to fill this role, but questions remain regarding optimal imaging wavelengths. We utilized a Monte Carlo optical model to simulate IVPA excitation in coronary tissues, identifying optimal wavelengths for plaque characterization. Near-infrared wavelengths (≤1800 nm) were simulated, and single- and dual-wavelength data were analyzed for accuracy of plaque characterization. Results indicate light penetration is best in the range of 1050 to 1370 nm, where 5% residual fluence can be achieved at clinically relevant depths of ≥2 mm in arteries. Across the arterial wall, fluence may vary by over 10-fold, confounding plaque characterization. For single-wavelength results, plaque segmentation accuracy peaked at 1210 and 1720 nm, though correlation was poor (blood, a primary and secondary wavelength near 1210 and 1350 nm, respectively, may offer the best implementation of dual-wavelength IVPA imaging. These findings could guide the development of a cost-effective clinical system by highlighting optimal wavelengths and improving plaque characterization.

  10. Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

    Science.gov (United States)

    Green, Daniel J.; Hopman, Maria T. E.; Padilla, Jaume; Laughlin, M. Harold; Thijssen, Dick H. J.

    2017-01-01

    On the 400th anniversary of Harvey's Lumleian lectures, this review focuses on “hemodynamic” forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone via paracrine transduction provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the interrelationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions, and the implications for human health. Exercise modifies blood flow, luminal shear stress, arterial pressure, and tangential wall stress, all of which can transduce changes in arterial function, diameter, and wall thickness. There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute to the well-established decrease in cardiovascular risk attributed to physical activity. PMID:28151424

  11. Relative risk for cardiovascular atherosclerotic events after smoking cessation: 6–9 years excess risk in individuals with familial hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Kastelein John JP

    2006-10-01

    Full Text Available Abstract Background Smoking history is often di- or trichotomized into for example "never, ever or current smoking". However, smoking must be treated as a time-dependent covariate when lifetime data is available. In particular, individuals do not smoke at birth, there is usually a wide variation with respect to smoking history, and smoking cessation must also be considered. Methods Therefore we analyzed smoking as a time-dependent risk factor for cardiovascular atherosclerotic events in a cohort of 2400 individuals with familial hypercholesterolemia who were followed from birth until 2004. Excess risk after smoking-cessation was modelled in a Cox regression model with linear and exponential decaying trends. The model with the highest likelihood value was used to estimate the decay of the excess risk of smoking. Results Atherosclerotic events were observed in 779 patients with familial hypercholesterolemia and 1569 individuals had a smoking history. In the model with the highest likelihood value the risk reduction of smoking after cessation follows a linear pattern with time and it appears to take 6 to 9 years before the excess risk is reduced to zero. The risk of atherosclerotic events due to smoking was estimated as 2.1 (95% confidence interval 1.5; 2.9. Conclusion It was concluded that excess risk due to smoking declined linearly after cessation in at least six to nine years.

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

    Directory of Open Access Journals (Sweden)

    Silviu Stanciu

    2016-07-01

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

  13. Comparison of osteoprotegerin to traditional atherosclerotic risk factors and high-sensitivity C-reactive protein for diagnosis of atherosclerosis

    DEFF Research Database (Denmark)

    Mogelvang, Rasmus; Pedersen, Sune Holm; Flyvbjerg, Allan

    2012-01-01

    Atherosclerosis is the main cause of cardiovascular disease, but the extent of atherosclerosis in individual patients is difficult to estimate. A biomarker of the atherosclerotic burden would be very valuable. The aim of the present study was to evaluate the association of plasma osteoprotegerin ...

  14. 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...

  15. Vascular Access in Children

    International Nuclear Information System (INIS)

    Krishnamurthy, Ganesh; Keller, Marc S.

    2011-01-01

    Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the “expert procedural pyramid” is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    ) and an additional ipsilateral internal carotid artery stenosis of greater than 60% were recruited. FDG uptake in the carotids was determined by PET/computed tomography and expressed as mean and maximal standardized uptake values (SUVmean and SUVmax). The atherosclerotic plaques were subsequently recovered...... by carotid endarterectomy. The gene expression of markers of vulnerability - CD68, IL-18, matrix metalloproteinase 9, cathepsin K, GLUT-1, and hexokinase type II (HK2) - were measured in plaques by quantitative PCR. RESULTS: In a multivariate linear regression model, GLUT-1, CD68, cathepsin K, and HK2 gene...... expression remained in the final model as predictive variables of FDG accumulation calculated as SUVmean (R=0.26, PK, and HK2 gene expression as independent predictive variables of FDG accumulation calculated...

  17. Relationship between aortic valve calcification and the severity of coronary atherosclerotic disease.

    Science.gov (United States)

    Qian, Juying; Chen, Zhangwei; Ge, Junbo; Ma, Jianying; Chang, Shufu; Fan, Bing; Liu, Xuebo; Ge, Lei

    2010-07-01

    Aortic valve calcification (AVC), which has been confirmed to be associated with various risk factors of cardiac disease, is common in the elderly and associated with increased cardiovascular mortality. It has been hypothesized that AVC is associated with coronary atherosclerotic disease, and its severity. Between July 2007 and November 2007, a total of 235 patients with chest pain or chest distress were admitted to the authors' institution for coronary angiography. The severity of coronary atherosclerotic disease (CAD) was evaluated by the Gensini score, the number of stenosed vessels, and the prevalence of total occlusion. All patients underwent transthoracic echocardiography to detect AVC. Patients with CAD had a higher prevalence of AVC than those without CAD (44% versus 26%, p = 0.005). Likewise, the prevalence of AVC was significantly higher in patients with a higher Gensini score than in those with a lower score. Patients with AVC had a higher prevalence of CAD, and higher Gensini scores and numbers of stenosed coronary arteries, even after stratification by age (65 years). On multivariable logistic regression analysis for CAD, the odds ratio (OR) of AVC was 2.315 (95% confidence interval (CI): 1.158-4.629, p = 0.018); this value was higher than that for total cholesterol (OR = 1.637, p = 0.008), lipoprotein-a (OR = 1.003, p = 0.015) and fibrinogen (OR = 1.009, p = 0.006), and marginally less than that for male gender (OR = 2.665, p = 0.005). Patients with AVC had a higher prevalence and greater severity of CAD.

  18. Atherosclerosis and clonal hematopoyesis: A new risk factor.

    Science.gov (United States)

    Páramo Fernández, José A

    Recent research has revealed that clonal hematopoyesis of indeterminate potential (CHIP) characterized by the acquisition of somatic mutations in hematopoietic stem cells, is not only a common age-related disorder and a premalignant condition, but it is also associated with the development of atherosclerotic vascular diseases. Mutations in DNMT3A, TET2 and ASXL1 were each individually associated with coronary heart disease, stroke and coronary calcification. Therefore, CHIP emerges as a new risk factor for atherosclerotic vascular pathologies and its detection may be relevant as a new therapeutic target in order to modify the natural course of the disease. Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  20. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

    Science.gov (United States)

    Parsons-Wingerter, Patricia

    2010-01-01

    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

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

    International Nuclear Information System (INIS)

    Rozie, S.; Weert, T.T. de; Monye, C. de; Homburg, P.J.; Tanghe, H.L.J.; Lugt, A. van der; Dippel, D.W.J.

    2009-01-01

    The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic artery. The contribution of different components was measured as the number of voxels within defined ranges of HU values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid artery. The severity of stenosis and PV were moderately correlated. Age and smoking were independently related to PV. Patients with hypercholesterolemia had significantly less lipid and more calcium in their plaques than patients without hypercholesterolemia. Other cardiovascular risk factors were not significantly related to PV or plaque composition. Luminal stenosis of the carotid artery partly reflects the amount of atherosclerotic carotid disease. Plaque volume and plaque composition are associated with cardiovascular risk factors. (orig.)

  2. 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.)

  3. The effect of aging on aortic atherosclerotic plaque inflammation and molecular calcification: A FDG and NaF PET CT imaging study

    DEFF Research Database (Denmark)

    Blomberg, Björn; Thomassen, Anders; Hildebrandt, Malene

    2013-01-01

    Objectives: Aging is an important independent determinant of plaque biology. This study aimed to investigate the effect of aging on atherosclerotic plaque inflammation and calcification metabolism. Methods: Thirteen healthy volunteers without traditional cardiovascular risk factors were...... and correlation coefficients summarized the data. Results: A quadratic relationship was observed between aging and aortic 18-FDG and aortic Na-18F avidity. A second order polynomial regression established that aging is a predictor of the degree of aortic plaque inflammation (R = 0.524; F statistic = 4.93; P = 0...... data, a quadratic relationship appears to exist between aging and plaque inflammation. Furthermore, a quadratic relationship was observed between aging and plaque calcification metabolism. In line with these observations, a linear relationship was observed between atherosclerotic plaque inflammation...

  4. Multiple anti-inflammatory and anti-atherosclerotic properties of red wine polyphenolic extracts: differential role of hydroxycinnamic acids, flavonols and stilbenes on endothelial inflammatory gene expression.

    Science.gov (United States)

    Calabriso, Nadia; Scoditti, Egeria; Massaro, Marika; Pellegrino, Mariangela; Storelli, Carlo; Ingrosso, Ilaria; Giovinazzo, Giovanna; Carluccio, Maria Annunziata

    2016-03-01

    The aim of the study was to evaluate the vascular anti-inflammatory effects of polyphenolic extracts from two typical South Italy red wines, the specific contribution of individual polyphenols and the underlying mechanisms of action. Human endothelial cells were incubated with increasing concentrations (1-50 μg/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1-25 μmol/L), including hydroxycinnamic acids (p-coumaric, caffeic and caftaric acids), flavonols (kaempferol, quercetin, myricetin) or stilbenes (trans-resveratrol, trans-piceid) before stimulation with lipopolysaccharide. Through multiple assays, we analyzed the endothelial-monocyte adhesion, the endothelial expression of adhesion molecules (ICAM-1, VCAM-1 and E-Selectin), monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF), as well as ROS intracellular levels and the activation of NF-κB and AP-1. Both PWPE and NWPE, already at 1 μg/mL, inhibited monocyte adhesion to stimulated endothelial cells, a key event in triggering vascular inflammation. They down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, as well as MCP-1 and M-CSF, at mRNA and protein levels. All polyphenols reduced intracellular ROS, and everything, except caftaric acid, inhibited the endothelial expression of adhesion molecules and MCP-1, although with different potency. Flavonols and resveratrol significantly reduced also the endothelial expression and release of M-CSF. The decrease in endothelial inflammatory gene expression was related to the inhibition of NF-κB and AP-1 activation but not to intracellular oxidative stress. This study showed multiple anti-inflammatory and anti-atherosclerotic properties of red wine polyphenolic extracts and indentified specific bioactive polyphenols which could counteract inflammatory diseases including atherosclerosis.

  5. Deficiency of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 accelerates atherogenesis in apolipoprotein E-deficient mice

    International Nuclear Information System (INIS)

    Akyuerek, Levent M.; Boehm, Manfred; Olive, Michelle; Zhou, Alex-Xianghua; San, Hong; Nabel, Elizabeth G.

    2010-01-01

    Cyclin-dependent kinase inhibitors, p21 Cip1 and p27 Kip1 , are upregulated during vascular cell proliferation and negatively regulate growth of vascular cells. We hypothesized that absence of either p21 Cip1 or p27 Kip1 in apolipoprotein E (apoE)-deficiency may increase atherosclerotic plaque formation. Compared to apoE -/- aortae, both apoE -/- /p21 -/- and apoE -/- /p27 -/- aortae exhibited significantly more atherosclerotic plaque following a high-cholesterol regimen. This increase was particularly observed in the abdominal aortic regions. Deficiency of p27 Kip1 accelerated plaque formation significantly more than p21 -/- in apoE -/- mice. This increased plaque formation was in parallel with increased intima/media area ratios. Deficiency of p21 Cip1 and p27 Kip1 accelerates atherogenesis in apoE -/- mice. These findings have significant implications for our understanding of the molecular basis of atherosclerosis associated with excessive proliferation of vascular cells.

  6. Fiber-optic system for dual-modality imaging of glucose probes 18F-FDG and 6-NBDG in atherosclerotic plaques.

    Directory of Open Access Journals (Sweden)

    Raiyan T Zaman

    Full Text Available Atherosclerosis is a progressive inflammatory condition that underlies coronary artery disease (CAD-the leading cause of death in the United States. Thus, the ultimate goal of this research is to advance our understanding of human CAD by improving the characterization of metabolically active vulnerable plaques within the coronary arteries using a novel catheter-based imaging system. The aims of this study include (1 developing a novel fiber-optic imaging system with a scintillator to detect both 18F and fluorescent glucose probes, and (2 validating the system on ex vivo murine plaques.A novel design implements a flexible fiber-optic catheter consisting of both a radio-luminescence and a fluorescence imaging system to detect radionuclide 18F-fluorodeoxyglucose (18F-FDG and the fluorescent analog 6-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-ylamino-6-Deoxyglucose (6-NBDG, respectively. Murine macrophage-rich atherosclerotic carotid plaques were imaged ex vivo after intravenous delivery of 18F-FDG or 6-NBDG. Confirmatory optical imaging by IVIS-200 and autoradiography were also performed.Our fiber-optic imaging system successfully visualized both 18F-FDG and 6-NBDG probes in atherosclerotic plaques. For 18F-FDG, the ligated left carotid arteries (LCs exhibited 4.9-fold higher radioluminescence signal intensity compared to the non-ligated right carotid arteries (RCs (2.6 × 10(4 ± 1.4 × 10(3 vs. 5.4 × 10(3 ± 1.3 × 10(3 A.U., P = 0.008. Similarly, for 6-NBDG, the ligated LCs emitted 4.3-fold brighter fluorescent signals than the control RCs (1.6 × 10(2 ± 2.7 × 10(1 vs. 3.8 × 10(1 ± 5.9 A.U., P = 0.002. The higher uptake of both 18F-FDG and 6-NBDG in ligated LCs were confirmed with the IVIS-200 system. Autoradiography further verified the higher uptake of 18F-FDG by the LCs.This novel fiber-optic imaging system was sensitive to both radionuclide and fluorescent glucose probes taken up by murine atherosclerotic plaques. In addition, 6-NBDG is a

  7. Anti-atherosclerotic effect of Cynodon dactylon extract on experimentally induced hypercholesterolemia in rats.

    Science.gov (United States)

    Pashaie, Belal; Hobbenaghi, Rahim; Malekinejad, Hassan

    2017-01-01

    Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg -1 ), moderate (200 mg kg -1 ) and maximum (400 mg kg -1 ) doses via gavages. The last group received atorvastatin (10 mg kg -1 ) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon -treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.

  8. Uterine Vascular Lesions

    Science.gov (United States)

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

  9. Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events.

    Science.gov (United States)

    Go, Alan S; Hsu, Chi-Yuan; Yang, Jingrong; Tan, Thida C; Zheng, Sijie; Ordonez, Juan D; Liu, Kathleen D

    2018-05-17

    AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge. We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records. Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12). AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge. Copyright © 2018 by the American Society of Nephrology.

  10. 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.

  11. 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.

  12. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    Science.gov (United States)

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. The correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease

    Directory of Open Access Journals (Sweden)

    Yan-Bing Xi

    2017-04-01

    Full Text Available Objective: To study the correlation of serum PDGF and Ang-2 contents with atherosclerotic plaque features in patients with coronary heart disease. Methods: A total of 80 patients with coronary heart disease who were treated in our hospital between January 2013 and April 2016 were collected as the observation group, and 50 healthy subjects who received medical examination in our hospital during the same period were selected as the normal control group. Serum PDGF and Ang-2 contents of two groups of patients were detected, and the observation group were further divided into the high PDGF group and low PDGF group (n = 40 as well as the high Ang-2 group and low Ang-2 group (n = 40 according to the median of PDGF and Ang-2 contents. Ultrasonic contrast technology was used to assess the atherosclerotic plaque characteristics in patients with coronary heart disease. Results: Serum PDGF and Ang-2 contents of observation group were significantly higher than those of control group; ultrasound parameters P and AUC levels of high PDGF group were higher than those of low PDGF group while Tp and MTT levels were lower than those of low PDGF group; ultrasound parameters P and AUC levels of high Ang-2 group were higher than those of low Ang-2 group while Tp and MTT levels were lower than those of low Ang-2 group. Conclusion: Serum PDGF and Ang-2 contents increase in patients with coronary heart disease and are negatively correlated with the atherosclerotic plaque stability.

  14. The vascular surgery workforce: a survey of consultant vascular surgeons in the UK, 2014.

    Science.gov (United States)

    Harkin, D W; Beard, J D; Shearman, C P; Wyatt, M G

    2015-04-01

    The purpose of this study was to describe the demographics, training, and practice characteristics of consultant vascular surgeons across the UK to provide an assessment of current, and inform future prediction of workforce needs. A questionnaire was developed using a modified Delphi process to generate questionnaire items. The questionnaire was emailed to all consultant vascular surgeons (n = 450) in the UK who were members of the Vascular Society of Great Britain & Ireland. 352 consultant vascular surgeons from 95 hospital trusts across the UK completed the survey (78% response rate). The mean age was 50.6 years old, the majority (62%) were mid-career, but 24% were above the age of 55. Currently, 92% are men and only 8% women. 93% work full-time, with 60% working >50 hours, and 21% working >60 hours per week. The average team was 5 to 6 (range 2-10) vascular surgeons, with 23% working in a large team of ≥8. 17% still work in small teams of ≤3. Over 90% of consultant vascular surgeons perform the major index vascular surgery procedures (aneurysm repair, carotid endarterectomy, infra-inguinal bypass, amputation). While 84% perform standard endovascular abdominal aortic aneurysm repair (EVAR), <50% perform more complex endovascular aortic therapy. The majority of vascular surgeons "like their job" (85%) and are "satisfied" (69%) with their job. 34% of consultant vascular surgeons indicated they were "extremely likely" to retire within the next 10 years. This study provides the first detailed analysis of the new specialty of vascular surgery as practiced in the UK. There is a need to plan for a significant expansion in the consultant vascular surgeon workforce in the UK over the next 10 years to maintain the status quo. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  15. Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries

    Science.gov (United States)

    McArdle, Sara; Chodaczek, Grzegorz; Ray, Nilanjan; Ley, Klaus

    2015-02-01

    Intravital multiphoton imaging of arteries is technically challenging because the artery expands with every heartbeat, causing severe motion artifacts. To study leukocyte activity in atherosclerosis, we developed the intravital live cell triggered imaging system (ILTIS). This system implements cardiac triggered acquisition as well as frame selection and image registration algorithms to produce stable movies of myeloid cell movement in atherosclerotic arteries in live mice. To minimize tissue damage, no mechanical stabilization is used and the artery is allowed to expand freely. ILTIS performs multicolor high frame-rate two-dimensional imaging and full-thickness three-dimensional imaging of beating arteries in live mice. The external carotid artery and its branches (superior thyroid and ascending pharyngeal arteries) were developed as a surgically accessible and reliable model of atherosclerosis. We use ILTIS to demonstrate Cx3cr1GFP monocytes patrolling the lumen of atherosclerotic arteries. Additionally, we developed a new reporter mouse (Apoe-/-Cx3cr1GFP/+Cd11cYFP) to image GFP+ and GFP+YFP+ macrophages "dancing on the spot" and YFP+ macrophages migrating within intimal plaque. ILTIS will be helpful to answer pertinent open questions in the field, including monocyte recruitment and transmigration, macrophage and dendritic cell activity, and motion of other immune cells.

  16. Fetuin-A and albumin alter cytotoxic effects of calcium phosphate nanoparticles on human vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Yana Dautova

    Full Text Available Calcification is a detrimental process in vascular ageing and in diseases such as atherosclerosis and arthritis. In particular, small calcium phosphate (CaP crystal deposits are associated with inflammation and atherosclerotic plaque de-stabilisation. We previously reported that CaP particles caused human vascular smooth muscle cell (VSMC death and that serum reduced the toxic effects of the particles. Here, we found that the serum proteins fetuin-A and albumin (≥ 1 µM reduced intracellular Ca2+ elevations and cell death in VSMCs in response to CaP particles. In addition, CaP particles functionalised with fetuin-A, but not albumin, were less toxic than naked CaP particles. Electron microscopic studies revealed that CaP particles were internalised in different ways; via macropinocytosis, membrane invagination or plasma membrane damage, which occurred within 10 minutes of exposure to particles. However, cell death did not occur until approximately 30 minutes, suggesting that plasma membrane repair and survival mechanisms were activated. In the presence of fetuin-A, CaP particle-induced damage was inhibited and CaP/plasma membrane interactions and particle uptake were delayed. Fetuin-A also reduced dissolution of CaP particles under acidic conditions, which may contribute to its cytoprotective effects after CaP particle exposure to VSMCs. These studies are particularly relevant to the calcification observed in blood vessels in patients with kidney disease, where circulating levels of fetuin-A and albumin are low, and in pathological situations where CaP crystal formation outweighs calcification-inhibitory mechanisms.

  17. 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

    Inflammation is a part of the initial process leading to atherosclerosis and cholesterol crystals (CC), found in atherosclerotic plaques, which are known to induce complement activation. The pentraxins C-reactive protein (CRP), long pentraxin 3 (PTX3), and serum amyloid P component (SAP) are seru...

  18. Targeted folate receptor β fluorescence imaging as a measure of inflammation to estimate vulnerability within human atherosclerotic carotid plaque

    NARCIS (Netherlands)

    Jager, Nynke A.; Westra, Johanna; van Dam, Gooitzen M.; Teteloshvili, Nato; Tio, Rene A.; Breek, Jan-Cees; Slart, Riemer H. J. A.; Boersma, Hendrikus H.; Low, Phillip S.; Bijl, Marc; Zeebregts, Clark J.

    UNLABELLED: The probability of atherosclerotic plaque rupture and its thrombotic sequelae are thought to be increased at sites of macrophage accumulation. Folate receptor β (FR-β) is present on activated macrophages but not on quiescent macrophages or other immune cells. By conjugating the ligand

  19. VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation

    International Nuclear Information System (INIS)

    Li, Shang; Dang, Yuan Ye; Oi Lam Che, Ginny; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

    2014-01-01

    In ischemic disorders such as chronic wounds and myocardial ischemia, there is inadequate tissue perfusion due to vascular insufficiency. Besides, it has been observed that prolonged use of anti-angiogenic agents in cancer therapy produces cardiovascular toxicity caused by impaired vessel integrity and regeneration. In the present study, we used VEGFR tyrosine kinase inhibitor II (VRI) to chemically induce vascular insufficiency in zebrafish in vivo and human umbilical vein endothelial cells (HUVEC) in vitro to further study the mechanisms of vascular morphogenesis in these pathological conditions. We also explored the possibility of treating vascular insufficiency by enhancing vascular regeneration and repair with pharmacological intervention. We observed that pretreatment of VRI induced blood vessel loss in developing zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression. The VRI-induced blood vessel loss in zebrafish could be restored by post-treatment of calycosin, a cardiovascular protective isoflavone. Similarly, VRI induced cytotoxicity and apoptosis in HUVEC which could be rescued by calycosin post-treatment. Further investigation of the underlying mechanisms showed that the PI3K/AKT/Bad cell survival pathway was a main contributor of the vascular regenerative effect of calycosin. These findings indicated that the cardiovascular toxicity in anti-angiogenic therapy was mainly caused by insufficient endothelial cell survival, suggesting its essential role in vascular integrity, repair and regeneration. In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities. - Highlights: • In vivo VRI model • Rescue effects of calycosin • Calycosin EC survival pathways

  20. Plasma-mediated vascular dysfunction in the reduced uterine perfusion pressure model of preeclampsia: a microvascular characterization.

    LENUS (Irish Health Repository)

    Walsh, Sarah K

    2012-01-31

    Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (P<0.001). Vasorelaxation was impaired in resistance vessels from RUPP compared with control rats (acetylcholine: R(max) 70+\\/-3 versus 92+\\/-1 [NP] and 93+\\/-3% [sham], P<0.01; bradykinin: 40+\\/-2 versus 62+\\/-2 [NP] and 59+\\/-4% [sham], P<0.001). Incubation of vessels from pregnant (but not virgin) animals with RUPP plasma overnight resulted in an attenuation of vasorelaxant responses (acetylcholine: 63+\\/-7 versus 86+\\/-2%, P<0.05; bradykinin: 35+\\/-5 versus 55+\\/-6%, P<0.001). The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N(omega)-nitro-l-arginine methyl ester (acetylcholine: 57+\\/-7 versus 63+\\/-7%, ns; bradykinin: 37+\\/-5 versus 35+\\/-5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels.

  1. Effects of onion extract on endogenous vascular H2S and adrenomedulin in rat atherosclerosis.

    Science.gov (United States)

    Li, Wei; Tang, Chaoshu; Jin, Hongfang; Du, Junbao

    2011-09-01

    This study aimed to explore the effect of onion extract on endogenous hydrogen sulfide (H2S) and adrenomedulin (ADM) and on atherosclerotic progression in rats with atherosclerosis (AS). Male Sprague-Dawley rats were randomly divided into control, AS and AS+onion groups. Ultrastructure of aorta and atherosclerotic lesions both in aorta and in coronary artery were detected. Plasma and aortic H2S were detected by using a sulfide- sensitive electrode. Plasma and aortic ADM was determined with radioimmunoassay. Cystathionine-γ-lyase (CSE), calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP1, RAMP2 and RAMP3) mRNA expressions were analysed. Glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and NO synthase (NOS) contents in plasma, SOD1, SOD2 and ICAM-1 expressions in aorta were detected. Rats in the AS group showed marked atherosclerotic lesions both in aorta and in coronary artery but decreased aortic H2S production. Decreased plasma and aortic ADM content, but increased levels of aortic CRLR, RAMP2 and RAMP3 mRNAs were observed. Plasma GSH-PX and SOD were reduced but MDA elevated. Plasma ICAM-1 and NO contents and iNOS activity were increased. Onion extract, however, lessened atherosclerotic lesions and increased endogenous aortic H2S production, but decreased plasma ADM content, aortic ADM content and aortic CRLR, RAMP2 and RAMP3 mRNAs. In addition, it increased plasma GSH-PX level and SOD activities but reduced MDA; it decreased inflammatory response but increased plasma eNOS activity and NO content. Onion extract exerted a marked antiatherogenic effect in association with the up-regulation of the endogenous CSE/H2S pathway but down-regulation of the ADM/CRLR family in atherosclerotic rats.

  2. The relationship of the gene polymorphisms of matrix metalloproteinase-1, -2, -3 and -9 to the progression of coronary atherosclerotic plaque

    International Nuclear Information System (INIS)

    Hu Jian; Lu Lin; Wu Liqun; Zhang Qi; Ding Feghua; Yang Zhenkun; Zhang Ruiyan; Zhang Jiansheng; Shen Weifeng

    2009-01-01

    Objective: To evaluate the influence of the gene polymorphisms of matrix metalloproteinase(mmp)-1, -2, -3 and -9 on coronary atherosclerotic plaque progression. Methods: During the period of January 2005-December 2008, 80 patients with coronary heart disease underwent two times coronary angiography at authors' hospital. Based on the angiographic findings, the patients were classified into plaque progression group (n = 31) and plaque non-progression group (n = 49). Coronary atherosclerotic plaque progression was arbitrarily defined as that the minimal lumen diameter (MLD) of coronary artery showed a decrease ≥ 0.4 mm on the second coronary angiography. The detailed history and clinical examination results were collected, including serum concentrations of lipid profiling, fasting glucose and hs-CRP. Genotypings for polymorphic variances of MMP-1 (-1607 G / GG), MMP-2 (-955 A / C), MMP-3 (-1612 5A / 6A ) and MMP-9 (-1562 C/T) were performed by polymerase chain reaction (PCR) and sequencing analysis in two groups. Comparison of the clinical characteristics and polymorphisms between two groups was made to assess their effects on coronary atherosclerotic plaque progression. Results: More female patients and patients with acute coronary syndrome (ACS) were noted in patients with plaque progression compare to those with no progression (41.9% vs. 18.4%, P < 0.05 and 77.4% vs. 46.3%, P < 0.01, respectively). The serum hs-CRP level also significantly increased in group with plaque progression (0.26 ± 0.44 mg / L vs. 0.02 ± 0.14 mg / L, P < 0.01). Multivariable logistic regression analysis revealed that serum hs-CRP concentration and ACS were independent risk factors of coronary atherosclerotic plaque progression (OR: 12.63,95% CI:1.45-110.29, P < 0.05 and OR:2.99,95% CI:1.04-8.63, P < 0.05, respectively). The frequencies of 6A / 6A genotype and 6A allele of MMP-3 promoter at location -1612 were significantly higher in group with plaque progression than that in group with

  3. Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Ben Lacey, FFPH

    2018-06-01

    Full Text Available Summary: Background: The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage. We aimed to investigate this relationship among adults in China. Methods: 512 891 adults (59% women aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual systolic blood pressure. Findings: During a median follow-up of 9 years (IQR 8–10, there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging. At ages 40–79 years (mean age at event 64 years [SD 9], usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34] and ischaemic stroke (1·30 [1·29–1·31], but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]. HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident

  4. Vascular pattern formation in plants.

    Science.gov (United States)

    Scarpella, Enrico; Helariutta, Ykä

    2010-01-01

    Reticulate tissue systems exist in most multicellular organisms, and the principles underlying the formation of cellular networks have fascinated philosophers, mathematicians, and biologists for centuries. In particular, the beautiful and varied arrangements of vascular tissues in plants have intrigued mankind since antiquity, yet the organizing signals have remained elusive. Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular cells are aligned with one another along continuous lines, and vascular tissues differentiate at reproducible positions within organ environments. However, neither the precise path of vascular differentiation nor the exact geometry of vascular networks is fixed or immutable. Several recent advances converge to reconcile the seemingly conflicting predictability and plasticity of vascular tissue patterns. A control mechanism in which an apical-basal flow of signal establishes a basic coordinate system for body axis formation and vascular strand differentiation, and in which a superimposed level of radial organizing cues elaborates cell patterns, would generate a reproducible tissue configuration in the context of an underlying robust, self-organizing structure, and account for the simultaneous regularity and flexibility of vascular tissue patterns. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Phosphate and Cardiovascular Disease beyond Chronic Kidney Disease and Vascular Calcification

    Directory of Open Access Journals (Sweden)

    Sinee Disthabanchong

    2018-01-01

    Full Text Available Phosphate is essential for life but its accumulation can be detrimental. In end-stage renal disease, widespread vascular calcification occurs as a result of chronic phosphate load. The accumulation of phosphate is likely to occur long before the rise in serum phosphate above the normal range since several observational studies in both general population and early-stage CKD patients have identified the relationship between high-normal serum phosphate and adverse cardiovascular outcomes. Consumption of food high in phosphate increases both fasting and postprandial serum phosphate and habitual intake of high phosphate diet is associated with aging, cardiac hypertrophy, endothelial dysfunction, and subclinical atherosclerosis. The decline in renal function and dietary phosphate load can increase circulating fibroblast growth factor-23 (FGF-23 which may have a direct impact on cardiomyocytes. Increased FGF-23 levels in both CKD and general populations are associated with left ventricular hypertrophy, congestive heart failure, atrial fibrillation, and mortality. Increased extracellular phosphate directly affects endothelial cells causing cell apoptosis and vascular smooth muscle cells (VSMCs causing transformation to osteogenic phenotype. Excess of calcium and phosphate in the circulation can promote the formation of protein-mineral complex called calciprotein particles (CPPs. In CKD, these CPPs contain less calcification inhibitors, induce inflammation, and promote VSMC calcification.

  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. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

  8. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

  9. Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

    Science.gov (United States)

    Hansen, Peter Riis

    2018-01-01

    Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Intrastriatal convection-enhanced delivery results in widespread perivascular distribution in a pre-clinical model

    Directory of Open Access Journals (Sweden)

    Barua Neil U

    2012-01-01

    Full Text Available Abstract Background Convection-enhanced delivery (CED, a direct method for drug delivery to the brain through intraparenchymal microcatheters, is a promising strategy for intracerebral pharmacological therapy. By establishing a pressure gradient at the tip of the catheter, drugs can be delivered in uniform concentration throughout a large volume of interstitial fluid. However, the variables affecting perivascular distribution of drugs delivered by CED are not fully understood. The aim of this study was to determine whether the perivascular distribution of solutes delivered by CED into the striatum of rats is affected by the molecular weight of the infused agent, by co-infusion of vasodilator, alteration of infusion rates or use of a ramping regime. We also wanted to make a preliminary comparison of the distribution of solutes with that of nanoparticles. Methods We analysed the perivascular distribution of 4, 10, 20, 70, 150 kDa fluorescein-labelled dextran and fluorescent nanoparticles at 10 min and 3 h following CED into rat striatum. We investigated the effect of local vasodilatation, slow infusion rates and ramping on the perivascular distribution of solutes. Co-localisation with perivascular basement membranes and vascular endothelial cells was identified by immunohistochemistry. The uptake of infusates by perivascular macrophages was quantified using stereological methods. Results Widespread perivascular distribution and macrophage uptake of fluorescein-labelled dextran was visible 10 min after cessation of CED irrespective of molecular weight. However, a significantly higher proportion of perivascular macrophages had taken up 4, 10 and 20 kDa fluorescein-labelled dextran than 150 kDa dextran (p Conclusions This study suggests that widespread perivascular distribution and interaction with perivascular macrophages is likely to be an inevitable consequence of CED of solutes. The potential consequences of perivascular distribution of

  11. Fabrication and characterization of electrospun poly-L-lactide/gelatin graded tubular scaffolds: Toward a new design for performance enhancement in vascular tissue engineering

    Directory of Open Access Journals (Sweden)

    A. Yazdanpanah

    2015-10-01

    Full Text Available In this study, a new design of graded tubular scaffolds have been developed for the performance enhancement in vascular tissue engineering. The graded poly-L-lactide (PLLA and gelatin fibrous scaffolds produced by electrospining were then characterized. The morphology, degradability, porosity, pore size and mechanical properties of four tubular scaffolds (graded PLLA/gelatin, layered PLLA/gelatin, PLLA and gelatin scaffolds have been investigated. The tensile tests demonstrated that the mechanical strength and also the estimated burst pressure of the graded scaffolds were significantly increased in comparison with the layered and gelatin scaffolds. This new design, resulting in an increase in the mechanical properties, suggested the widespread use of these scaffolds in vascular tissue engineering in order to prepare more strengthened vessels.

  12. Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

    Science.gov (United States)

    Weksler, B B; Tack-Goldman, K; Subramanian, V A; Gay, W A

    1985-02-01

    The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Study of Methionine, Vitamin B12, and Folic Acid Status in Coronary Atherosclerotic Male Patients

    OpenAIRE

    M Djalali; SR A Hoseiny; F Siassi; N Fardad; R Ghiasvand; TR Neyestani

    2007-01-01

    Background: Increased level of serum homocysteine is one of the risk factor of atherosclerosis. Its production related in some sulfur amino acids such as methionine. Some important cofactors that are involved in metabolic pathways of this amino acid are folate and vitamin B12. We have assessed the status of methionine, folic acid, and vitamin B12 in some coronary atherosclerotic male patients.Methods: In this case-control study, 46 cases of coronary atherosclerosis were selected from male pat...

  14. Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Sevostyanova, V. V., E-mail: sevostyanova.victoria@gmail.com; Khodyrevskaya, Y. I.; Glushkova, T. V.; Antonova, L. V.; Kudryavtseva, Y. A.; Barbarash, O. L.; Barbarash, L. S. [Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo (Russian Federation)

    2015-10-27

    The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as a scaffold for tissue-engineered vascular grafts.

  15. Time to foster a rational approach to preventing cardiovascular morbid events.

    Science.gov (United States)

    Cohn, Jay N; Duprez, Daniel A

    2008-07-29

    Efforts to prevent atherosclerotic morbid events have focused primarily on risk factor prevention and intervention. These approaches, based on the statistical association of risk factors with events, have dominated clinical practice in the last generation. Because the cardiovascular abnormalities eventuating in morbid events are detectable in the arteries and heart before the development of symptomatic disease, recent efforts have focused on identifying the presence of these abnormalities as a more sensitive and specific guide to the need for therapy. Advances in noninvasive techniques for studying the vasculature and the left ventricle now provide the opportunity to use early disease rather than risk factors as the tool for clinical decision making. A disease scoring system has been developed using 10 tests of vascular and cardiac function and structure. More extensive data to confirm the sensitivity and specificity of this scoring system and to demonstrate its utility in tracking the response to therapy are needed to justify widespread application in clinical practice.

  16. 64Cu-Labeled LyP-1-Dendrimer for PET-CT Imaging of Atherosclerotic Plaque

    Science.gov (United States)

    2015-01-01

    The ability to detect and quantify macrophage accumulation can provide important diagnostic and prognostic information for atherosclerotic plaque. We have previously shown that LyP-1, a cyclic 9-amino acid peptide, binds to p32 proteins on activated macrophages, facilitating the visualization of atherosclerotic plaque with PET. Yet, the in vivo plaque accumulation of monomeric [18F]FBA-LyP-1 was low (0.31 ± 0.05%ID/g). To increase the avidity of LyP-1 constructs to p32, we synthesized a dendritic form of LyP-1 on solid phase using lysine as the core structural element. Imaging probes (FAM or 6-BAT) were conjugated to a lysine or cysteine on the dendrimer for optical and PET studies. The N-terminus of the dendrimer was further modified with an aminooxy group in order to conjugate LyP-1 and ARAL peptides bearing a ketone. Oxime ligation of peptides to both dendrimers resulted in (LyP-1)4- and (ARAL)4-dendrimers with optical (FAM) and PET probes (6-BAT). For PET-CT studies, (LyP-1)4- and (ARAL)4-dendrimer-6-BAT were labeled with 64Cu (t1/2 = 12.7 h) and intravenously injected into the atherosclerotic (ApoE–/–) mice. After two hours of circulation, PET-CT coregistered images demonstrated greater uptake of the (LyP-1)4-dendrimer-64Cu than the (ARAL)4-dendrimer-64Cu in the aortic root and descending aorta. Ex vivo images and the biodistribution acquired at three hours after injection also demonstrated a significantly higher uptake of the (LyP-1)4-dendrimer-64Cu (1.1 ± 0.26%ID/g) than the (ARAL)4-dendrimer-64Cu (0.22 ± 0.05%ID/g) in the aorta. Similarly, subcutaneous injection of the LyP-1-dendrimeric carriers resulted in preferential accumulation in plaque-containing regions over 24 h. In the same model system, ex vivo fluorescence images within aortic plaque depict an increased accumulation and penetration of the (LyP-1)4-dendrimer-FAM as compared to the (ARAL)4-dendrimer-FAM. Taken together, the results suggest that the (LyP-1)4-dendrimer can be applied for in

  17. Lower limb atherosclerotic disease causes various deteriorations of patients' health-related quality of life.

    Science.gov (United States)

    Koivunen, Kirsi; Lukkarinen, Hannele

    2006-12-01

    Lower limb atherosclerotic disease (LLAD) is a worldwide health problem. Approximately 100,000 Finns have LLAD. Currently, a large number of health-related quality of life (HRQoL) studies are available, but we still have scant comprehensive information of HRQoL of patients with LLAD. The aim was to describe the HRQoL of women and men with LLAD in relation to the age- and sex-matched general population. In addition, the purpose was to study which demographic and relevant clinical and psychologic factors are connected with HRQoL of patients with LLAD. Patients with LLAD (N = 180, 62 women and 118 men) were recruited to participate in this study in the Clinic of Surgery, Oulu University Hospital, from 2001 to 2004. The control sample consisted of an age- and sex-matched general population (N = 2126; 1081 women and 1045 men). The HRQoL of the women and men with LLAD was evaluated using the Nottingham Health Profile (NHP) instrument, in relation to an age- and sex-matched general population (N = 2126) as well as demographic and relevant clinical and psychologic factors. The HRQoL of men was significantly (P women with LLAD was only significantly poorer (P women. The most emphasized relationships between poor HRQoL and the demographic, relevant clinical and psychologic factors were male sex, lack of exercise, retirement, a short painless walking distance, other atherosclerotic disease, poor subjective health status, problems with ability to cope at home, problems with the treatment of illness, and sex life. Male patients with LLAD had poorer HRQoL than the corresponding female patients on the dimensions of energy (P = .023), emotional reaction (P = .050), social isolation (P = .028), and NHP total score (P = .023). Those who did not exercise regularly had poorer HRQoL on the dimensions of energy (P = .005), pain (P = .049), emotional reaction (P = .007), social isolation (P = .001), and physical mobility (P = .028) than those who did exercise regularly. The HRQoL of

  18. Acute non-atherosclerotic ST-segment elevation myocardial infarction in an adolescent with concurrent hemoglobin H-Constant Spring disease and polycythemia vera

    Directory of Open Access Journals (Sweden)

    Ekarat Rattarittamrong

    2015-09-01

    Full Text Available Thrombosis is a major complication of polycythemia vera (PV and also a well-known complication of thalassemia. We reported a case of non-atherosclerotic ST-segment elevation myocardial infarction (STEMI in a 17- year-old man with concurrent post-splenectomized hemoglobin H-Constant Spring disease and JAK2 V617F mutation-positive PV. The patient initially presented with extreme thrombocytosis (platelet counts greater than 1,000,000/μL and three months later developed an acute STEMI. Coronary artery angiography revealed an acute clot in the right coronary artery without atherosclerotic plaque. He was treated with plateletpheresis, hydroxyurea and antiplatelet agents. The platelet count decreased and his symptoms improved. This case represents the importance of early diagnosis, awareness of the increased risk for thrombotic complications, and early treatment of PV in patients who have underlying thalassemia with marked thrombocytosis.

  19. Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael D. Shapiro

    2017-02-01

    Full Text Available Cholesterol-rich, apolipoprotein B (apoB-containing lipoproteins are now widely accepted as the most important causal agents of atherosclerotic cardiovascular disease. Multiple unequivocal and orthogonal lines of evidence all converge on low-density lipoprotein and related particles as being the principal actors in the genesis of atherosclerosis. Here, we review the fundamental role of atherogenic apoB-containing lipoproteins in cardiovascular disease and several other humoral and parietal factors that are required to initiate and maintain arterial degeneration. The biology of foam cells and their interactions with high-density lipoproteins, including cholesterol efflux, are also briefly reviewed.

  20. The impact of splenectomy on human coronary artery atherosclerosis and vascular macrophage distribution.

    Science.gov (United States)

    Li, Yu; Stone, James R

    Splenectomy can potentially impact atherosclerosis through multiple mechanisms including altered lipid homeostasis, increased coagulation, and altered macrophage recruitment to the plaque. In patients, splenectomy has been associated with increased rates of coronary artery events, while in experimental mice, splenectomy causes increased atherosclerosis but reduces systemic monocyte supply. In this study, the direct impact of splenectomy on human coronary artery atherosclerotic plaque severity and macrophage content was investigated. Coronary artery atherosclerotic plaque severity was determined at autopsy in 18 long-term (≥10 years) splenectomy patients and 90 matched control patients. Coronary artery macrophage content was evaluated in mild atherosclerotic plaques of 11 mid- to long-term (≥1 year) splenectomy patients and 11 matched control patients. Splenectomy was associated with reduced coronary artery atherosclerosis (P=.03). The association was most pronounced for the subgroup of patients who had undergone splenectomy 20 years or more prior to death (P=.02). There was no difference in the density of macrophages in the plaque, media, or adventitia upon comparing splenectomy and control patients. In the control group, there was no correlation between the macrophage densities in the three arterial layers. However, in the splenectomy patients, there was a strong correlation in the macrophage densities across the plaque, media, and adventitia (P≤.0002), with resulting slopes that were significantly greater than seen in the control patients (P=.0007-.011). These findings indicate that, in humans, splenectomy is associated with lower coronary artery atherosclerotic plaque severity and altered coronary artery macrophage distribution. These results suggest that the spleen can modulate the recruitment of macrophages into human coronary arteries and the progression of atherosclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Antiplatelet therapy and vascular disease: an update.

    Science.gov (United States)

    Buch, Mamta H; Prendergast, Bernard D; Storey, Robert F

    2010-08-01

    Atherosclerosis is a diffuse, systemic disorder of the large and medium-sized arterial vessels, affecting the coronary, cerebral and peripheral circulation. Chronic inflammatory processes are the central pathophysiological mechanism largely driven by lipid accumulation, and provide the substrate for occlusive thrombus formation. The clinical sequelae of acute arterial thrombosis, heart attack and stroke, are the most common causes of morbidity and mortality in the industrialized world. Such acute events are characterized by rupture or erosion of the atherosclerotic plaque leading to acute thrombosis. The atherosclerotic process and associated thrombotic complications are collectively termed atherothrombosis. The platelet is a pivotal mediator of various endothelial, immune, thrombotic and inflammatory responses and therefore a key player in the initiation and progression of atherothrombosis. A robust evidence base supports the clear clinical benefits of antiplatelet agents in the primary and secondary therapy of atherothrombotic disorders. Percutaneous coronary and peripheral interventions have an established central role in the management of atherothrombotic disease and demand a greater understanding of platelet biology. In this article, we provide a clinically orientated overview of the pathophysiology of arterial thrombosis and the evidence supporting the use of the various established antiplatelet therapies, and discuss new and future agents.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

    topics have been investigated: an ultrasound pulse-echo simulation tool and a new compound imaging technique for improving visualization of atherosclerotic disease.A tool for simulation of the received electrical signal in a pulse-echo ultrasound system, due to a reflector surface of arbitrary geometry......, has been developed. The method is denoted the Diffraction Response Interpolation Method (DRIM) and is based on the pulse-echo diffraction impulse response method. The DRIM is a computationally efficient tool for calculating the integral of the spatially varying pulse-echo diffraction impulse response...... definition of the interfaces in the cases where one or more of the beams had near-normal incidence on the interface, i.e. an improved visualization over an angular range of interface orientations roughly corresponding to the range of beam angles used. The speckle statistics and the speckle reduction have...

  4. Lipid and protein maps defining arterial layers in atherosclerotic aorta

    Directory of Open Access Journals (Sweden)

    Marta Martin-Lorenzo

    2015-09-01

    Full Text Available Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to identify ongoing molecular changes in atherosclerosis development. Mass Spectrometry Imaging (MSI accounts with the unique advantage of analyzing proteins and metabolites (lipids while preserving their original localization; thus two dimensional maps can be obtained. Main molecular alterations were investigated in a rabbit model in response to early development of atherosclerosis. Aortic arterial layers (intima and media and calcified regions were investigated in detail by MALDI-MSI and proteins and lipids specifically defining those areas of interest were identified. These data further complement main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J. Proteomics. (In press; M. Martin-Lorenzo et al., J. Proteomics 108 (2014 465–468. [1,2].

  5. Double-filter identification of vascular-expressed genes using Arabidopsis plants with vascular hypertrophy and hypotrophy.

    Science.gov (United States)

    Ckurshumova, Wenzislava; Scarpella, Enrico; Goldstein, Rochelle S; Berleth, Thomas

    2011-08-01

    Genes expressed in vascular tissues have been identified by several strategies, usually with a focus on mature vascular cells. In this study, we explored the possibility of using two opposite types of altered tissue compositions in combination with a double-filter selection to identify genes with a high probability of vascular expression in early organ primordia. Specifically, we generated full-transcriptome microarray profiles of plants with (a) genetically strongly reduced and (b) pharmacologically vastly increased vascular tissues and identified a reproducible cohort of 158 transcripts that fulfilled the dual requirement of being underrepresented in (a) and overrepresented in (b). In order to assess the predictive value of our identification scheme for vascular gene expression, we determined the expression patterns of genes in two unbiased subsamples. First, we assessed the expression patterns of all twenty annotated transcription factor genes from the cohort of 158 genes and found that seventeen of the twenty genes were preferentially expressed in leaf vascular cells. Remarkably, fifteen of these seventeen vascular genes were clearly expressed already very early in leaf vein development. Twelve genes with published leaf expression patterns served as a second subsample to monitor the representation of vascular genes in our cohort. Of those twelve genes, eleven were preferentially expressed in leaf vascular tissues. Based on these results we propose that our compendium of 158 genes represents a sample that is highly enriched for genes expressed in vascular tissues and that our approach is particularly suited to detect genes expressed in vascular cell lineages at early stages of their inception. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-10-05

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-03-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  9. Proatherogenic pathways leading to vascular calcification

    International Nuclear Information System (INIS)

    Mazzini, Michael J.; Schulze, P. Christian

    2006-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease

  10. Are neonicotinoid insecticides driving declines of widespread butterflies?

    Directory of Open Access Journals (Sweden)

    Andre S. Gilburn

    2015-11-01

    Full Text Available There has been widespread concern that neonicotinoid pesticides may be adversely impacting wild and managed bees for some years, but recently attention has shifted to examining broader effects they may be having on biodiversity. For example in the Netherlands, declines in insectivorous birds are positively associated with levels of neonicotinoid pollution in surface water. In England, the total abundance of widespread butterfly species declined by 58% on farmed land between 2000 and 2009 despite both a doubling in conservation spending in the UK, and predictions that climate change should benefit most species. Here we build models of the UK population indices from 1985 to 2012 for 17 widespread butterfly species that commonly occur at farmland sites. Of the factors we tested, three correlated significantly with butterfly populations. Summer temperature and the index for a species the previous year are both positively associated with butterfly indices. By contrast, the number of hectares of farmland where neonicotinoid pesticides are used is negatively associated with butterfly indices. Indices for 15 of the 17 species show negative associations with neonicotinoid usage. The declines in butterflies have largely occurred in England, where neonicotinoid usage is at its highest. In Scotland, where neonicotinoid usage is comparatively low, butterfly numbers are stable. Further research is needed urgently to show whether there is a causal link between neonicotinoid usage and the decline of widespread butterflies or whether it simply represents a proxy for other environmental factors associated with intensive agriculture.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  12. Smoking Cessation Counseling Improves Quality of Care and Surgical Outcomes with Financial Gain for a Vascular Practice.

    Science.gov (United States)

    Moses, D A; Mehaffey, J H; Strider, D V; Tracci, M C; Kern, J A; Upchurch, G R

    2017-07-01

    Cigarette smoking is strongly associated with atherosclerotic disease. It is incumbent on vascular surgeons to provide smoking cessation counseling (SCC) to their patients. The objective of this study was to determine the association of SCC and improvement in quality of care. As a quality project using retrospective data, the study received institutional review board exemption status. A retrospective review of prospectively maintained database from April 2014 through March 2015 of outpatient encounters in a vascular surgery clinic was performed of current smokers. Through the quality support team, providers were encouraged to counsel smokers to quit, document the discussion, and bill specific Evaluate and Management codes (99406 and 99407). The number of outpatients by smoking status, documentation and billing of SCC, demographics of current smokers, and monetary collections were collected. Data were compared using a correlation coefficient calculated and tested for statistical significant using two-tailed t-test. A sample of 1,077 visits by 612 currently smoking patients accounted for 24% of all outpatient vascular surgery visits. The average age was 61 years, and 64% were male. Comorbidities included 77% with hypertension, 32% with diabetes mellitus, and 14% with chronic kidney disease. Medically, 72% were on aspirin, 71% on statin, and 48% on beta blocker. A total of 208 (34%) never underwent a vascular intervention, and 183 (30%) had an intervention during the study period (44% for peripheral artery disease, 10% for carotid stenosis, 14% amputations, and 10% abdominal aortic aneurysm). Documentation improved from 65% of encounters during the first month to 89% in the peak month and 79% of total encounters. All-cause mortality rate was 2%, and this cohort demonstrated 75% SCC for 28 encounters. Fifty-five patients (9%) quit smoking for more than 30 days at the end of the study period, and this cohort had 69% of their 97 encounters with documented SCC

  13. Gas solubilities widespread applications

    CERN Document Server

    Gerrard, William

    1980-01-01

    Gas Solubilities: Widespread Applications discusses several topics concerning the various applications of gas solubilities. The first chapter of the book reviews Henr's law, while the second chapter covers the effect of temperature on gas solubility. The third chapter discusses the various gases used by Horiuti, and the following chapters evaluate the data on sulfur dioxide, chlorine data, and solubility data for hydrogen sulfide. Chapter 7 concerns itself with solubility of radon, thoron, and actinon. Chapter 8 tackles the solubilities of diborane and the gaseous hydrides of groups IV, V, and

  14. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  15. Verapamil stereoisomers induce antiproliferative effects in vascular smooth muscle cells via autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Salabei, Joshua K. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40202 (United States); Balakumaran, Arun [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Frey, Justin C. [Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54702 (United States); Boor, Paul J. [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Treinen-Moslen, Mary [Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555‐0609 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States); Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Division of Cardiovascular Medicine, University of Louisville, Louisville, KY 40202 (United States); Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54702 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555‐0438 (United States)

    2012-08-01

    Calcium channel blockers (CCBs) are important in the management of hypertension and limit restenosis. Although CCB efficacy could derive from decreased blood pressure, other mechanisms independent of CCB activity also can contribute to antiproliferative action. To understand mechanisms of CCB-mediated antiproliferation, we studied two structurally dissimilar CCBs, diltiazem and verapamil, in cultured rat vascular smooth muscle cells (VSMC). To elucidate CCB-independent effects, pure stereoisomers of verapamil (R-verapamil, inactive VR; S-verapamil, active, VS) were used. The effects of CCB exposure on cell viability (MTT reduction), cell proliferation ({sup 3}H-thymidine incorporation), VSMC morphology by light and transmission electron microscopy (TEM) and autophagy (LC3I/II, ATG5) were measured. In general, verapamil, VR or VS treatment alone (80 μM) appreciably enhanced MTT absorbance although higher concentrations (VR or VS) slightly decreased MTT absorbance. Diltiazem (140 μM) markedly decreased MTT absorbance (40%) at 120 h. VR or VS treatment inhibited {sup 3}H-thymidine incorporation (24 h) and induced cytological alterations (i.e., karyokinesis, enhanced perinuclear MTT deposition, accumulated perinuclear “vacuoles”). TEM revealed perinuclear “vacuoles” to be aggregates of highly laminated and electron-dense vesicles resembling autophagosomes and lysosomes, respectively. Increased autophagosome activity was confirmed by a concentration-dependent increase in LC3-II formation by Western blotting and by increased perinuclear LC3-GFP{sup +} puncta in verapamil-treated VSMC. Verapamil stereoisomers appeared to decrease perinuclear mitochondrial density. These observations indicate that antiproliferative effects of verapamil stereoisomers are produced by enhanced mitochondrial damage and upregulated autophagy in VSMC. These effects are independent of CCB activity indicating a distinct mechanism of action that could be targeted for more efficacious anti-atherosclerotic

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

    Science.gov (United States)

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

    2017-06-01

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

  17. [18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs.

    Directory of Open Access Journals (Sweden)

    Miikka Tarkia

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

  18. Prevalence, Impact, and Predictive Value of Detecting Subclinical Coronary and Carotid Atherosclerosis in Asymptomatic Adults

    DEFF Research Database (Denmark)

    Baber, Usman; Mehran, Roxana; Sartori, Samantha

    2015-01-01

    BACKGROUND: Although recent studies suggest that measuring coronary artery calcification (CAC) may be superior to indirect atherosclerotic markers in predicting cardiac risk, there are limited data evaluating imaging-based biomarkers that directly quantify atherosclerosis in different vascular beds...

  19. Thermal Non-equilibrium Consistent with Widespread Cooling

    Science.gov (United States)

    Winebarger, A.; Lionello, R.; Mikic, Z.; Linker, J.; Mok, Y.

    2014-01-01

    Time correlation analysis has been used to show widespread cooling in the solar corona; this cooling has been interpreted as a result of impulsive (nanoflare) heating. In this work, we investigate wide-spread cooling using a 3D model for a solar active region which has been heated with highly stratified heating. This type of heating drives thermal non-equilibrium solutions, meaning that though the heating is effectively steady, the density and temperature in the solution are not. We simulate the expected observations in narrowband EUV images and apply the time correlation analysis. We find that the results of this analysis are qualitatively similar to the observed data. We discuss additional diagnostics that may be applied to differentiate between these two heating scenarios.

  20. Emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries

    International Nuclear Information System (INIS)

    Chen, Wengen; Bural, Gonca G.; Torigian, Drew A.; Alavi, Abass; Rader, Daniel J.

    2009-01-01

    Atherosclerosis is a dynamic inflammatory disorder. The biological composition and inflammatory state of an atherosclerotic plaque, rather than the degree of stenosis or its size are the major determinants of acute clinical events. A noninvasive technique to detect vulnerable atherosclerotic plaque is critically needed. FDG-PET/CT, a combined functional and structural whole-body imaging modality, holds great potential for this purpose. FDG uptake in large arteries has been frequently observed and is associated with cardiovascular risk factors. FDG accumulates in plaque macrophages and uptake is correlated with macrophage density. It is known that vascular FDG uptake and calcification do not overlap significantly and changes of FDG uptake are common, suggesting that FDG uptake may represent a dynamic inflammatory process. It has been reported that vascular FDG uptake can be attenuated by simvastatin in patients, and by the antiinflammatory drug probucol in rabbits. Vascular FDG uptake has been linked to cardiovascular events in some preliminary studies. Data from basic sciences, and animal and clinical studies support the emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries in humans. (orig.)

  1. Antioxidants attenuate atherosclerotic plaque development in a balloon-denuded and -radiated hypercholesterolemic rabbit

    International Nuclear Information System (INIS)

    Leborgne, Laurent; Fournadjiev, Jana; Pakala, Rajbabu; Dilcher, Christian; Cheneau, Edouard; Wolfram, Roswitha; Hellinga, David; Seaborn, Rufus; O'Tio, Fermin; Waksman, Ron

    2003-01-01

    Background: Oxidation of lipoproteins is considered to be a key contributor to atherogenesis. Antioxidants are potential antiatherogenic agents because they can inhibit lipoprotein oxidation. Radiation has been shown to increase oxidative stress leading to increased atherogenesis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and -radiated rabbits. Methods and Results: Two groups of New Zealand white rabbits (n=36) were fed with 1% cholesterol diet (control diet) or with 1% cholesterol diet containing a mixture of various antioxidants for 1 week. Iliac arteries in all the animals were balloon denuded and continued to fed with 0.15% cholesterol diet or 0.15% cholesterol diet containing antioxidants (antioxidant diet). Four weeks after balloon denudation one iliac artery in 12 animals from each group was radiated and all the animals were continued to be fed with the same diet. Four weeks after radiation animals were sacrificed and morphometric analysis of iliac arteries (n=12) in nonradiated and radiated animals were performed. Plaque area (PA) in the rabbits that were fed with cholesterol diet is 0.2±0.12 mm 2 , and it is increased by 2.75-fold (P<.05) in the radiated arteries of animals fed with cholesterol diet. Plaque area in the animals fed with antioxidant diet is 50% less then the one in the animals fed with cholesterol diet. Similarly, plaque area in radiated arteries of the animals fed with antioxidant diet is 50% less then the animals fed with cholesterol diet. Conclusion: Antioxidants significantly attenuate atherosclerotic plaque progression in balloon-injured and -radiated hypercholesterolemic rabbits

  2. Prevalence of hereditary haemochromatosis in premature atherosclerotic vascular disease

    NARCIS (Netherlands)

    Franco, R. F.; Zago, M. A.; Trip, M. D.; ten Cate, H.; van den Ende, A.; Prins, M. H.; Kastelein, J. J.; Reitsma, P. H.

    1998-01-01

    It has been proposed that iron accumulation may contribute to atherogenesis by increasing free radical formation and oxidative stress. Epidemiological studies in which the association of iron status with atherosclerosis was assessed raised conflicting results. To test whether genetic

  3. Vascular injuries of the upper extremity Lesões vasculares de membros superiores

    Directory of Open Access Journals (Sweden)

    Raafat Shalabi

    2006-12-01

    Full Text Available OBJECTIVE: This study analyzes the causes of injuries, presentations, surgical approaches, outcome and complications of vascular trauma of the upper limbs, in spite of limited hospital resources. METHODS: A 5-year retrospective analysis. From 01/01/2001 to 31/12/2005, 165 patients were operated for vascular injuries at King Fahd Hospital, Medina, Saudi Arabia. Of all peripheral vascular trauma patients (115, upper limb trauma was present in 58. Diagnosis was made by physical examination and hand-held Doppler alone or in combination with Doppler scan/angiography. Primary vascular repair was performed whenever possible; otherwise, the interposition vein graft was used. Fasciotomy was considered when required. Patients with unsalvageable lower extremity injury requiring primary amputation were excluded from the study. RESULTS: Fifty patients were male (86% and eight were female (14%, aged between 2.5-55 years (mean 23 years. Mean duration of presentation was 8 h after the injury. The most common etiological factor was road traffic accidents, accounting for 50.5% in the blunt trauma group and 33% among all penetrating and stab wound injuries. Incidence of concomitant orthopedic injuries was very high in our study (51%. The brachial artery was the most affected (51%. Interposition vein grafts were used in 53% of the cases. Limb salvage rate was 100%. CONCLUSION: Patients who suffer vascular injuries of the upper extremities should be transferred to vascular surgery centers as soon as possible. Decisive management of peripheral vascular trauma will maximize patient survival and limb salvage. Priorities must be established in the management of associated injuries, and delay must be avoided when ischemic changes are present.OBJETIVO: Este estudo analisa as causas de lesões, apresentação, abordagens cirúrgicas, desfechos e complicações do trauma vascular de membros superiores, apesar de recursos hospitalares limitados. MÉTODOS: An

  4. Is type 2 diabetes mellitus a vascular disease (atheroscleropathy with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress.

    Directory of Open Access Journals (Sweden)

    Tyagi Suresh C

    2003-02-01

    Full Text Available Abstract Background Cardiovascular disease accounts for at least 85 percent of deaths for those patients with type 2 diabetes mellitus (T2DM. Additionally, 75 percent of these deaths are due to ischemic heart disease. Hypothesis Is type 2 diabetes mellitus a vascular disease (atheroscleropathy with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress. Testing of the hypothesis The vulnerable three arms of the eNOS reaction responsible for the generation of eNO is discussed in relation to the hypothesis: (1. The L-arginine substrate. (2. The eNOS enzyme. (3. The BH4 cofactor. Implications of the hypothesis If we view T2DM as a vascular disease initially with a later manifestation of hyperglycemia, we may be able to better understand and modify the multiple toxicities associated with insulin resistance, metabolic syndrome, prediabetes, overt T2DM, and accelerated atherosclerosis (atheroscleropathy. The importance of endothelial nitric oxide synthase, endothelial nitric oxide, tetrahydrobiopterin (BH4, L-arginine, and redox stress are discussed in relation to endothelial cell dysfunction and the development and progression of atheroscleropathy and T2DM. In addition to the standard therapies to restore endothelial cell dysfunction and stabilization of vulnerable atherosclerotic plaques, this article will discuss the importance of folic acid (5MTHF supplementation in this complex devastating disease process. Atheroscleropathy and hyperglycemia could be early and late manifestations, respectively, in the natural progressive history of T2DM.

  5. Pediatric central nervous system vascular malformations

    Energy Technology Data Exchange (ETDEWEB)

    Burch, Ezra A. [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Orbach, Darren B. [Boston Children' s Hospital, Neurointerventional Radiology, Boston, MA (United States)

    2015-09-15

    Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations. (orig.)

  6. Pediatric central nervous system vascular malformations

    International Nuclear Information System (INIS)

    Burch, Ezra A.; Orbach, Darren B.

    2015-01-01

    Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations. (orig.)

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  8. Stent-assisted recanalization of atherosclerotic intracranial stenosis

    International Nuclear Information System (INIS)

    Soo Mee Lim; Dae Chul Suh

    2006-01-01

    Intracranial atherosclerosis is a major cause of ischemic stroke, and depending on the studied population, it accounts for 8%-15% of all strokes that are due to cerebral atherosclerosis. The prognosis of patients with symptomatic intracranial stenoses seems to depend on the location and extent of intracranial atherosclerosis. Currently, the primary treatment in intracranial atherosclerosis is the control of vascular risk factors such as hypertension, diabetes, hypercholesterolemia, and smoking. Secondary prevention with antiplatelet therapy has been shown to reduce the risk of subsequent vascular events in patients who have suffered a recent ischemic stroke or transient ischemic attack (TIA). Unfortunately, a significant number of patients with intracranial atherosclerosis continue to suffer from repeated strokes or TIA despite maximal medical treatment. Although endovascular revascularization for symptomatic intracranial stenoses remains at the investigational stage and much of the pertinent information is anecdotal, intracranial angioplasty and stenting are being increasingly performed to treat stenotic lesions. This article reviews basic principles involved in the patient selection, premedication, angio-interventional procedures, angiographic and clinical results, periprocedural complication, patients aftercare. (authors)

  9. 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...... deviation and autocorrelation) provide good correlation within the training set (p = 0.04); However, the correlation found so far is not so high, that the method can be used in clinical prediction of plaque constituents....

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

    Science.gov (United States)

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

    2017-01-01

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

  11. Irbesartan increased PPARγ activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

    International Nuclear Information System (INIS)

    Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

    2011-01-01

    Research highlights: → Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. → Irbesartan decreased white adipose tissue weight without affecting body weight. → DNA-binding for PPARγ was increased in white adipose tissue in vivo by irbesartan. → Irbesartan increased adipocyte number in white adipose tissue. → Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPARγ agonistic action of an AT 1 receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPARγ in white adipose tissue and the DNA-binding activity of PPARγ in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPARγ and improved adipose tissue dysfunction including insulin resistance.

  12. Penile gangrene in diabetes mellitus with renal failure: A poor prognostic sign of systemic vascular calciphylaxis

    Directory of Open Access Journals (Sweden)

    Mayank Mohan Agarwal

    2007-01-01

    Full Text Available Penile gangrene associated with chronic renal failure is very uncommon. A 52-year-old man with diabetes mellitus, diffuse atherosclerosis, ischemic cardiomyopathy and end-stage renal disease presented with blackening of distal penis for 10 days. His general condition was poor and gangrene of prepuce and glans was noted. Doppler and magnetic-resonance angiography revealed bilateral internal iliac artery obstruction. He underwent trocar suprapubic cystostomy and was planned for partial penectomy. But he died of severe diabetic complications in the interim period. Penile gangrene is a manifestation of widespread vascular calcifications associated with end-stage renal disease and is a marker of poor prognosis.

  13. Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

    Science.gov (United States)

    Fisher, Mark

    2008-01-01

    Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

  14. The Veterans Affairs Cardiac Risk Score: Recalibrating the Atherosclerotic Cardiovascular Disease Score for Applied Use.

    Science.gov (United States)

    Sussman, Jeremy B; Wiitala, Wyndy L; Zawistowski, Matthew; Hofer, Timothy P; Bentley, Douglas; Hayward, Rodney A

    2017-09-01

    Accurately estimating cardiovascular risk is fundamental to good decision-making in cardiovascular disease (CVD) prevention, but risk scores developed in one population often perform poorly in dissimilar populations. We sought to examine whether a large integrated health system can use their electronic health data to better predict individual patients' risk of developing CVD. We created a cohort using all patients ages 45-80 who used Department of Veterans Affairs (VA) ambulatory care services in 2006 with no history of CVD, heart failure, or loop diuretics. Our outcome variable was new-onset CVD in 2007-2011. We then developed a series of recalibrated scores, including a fully refit "VA Risk Score-CVD (VARS-CVD)." We tested the different scores using standard measures of prediction quality. For the 1,512,092 patients in the study, the Atherosclerotic cardiovascular disease risk score had similar discrimination as the VARS-CVD (c-statistic of 0.66 in men and 0.73 in women), but the Atherosclerotic cardiovascular disease model had poor calibration, predicting 63% more events than observed. Calibration was excellent in the fully recalibrated VARS-CVD tool, but simpler techniques tested proved less reliable. We found that local electronic health record data can be used to estimate CVD better than an established risk score based on research populations. Recalibration improved estimates dramatically, and the type of recalibration was important. Such tools can also easily be integrated into health system's electronic health record and can be more readily updated.

  15. Vascular malformations in pediatrics

    International Nuclear Information System (INIS)

    Reith, W.; Shamdeen, M.G.

    2003-01-01

    Vascular malformations are the cause of nearly all non-traumatic intracranial hemorrhage in children beyond the neonatal stage. Therefore, any child presenting with spontaneous intracranial hemorrhage should be evaluated for child abuse and for vascular malformations. Intracerebral malformations of the cerebral vasculature include vein of Galen malformations, arteriovenous malformation (AVM), cavernomas, dural arteriovenous fistulas, venous anomalies (DVA), and capillary teleangiectasies. Although a few familial vascular malformation have been reported, the majority are sporadic. Clinical symptoms, diagnostic and therapeutic options are discussed. (orig.) [de

  16. In vitro Spatial Compound Scanning for Improved Visualization of Atherosclerosis

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh; Wilhjelm, Jens E.; Sillesen, Henrik

    2000-01-01

    A new off-line multiangle ultrasound (US) compound scanner has been built with the purpose of investigating possible improvements in visualization of vascular structure. Images of two formalin-fixed human atherosclerotic plaques removed by carotid endarterectomy were recorded from seven insonific...

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

    Science.gov (United States)

    Kawai, Yoshichika

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-10

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

  20. Contemporary vascular smartphone medical applications.

    Science.gov (United States)

    Carter, Thomas; O'Neill, Stephen; Johns, Neil; Brady, Richard R W

    2013-08-01

    Use of smartphones and medical mHealth applications (apps) within the clinical environment provides a potential means for delivering elements of vascular care. This article reviews the contemporary availability of apps specifically themed to major vascular diseases and the opportunities and concerns regarding their integration into practice. Smartphone apps relating to major vascular diseases were identified from the app stores for the 6 most popular smartphone platforms, including iPhone, Android, Blackberry, Nokia, Windows, and Samsung. Search terms included peripheral artery (arterial) disease, varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers, hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic disorders. Forty-nine vascular-themed apps were identified. Sixteen (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings, but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical professional involvement in their design or content. The integration of apps into the delivery of care has the potential to benefit vascular health care workers and patients. However, high-quality apps designed by clinicians with vascular expertise are currently lacking and represent an area of concern in the mHealth market. Improvement in the quality and reliability of these apps will require the development of robust regulation. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

    Science.gov (United States)

    Atchison, Elizabeth A; Garrity, James A; Castillo, Francisco; Engman, Steven J; Couch, Steven M; Salomão, Diva R

    2016-01-01

    Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. A total of 52 patients who underwent removal of vascular orbital lesions. The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). The existence and pattern of staining with VEGF and its subtypes on these lesions. There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. A