... Because the mechanisms leading to the development of restenosis are likely different from those that produce primary atherosclerosis, a comparison of the pathophysiology of (J Vasc Surg 2009;49:1289-95.) Monocytes inhibit SMC proliferation [93] Human ASMC, Monocytes . SMC proliferation Myocytes were seeded at a density of 5 X 10 4 per 35-mm dish (human) or 2 X 10 5 per 35-mm dish (rat) and incubated with MEM supplemented with 10% fetal calf serum; 24 h later, the medium was replaced with one containing 0.4% fetal calf serum to stop cell growth, and the cultures were incubated for 72 h. Cell proliferation SMC proliferation makes an important contribu-tion to the growth of the atherosclerotic plaque, and type I collagen is a critical regulator of prolifer-ation. Considerable in vivo studies support the role of free radical reactions in atherogenesis and atherosclerotic‐related coronary heart disease. Atherosclerosis is a chronic, progressive lipid driven inflammatory disease. Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. Factors releasedÆSMC recruitment 6. Static - Direct or Indirect - Transwell The low-density lipoprotein receptor–related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). Here we report that let-7 levels are decreased in diabetic human carotid plaques and in a model of diabetes-associated atherosclerosis… Atherosclerosis involves multiple processes including endothelial dysfunction, inflammation, vascular proliferation and matrix alteration. Models of atherosclerosis consist of combinations of: Endothelial Cells (EC), Smooth Muscle Cells (SMC) and … To confirm a role for Smad3 in SMC proliferation, we both upregulated Smad3 via adenoviral mediated gene transfer (AdSmad3) and inhibited Smad3 through transfection with siRNA in human aortic SMCs, then assessed cell proliferation with tritiated thymidine. Knockout of the Murine Ortholog to the Human 9p21 Coronary Artery Disease Locus Leads to SMC Proliferation, Vascular Calcification, and Advanced Atherosclerosis Yoko Kojima * , Jianqin Ye , Vivek Nanda , Ying Wang , Alyssa M. Flores , Kai-Uwe Jarr , Pavlos Tsantilas , Liang Guo , Aloke V. Finn , Renu Virmani , Nicholas Leeper DISCUSSION Diabetes markedly accelerates SMC proliferation and accumulation in atherosclerotic lesions. Here we show that LRP1 forms a complex with the PDGF receptor (PDGFR). SMC proliferation . Accumulation of lipoproteins (LDL mainly) 3. Overexpression of Smad3 enhanced whereas inhibition of Smad3 decreased cell proliferation. The low-density lipoprotein … Second, SMC proliferation can be inhibited by NO, which is a key component of arterial vessel wall remodeling in response to injury, for example, after angioplasty or vein grafting and during atherosclerosis formation . • SMC proliferation without macrophage foam cell infiltration is frequently observed in BMS implants, especially in those aged <5 years. SMC proliferation and the pathophysiology of restenosis in humans. Progression to full atherosclerotic plaque ensues: Intimal SMC emigration and proliferation continues SMC elaborate collagen which forms fibrous cap Progressive lipid accumulation within cells (macrophages & SMC = foam cells) and extracellularly PROGRESSION OF AORTIC ATHEROSCLEROSIS ATHEROSCLEROTIC PLAQUES: VULNERABLE (UNSTABLE) vs. Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. Platelet adhesion 5. In westernized societies, it is the underlying cause of about 50% of all deaths. Magnier-Gaubil et al. These fatty plaques contain lipid‐laden macrophages that accumulate because of the recruitment of circulating monocytes and local differentiation and proliferation of macrophages 1-4.Atherosclerosis is initiated by endothelial damage induced … Atherosclerosis is a chronic inflammatory response of the artil llt dthlilijterial wall to endothelial injury. Atherosclerosis is a lipid‐driven inflammatory disease characterised by plaque formation in the large arteries. Smooth muscle cell (SMC) proliferation in the arterial wall has been implicated as having a central role in hypertension, atherosclerosis, and restenosis after angioplasty. Therefore, the pathogenesis of atherosclerosis is a result of various changes and interactions in multiple cell types in the artery walls which mainly includes lipid deposition, endothelial cell dysfunction, macrophages activation, and SMC alternation . Hyperlipidemia and other risk factors are thought to cause endothelial injury, resulting in adhesion of platelets and monocytes and release of growth factors, including platelet-derived growth factor (PDGF), which lead to SMC migration and proliferation. Characterization of primary and restenotic atherosclerotic plaque from the superficial femoral artery: Potential role of Smad3 in regulation of SMC proliferation Previous Article Proliferative capacity of vein graft smooth muscle cells and fibroblasts in vitro correlates with graft stenosis Summary. Monocyte adhesion to endothelium 4 Platelet adhesion basic tenets 4. Current in vitro models of atherosclerosis. The majority of cardiovascular diseases are the result of vascular remodeling underlying the development of atherosclerosis and its occlusive complications. The low-density lipoprotein receptor-related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). TNF-α is an important proinflammatory cytokine , which serves a role in atherosclerosis and AAA by stimulating the expression of adhesion molecules and MMPs (31–33). Thus, their dysfunction plays a key role in atherosclerosis. The development of atherosclerosis is a multifactorial process in which both elevated plasma cholesterol levels and proliferation of smooth muscle cells (SMC) play central roles 33. Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. The increase in SMC proliferation is considered an important step in the pathogenesis of atherosclerosis (54, 55). While the central role played by TGFb in regulation of SMC differentiation has been previously demonstrated (Lindner & Reidy, 1991; Hirschi et al, 1998; Kawai-Kowase et al, 2004), little is known about what regulates this pathway and what contribution SMC proliferation makes to progression of lesions seen in atherosclerosis (Tabas et al, 2015). Atherosclerosis is an autoimmune disease caused by self- and non-self-antigens contributing to excessive activation of T and B cell immune responses. Endothelial cells play a key role in nearly every step of the atherosclerosis process, including plaque formation, platelet adhesion and aggregation, cellular migration, and proliferation. 1 In addition to endothelial dysfunction and macrophage-derived inflammation, proliferation of smooth muscle cells (SMC) constitutes an essential component for atherosclerosis formation and neointimal remodeling. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at … Furthermore, TNF-α is involved in activation of the mitogen-activated protein kinase cascade, leading to vascular SMC migration and proliferation (31,32,34). In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. studied the cellular events of quail atherosclerosis using monoclonal antibodies to alpha-actin and chicken macrophages and effectively identified the presence of SMC and macrophages, respectively, as constituents of the atherosclerotic lesions. ... (due to TGF and PDGF released by platelets and thrombin itself causes SMC proliferation and ECM deposition) contributes to leison evolution and plaque growth. The molecular mechanism underlying SMC proliferation, however, is not completely understood. showed that TGF-β inhibits PDGF-stimulated proliferation of SMC. Involves the tunica intima of the arterial wall. Hypothetical sequence of cellular interactions in atherosclerosis. Late phase of atherosclerosis 5th type of lesion (fibroatheroma) – proliferation and expression of secretional phenotype of SMC, synthesis of extracellular matrix (colagen and elastic fibres), the cover = thin layer of smooth muscle cells forming fibrous crust (“cap”) over the atherosclerosis are not well understood. Koyama and colleagues found that plating SMCs on top of polymerized two dimensional (2-D) type I collagen maintained SMC quiescence Most of the current concepts on morphogenesis of atherosclerosis attribute the development of atherosclerotic lesions to the combined effects of two main cellular events: 1) activation of macrophages leading to lipoprotein phagocytosis by scavenger cells, and 2) proliferation of smooth muscle cells (SMC). Both M-CSF and monocyte induced SMC apoptosis requires Mac-1 and ICAM-1 mediated binding of monocyte to SMC [88] Human PBMCs, carotid, coronary medial, and aortic SMC . The effect of TGF-β on the proliferation of SMC has been reported in several studies. Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. Proliferation and accumulation of SMCs are believed to play important roles in the progression of macrophage-rich lesions to fibroatheromas. In a vicious cycle, atherosclerosis further impairs endothelial cell function (Figure 75-3). The animals used in this study are part of a larger study (Gerrity RA, Natarajan R, Nadler JL, Kimsey T, unpublished observations) in which the progression of diabetes-accelerated atherosclerosis has been followed for up to 48 weeks in the recently developed … 1. Because the mechanisms leading to the development of restenosis are likely different from those that produce primary atherosclerosis, a comparison of the pathophysiology of restenotic vs primary atherosclerotic plaque will enable us to better define the cellular events that lead to recurrent disease. ANEURSMAL DISEASE. Therefore, investigation of the role and behavior of SMCs is helpful to better understand the pathology of disease and its potential treatment. A number of factors affect SMC proliferation and migration, including hypertension, increased plasma cholesterol levels and oxidative stress. Static - Direct . 2 Vascular SMC … Introduction. Chronic endothelial injury 2. Smooth muscle cells are then activated and begin proliferation and migration. Further, high rates of SMC proliferation have been associated with atherosclerosis and hypertension . The presence of macrophage, as well as SMC proliferation, was observed in early lesions. The let-7 miRNA family plays a key role in modulating inflammatory responses. Vascular smooth muscle cell (SMC) proliferation and endothelial cell (EC) dysfunction are critical in the pathogenesis of atherosclerosis, including in the setting of diabetes. • The most recognized feature of atherosclerosis common to vein grafts and stents is macrophage infiltration, which best resembles ‘fatty streaks’. SMC apoptosis . The arterial smooth muscle cell (SMC), one of the three or four principal cell types in atherosclerosis, has been extensively studied over the years. Vascular remodeling because of smooth muscle cell (SMC) proliferation is a common process occurring in several vascular diseases, such as atherosclerosis, aortic aneurysm, post-transplant vasculopathy, restenosis after angioplasty, etc. Tnf-α is involved in activation of the large arteries with the PDGF (! 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