Current in vitro models of atherosclerosis. The animals used in this study are part of a larger study (Gerrity RA, Natarajan R, Nadler JL, Kimsey T, unpublished observations) in which the progression of diabetes-accelerated atherosclerosis has been followed for up to 48 weeks in the recently developed … atherosclerosis are not well understood. Chronic endothelial injury 2. Models of atherosclerosis consist of combinations of: Endothelial Cells (EC), Smooth Muscle Cells (SMC) and … The low-density lipoprotein … The presence of macrophage, as well as SMC proliferation, was observed in early lesions. The increase in SMC proliferation is considered an important step in the pathogenesis of atherosclerosis (54, 55). 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. 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. Overexpression of Smad3 enhanced whereas inhibition of Smad3 decreased cell proliferation. Factors releasedÆSMC recruitment 6. Atherosclerosis involves multiple processes including endothelial dysfunction, inflammation, vascular proliferation and matrix alteration. The let-7 miRNA family plays a key role in modulating inflammatory responses. Hypothetical sequence of cellular interactions in atherosclerosis. Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. ANEURSMAL DISEASE. The low-density lipoprotein receptor–related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). Thus, their dysfunction plays a key role in atherosclerosis. 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. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at … 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 … 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). Vascular smooth muscle cell (SMC) proliferation and endothelial cell (EC) dysfunction are critical in the pathogenesis of atherosclerosis, including in the setting of diabetes. DISCUSSION Diabetes markedly accelerates SMC proliferation and accumulation in atherosclerotic lesions. Monocyte adhesion to endothelium 4 Platelet adhesion basic tenets 4. The low-density lipoprotein receptor-related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). Monocytes inhibit SMC proliferation [93] Human ASMC, Monocytes . Summary. Introduction. Here we show that LRP1 forms a complex with the PDGF receptor (PDGFR). Atherosclerosis is a chronic, progressive lipid driven inflammatory disease. SMC proliferation . Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. 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. Koyama and colleagues found that plating SMCs on top of polymerized two dimensional (2-D) type I collagen maintained SMC quiescence Static - Direct or Indirect - Transwell The majority of cardiovascular diseases are the result of vascular remodeling underlying the development of atherosclerosis and its occlusive complications. Therefore, investigation of the role and behavior of SMCs is helpful to better understand the pathology of disease and its potential treatment. 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 . 2 Vascular SMC … 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. Static - Direct . Proliferation and accumulation of SMCs are believed to play important roles in the progression of macrophage-rich lesions to fibroatheromas. Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. Smooth muscle cell (SMC) proliferation in the arterial wall has been implicated as having a central role in hypertension, atherosclerosis, and restenosis after angioplasty. Atherosclerosis is a lipid‐driven inflammatory disease characterised by plaque formation in the large arteries. 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. 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. Atherosclerosis is a chronic inflammatory response of the artil llt dthlilijterial wall to endothelial injury. ... Because the mechanisms leading to the development of restenosis are likely different from those that produce primary atherosclerosis, a comparison of the pathophysiology of A number of factors affect SMC proliferation and migration, including hypertension, increased plasma cholesterol levels and oxidative stress. 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). 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 Further, high rates of SMC proliferation have been associated with atherosclerosis and hypertension . 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. • SMC proliferation without macrophage foam cell infiltration is frequently observed in BMS implants, especially in those aged <5 years. Magnier-Gaubil et al. Involves the tunica intima of the arterial wall. 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. Considerable in vivo studies support the role of free radical reactions in atherogenesis and atherosclerotic‐related coronary heart disease. (J Vasc Surg 2009;49:1289-95.) 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 . In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. 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 Smooth muscle cells are then activated and begin proliferation and migration. Accumulation of lipoproteins (LDL mainly) 3. • The most recognized feature of atherosclerosis common to vein grafts and stents is macrophage infiltration, which best resembles ‘fatty streaks’. showed that TGF-β inhibits PDGF-stimulated proliferation of SMC. Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of 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. In westernized societies, it is the underlying cause of about 50% of all deaths. Atherosclerosis is an autoimmune disease caused by self- and non-self-antigens contributing to excessive activation of T and B cell immune responses. SMC proliferation and the pathophysiology of restenosis in humans. Platelet adhesion 5. In a vicious cycle, atherosclerosis further impairs endothelial cell function (Figure 75-3). Furthermore, TNF-α is involved in activation of the mitogen-activated protein kinase cascade, leading to vascular SMC migration and proliferation (31,32,34). 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. Here we report that let-7 levels are decreased in diabetic human carotid plaques and in a model of diabetes-associated 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 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. 1. 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). The molecular mechanism underlying SMC proliferation, however, is not completely understood. ... (due to TGF and PDGF released by platelets and thrombin itself causes SMC proliferation and ECM deposition) contributes to leison evolution and plaque growth. 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. Are important events in the pathogenesis of atherosclerosis common to vein grafts and stents is infiltration. 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