Atherosclerosis atherosclerotic plaque

High levels of plasma cholesterol do not directly cause heart attacks. Rather, over long periods cholesterol is somehow involved in the progressive development of a disease of the arteries called atherosclerosis. Atherosclerotic plaques are complex lesions in arterial walls that contain abnormal deposits of cholesteryl esters. Precisely how high cholesterol levels in the plasma relate to the development of atherosclerosis is not understood and is a major frontier of medi-... 

Atherosclerosis is a chronic inflammation of the arterial vessel wall resulting in plaque formation that eventually may cause cardiovascular events, such as myocardial infarction or cerebral vascular accidents. The presence of autoimmune components in atherosclerosis is well established. Autoantibodies to heat-shock proteins and oxidized low-density lipoproteins (oxLDL) are prevalent in the circulation of patients with atherosclerosis, but the role of these autoantibodies is debated. While anti-oxLDL IgG antibodies may facilitate uptake of oxLDL by foam cells in the lesions, natural IgM antibodies directed to oxLDL may even protect from atherosclerosis. Atherosclerotic plaques also contain some T cells that are considered to be autoreactive, although the respective autoantigens have not yet been identified. These T cells are probably not involved in the plaque formation as such, but they may cause plaque instability, rupture, and subsequent clinical events. 

The expression of 15-LOX in atherosclerotic lesions is one of the major causes of LDL oxidative modification during atherosclerosis. To obtain the experimental evidence of a principal role of 15-LOX in atherosclerosis under in vivo conditions, Kuhn et al. [67] studied the structure of oxidized LDL isolated from the aorta of rabbits fed with a cholesterol-rich diet. It was found that specific LOX products were present in early atherosclerotic lesions. On the later stages of atherosclerosis the content of these products diminished while the amount of products originating from nonenzymatic lipid peroxidation increased. It was concluded that arachidonate 15-LOX is of pathophysiological importance at the early stages of atherosclerosis. Folcik et al. [68] demonstrated that 15-LOX contributed to the oxidation of LDL in human atherosclerotic plaques because they observed an increase in the stereospecificity of oxidation in oxidized products. Arachidonate 15-LOX is apparently more active in young human lesions and therefore, may be of pathophysiological importance for earlier atherosclerosis. In advanced human plaques nonenzymatic lipid peroxidation products prevailed [69],... 

The formation of atherosclerotic plaques is the underlying cause of coronary artery disease (CAD) and ACS in most patients. Endothelial dysfunction leads to the formation of fatty streaks in the coronary arteries and eventually to atherosclerotic plaques. Factors responsible for development of atherosclerosis include hypertension, age, male gender, tobacco use, diabetes mellitus, obesity, and dyslipidemia. 

Atherosclerosis, a disease of the vascular wall, is the substrate for the arterial forms of CVD. Atherosclerotic plaques exhibit a focal distribution along the arterial tree as a consequence of local conditions that favor their initiation and progression. Low or reversed shear stress, for example, contributes to plaque development, a process in which the regulation of several genes may be involved (Resnick and Gimbrone 1995). 

Fig. 9.5. Protection by SERMs against atherosclerosis has been researched in animals. In a model of ovariectomized rabbits, raloxifene reduced the cholesterol content in the inner part of the aorta more than placebo did (upper panel). This effect was more intense in animals treated with estradiol (Bjarnason et al. 1997). In contrast, in a different model of oophorectomized monkeys (lower panel), estradiol, and not raloxifene at two different dosages, significantly decreased the size of atherosclerotic plaques (Clarkson et al. 1998)...

Eompre Cultured cells are a useful model for pathology. If you want to see what is happening in atherosclerosis, for example, it is very difficult to work on the atherosclerotic plaque, because there are many cell types involved. In culture you can reproduce some of the events. For example, we have done balloon injury in the rat, and we lose RyRs when cells proliferate in situ. 

Atherosclerosis is a progressive vascular fibroproliferative-inflammatory disease. It is triggered, maintained, and driven by risk factors such as hypercholesterolemia, hyperlipidemia, and hypertonus [28]. The characteristic clinical manifestation of atherosclerosis is the atherosclerotic lesion, developing in the vessel wall (atherosclerotic plaque). 

Atherosclerosis The imaging of atherosclerosis with [ F]FDG PET was advanced and recent studies in rabbits showed that the tracer accumulated in macrophage-rich atherosclerotic plaques. It was assumed that the vascular macrophage activity can be quantified by p FlFDO PET [189]. Further studies in rabbits demonstrated that this imaging modality is useful for the clinical evaluation of therapeutic effects of drugs as well as for the development of new drugs that can reduce and inhibit inflammation of vulnerable plaques [190]. 

J.H.F. Rudd, K.S. Myers, S. Bansilal, J. Machac, A. Rafique, M. Farkouh, V. Fuster, Z.A. Fayad, Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible Implications for atherosclerosis therapy trials, J. Am. Coll. Cardiol. 50 (2007) 892-896. 

Hyperlipidemia can lead to atherosclerosis and subsequent cardiovascular incidents such as thrombosis and infarction. This condition is often treated by a combination of drug therapy and diet and life-style modifications. Pharmacologic interventions are typically targeted toward decreasing the synthesis of harmful (atherogenic) plasma components, including certain lipoproteins (IDL, LDL, VLDL) that are associated with atherosclerotic plaque formation. 

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