Brief overview of the mounting evidence that atherosclerosis is both preventable and reversible.
The major life-threatening events in advanced atherosclerosis are precipitated by the plaque. Thrombosis in the muscular arteries and rupture of the large elastic arteries usually follows rupture of the plaque's fibrous cap. The smooth muscle cell (SMC) participates in many aspects of the atherosclerotic process: lipid uptake, synthesis of plaque components, and cell proliferation. The latter is a particularly significant aspect of the disease. High serum cholesterol levels stimulate proliferation of arterial medial cells; low-density lipoproteins (LDL) from hyperlipidemic plaques induce ingress and storage of cholesterol ester. These effects are inhibited by high-density lipoproteins (HDL). Endothelial injury may be an important part of the pathogenesis of some atherosclerotic plaques because powerful growth factors actively stimulate SMC proliferation, even when other risk factors are absent. Utilization of animal models of atherosclerosis, especially nonhuman primate models, has led to great progress in understanding this disease process. In controlled feeding experiments, severe atherosclerosis has been produced in rhesus monkeys by means of a high fat, high cholesterol diet. Animals then placed on a low fat, low cholesterol diet, or given cholestyramine, or a combination of these two approaches, showed a remarkable decrease in the size of their atherosclerotic plaques. Many epidemiologic studies, as well as more recent prospective intervention studies involving bile acid sequestrants, indicate by imaging techniques that plaque regression takes place in humans.
Wissler
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Multicenter Cooperative Study of the Pathobiological Determinants of Atherosclerosis in Youth, University of Chicago Medical Center, Illinois 60637.
Vesselinovitch
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D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D008076:Cholesterol, HDL / Q000097:blood; D006801:Humans; D008955:Models, Cardiovascular
D008076:Cholesterol, HDL