PLATELET-MEDIATED CHOLESTEROL ACCUMULATION WITHIN VASCULAR-ASSOCIATED CELLS

点击翻译按钮获取中文摘要

The purpose of this project is to examine mechaniams of cellular cholesteryl ester accumulation that may be mediated by platelets. Washed rate platelets have been incubated with smooth muscle cells, macrophages, fibroblasts, and endothelian cells. In addition, platelet-free supernatants, prepared from unactivated or activated incubated platelets have been added to cultures of these cells. As reported last year, activated rat platelets induce cholesteryl ester accumulation in cultured rate aortic smooth muscle cells. We have determined this year that platelet activation by collagen is equally effective as is platelet activation with thrombin. Histochemical detection of smooth muscle cholesteryl ester accumulation has been confirmed chemically as platelet-mediated stimulation of cholesteryl ester synthewsis. Interestingly, cholesteryl ester accumulates in a subpopulation of cultured human aortic smooth muscle cells, suggesting that smooth muscle cells may be comprised of at least two functional subtypes with respect to platelet-mediated cholesterol accumulation. We have also determined that platelets release substantial amounts of unesterified cholesterol when they are activated. Cholesterol release is calcium dependent and can be totally or partially blocked by a variety of anti-platet drugs. The possible role of platelets in promoting smooth muscle cell proliferation within atherosclerotic lesions has been previously recognized. Our research has shown that platelet can mediate cholesteryl ester accumulation within cultured vascular-derived smooth muscle cells. The possible role of platelets in mediating cholesterol accumulation within atherosclerotic lesions must now also be considered in evaluating the pathogenesis of atherosclerosis.