This study seeks to clarify the initiation and development of the lipid-rich core of the atherosclerotic fibrous plaque, as discerned in human aorta and coronary arteries from autopsy cases. Quantitative morphologic, ultrastructural, and biochemical studies will focus on perifibrous lipid deposition, the smallest detectable core regions of fibrous plaques, transitional forms of fatty streaks, and the border region surrounding the lipid-rich core inlarger fibrous plaques. A new technique of boundary analysis will test the hypothesis that small lipid droplets, the ultrastructural counterpart of perifibrous lipid, are associated spatially with basment membrane-like material in the intima. The smallest (3-dimensionally) detectable regions of necrosis and cholesterol crystal formation in fibrous plaques will be examined to determine, primarily, the setting in which they occur, i. e. , depth within the intima and presence of cellular or extracellular droplet lipid, biochemical lipid patterns, and ultrastructural alterations in surrounding tissue. In studying large fibrous plaques, primary goals are to determine various cellular and extracellular volume fractions within specifically defined transition zones bordering the lipid-rich core, the dependence of these distributions on the presence of capillaries or inflammatory cells, and free-esterified cholesterol ratios as a function of location. The importance of the necrotic, lipid-rich core of the fibrous plaque is emphasized by its tendency of undemine the nonthrombotic luminal surface, eventuating in ulceration or rupture of the plaque and accute thrombotic or thromboembolic events. Quantitative pathologic data obtained in this studywill substnatially test hypotheses related to the origin of the core region and will aid in the formulation of hypotheses on its spread and growth
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