PATHOBIOLOGICAL DETERMINANTS OF ATHEROSCLEROSIS IN YOUTH

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The overall goal is to determine, by digitial fluorescence, the 3-dimensional distribution of lipid inclusions, macrophages and smooth muscle cells in the in anatomically defined segments of human left anterior descending coronary artery. Changes in the number, the relative proportions and the spatial distribution of these vessel wall components as a function of the age-dependent degenerative changes of atherosclerosis are not adequately documented. The objectivity of image analysis is needed to deduce the distribution of lipid inclusions and specific cells in situ. A computer analysis of the ratio of specific fluorescence intensity values, acquired without loss of signal by photobleaching, will allow comparisons on a pixel by pixel basis and for successive image planes. The relationships between cells and extracellular components and their involvement in the apparent progression of fatty streaks to fibroatheromatous plaques can be analyzed by computer based methods not previously available. These studies will attempt to answer the specific questions. (1) Do the arterial intimal lesions that are characteristic of later childhood (fatty streaks) progress into the lesions that, in adulthood, are closely associated with arterial occlusion and ischemic disease (fibrous plaques)? At what age and under what conditions to "transitional" lesions (that is, lesions that have characteristics of both fatty streaks and fibrous plaques) occur? (2) If the progression hypothesized in (1) does take place, what are the earliest detectable changes in the fatty streak that indicate this progression? More specifically, are there differeces in the lipid or lipoprotein composition and location, endothelial covering, fibrin and platelet localization, monocyte/macrophage/foam cell population, smooth muscle cell number or structure, trace element and electrolyte composition, or connective tissue composition of the fatty streaks which are most likely to progress to fibrous plaques, as compared to fatty streaks which are not likely to progress?