ROLE OF THE ARTERIAL WALL IN ATHEROSCLEROSIS

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The major objectives of the project are to elucidate (1) the interactions of hypertension and lipoproteins in the pathogenesis of atherosclerosis; (2) the role of the smooth muscle cell and endothelial cell in vascular permeability and the biosynthesis of connective tissue proteins; (3) role of acid mucopolysaccharides and proteoglycans in atherosclerosis and their relationship to lipid, lipoprotein and calcium deposition in the plaque; (4) the role of platelets and the platelet "release action" in atherosclerosis; (5) role of physico-chemical changes of lipid and lipoproteins in atherosclerosis; (6) role of lipoprotein interactions with acid mucopolysaccharides, connective tissue proteins and calcium in atherosclerosis. The proposed programs will be carried out in subhuman primates (cynomolgus monkey) with experimental atherosclerosis and/or hypertension and in smooth muscle cells and endothelial cells grown in cell culture. These studies will focus on the correlations to the biochemical, metabolic and morphologic changes in the artery during the development and treatment of atherosclerotic and/or hypertensive vascular disease.