This proposal is for renewal of the A/S SCOR, a component interdisciplinary program of the Cardiovascular Research Institute of the University of California, San Francisco, located on the 13th floor of Moffitt/Long Hospital and the Medical Sciences Building. It is planned to continue and broaden the current program of research on lipoproteins and their relation to atherogenesis, utilizing methods of molecular and cell biology, immunology, macromolecular biochemistry, and mathematical biology. Emphasis throughout will be p)aced on the structure, synthesis, secretion, interaction with cells, and catabolism of plasma lipoproteins in experimental animals and model systems. The program also includes clinical investigations of lipoprotein and cholesterol metabolism in hyperlipoproteinemia and dyslipoproteinemia, the elucidation of new genetic lipoprotein disorders and research to develop more effective means to treat hyperlipoproteinemia, especially that of heterozygous familial hypercholesterolemia, and to determine the effect of this therapy upon lipid storage and atherosclerotic lesions. The total program includes a core lipid clinic, core laboratories and administrative support facilities, and eight individual projects: A-1: Role of liver in lipoprotein catabolism. A-2: Structure-function relationships of lecithin:cholesterol acyltransferase and cholesteryl ester transfer proteins. A-3: Regulation of cholesteryl ester transfer between lipoprotein species. A-4: Structure of lipoproteins. A-5: Subcellular origins of nascent plasma lipoproteins in liver. B-1: Characterization and pathogenesis of genetic hyperlipoproteinemias and dysbetalipoproteinemias and their relationship to atherosclerotic disease. B-2: Effect of normalization of plasma lipoprotein levels on lipoprotein and sterol metabolism and on atherosclerotic and xanthomatous lesions in heterozygous familial hypercholesterolemia. B-3: Plasma lipoprotein metabolism in non-insulin dependent diabetes, end-stage renal disease and familial hypercholesterolemia, and its relationship to documented atherosclerosis.
