The objective of this SCOR program is to elucidate, in seven projects, the relationship between plasma lipoproteins and atherosclerosis by a broad range of investigations of the structure and function of the plasma lipoproteins under normal conditions and in states associated with accelerated atherogenesis. 1) Structure and function of apolipoproteins: This Project will investigate the physical structure and functional domains of apolipoprotein B, determine the structure of several newly recognized apolipoproteins, and the structure of lipoproteins eluted from atherosclerotic plaques. 2) Structure-function relationships of catalytic proteins in the reverse cholesterol transport pathway: This Project will utilize site-directed mutagenesis to elucidate functionally important regions in these key proteins of reverse cholesterol transport, by which cholesterol is removed from atherosclerotic plaques. 3) Assembly of nascent plasma lipoproteins by hepatocytes: This Project will elucidate the steps in the assembly of potentially atherogenic and antiatherogenic lipoproteins in the liver. 4) Role of the liver in lipoprotein catabolism: This Project will elucidate mechanisms by which atherogenic lipoproteins are removed from the blood and the regulation of these processes. Projects 3 and 4 may lead to new approaches to regulate the concentration of atherogenic and antiatherogenic lipoproteins in the blood. 5) Reverse cholesterol transport and the arterial wall: This Project will determine how species of high density lipoproteins take up and esterify cell and plasma cholesterol and deliver it to other lipoproteins for removal by the liver, and will advance our understanding of the mechanisms by which cholesterol is removed from arterial walls. 6) Genetic dyslipoproteinemia: genomic determinants and functional consequences: This project, by elucidating genomic mechanisms of familial dyslipoproteinemias and the effects of these disorders upon lipoprotein interconversions and catabolism, will increase our understanding of the basis of atherogenic dyslipoproteinemias. 7) Postprandial lipid metabolism in coronary artery disease: This project will investigate abnormalities of plasma triglyceride and cholesterol transport in the postprandial state to provide new insights into the dynamic changes in metabolism of atherogenic and antiatherogenic lipoproteins after fat ingestion. The SCOR will be supported by three Core Units: a Lipid Clinic, Laboratories, and an Administrative Unit. The entire program will form a cohesive and coherent attack upon central issues of the relationship between plasma lipoproteins and atherogenesis.
