This Arteriosclerosis SCOR is concerned with the structure and function of lipoproteins, their synthesis and release from the cell and their interactions with artery wall cells in vitro and with arteries during atherogenesis and during therapy and regression of atherosclerosis. The program includes the investigation of serum lipoproteins from human and nonhuman primates in normal and hyperlipemic states using a combination of physical, enzymatic, chemical and immunochemical methods. Much of this effort is currently concentrated on the characterization of the major apoproteins. Studies of in vitro binding of apolipoproteins continue to be a major part of the work as are the physico-chemical properties of pure lipoprotein lipase from rat and monkey heart and adipose tissue and the purification and quantitative determinations of lecithin-cholesterol-acyl-transferase (LCAT). The lipoprotein biosynthesis studies using the orotic acid fatty liver model are being extended to work with the diabetic rat and to monkey liver. They include the isolation of hepatic polysomes involved in the synthesis of specific apoproteins as well as their respective mRNAs. The in vitro work with lipoproteins is concentrating on the mechanisms responsible for excessive SMC proliferation when hyperlipemic lipoproteins are added to the culture media as well as continuing study of how these cells accumulate and react to cholesterol from hyperlipemic serum. Particular emphasis is being placed on cholesterol ester synthesis and hydrolysis and the factors controlling cholesterol ester accumulation. A new component of this SCOR concerns a study of atherogenesis in nonhuman primates using two standardized forms of mechanical injury interacting with dietarily induced hyperlipemia. Quantitation of the reaction of various mesenchymal components of the artery wall at selected intervals following injury and during regression is a major goal of this project. The studies of advanced atherosclerosis in the arteries of primates is concentrating on cellular and chemical mechanisms of regression and on quantitation of the morphological and chemical aspects of this process in rhesus and cynomolgus monkeys.