The overall theme of this application is the role of abnormal triglyceride and fatty acid metabolism in the etiology of atherosclerosis. Project 0006 (W. and J. Patsch) is on postprandial lipoproteins and has as its major goal identification of the molecular basis for the observed correlation between the duration of postprandial lipemia and the incidence of coronary artery disease. Project 0010 (J.B. Massey) investigates the role of lipid transfer and lipid transfer proteins on lipoprotein metabolism in vitro and in vivo. Project 0011 (H.J. Pownall) focuses on the mechanism and role of a plasma peptide that stimulates the formation of intracellular fatty acid esters. Both Projects 0010-0011 use the hamster as an animal model for diet-induced atherosclerosis. In Project 0012 (J.D. Morrisett), synthesis and catabolism of Lp[a] will be studied, with special emphasis given to the effects of postprandial lipemia on the formation of triglyceride-rich Lp[a] particles and their lipolysis in vivo. Project 0013: D.P. Via) is designed to determine how specific lipoproteins and their components regulate cell-specific cytokine production and secretion. The goal of Project 0014 (L.C. Smith) is to determine the mechanism by which plasma triglycerides are hydrolyzed and to use recombinant DNA methods to identify the functional regions of the plasma lipases and apoC-II. Project 0009 (L. Chan) uses transgenic animals as an in vivo vector for the identification of functional regions in apolipoprotein B-100 in VLDL and LDL. All projects are designed to identify the special role that abnormal triglyceride metabolism has in atherogenesis. In addition to an (A) Administrative Core, these projects are supported by the following research cores: (9005) Cell and Molecular Biology, (9004) Peptide Sequencing and Amino Acid Analysis, and (9002) Lipoprotein Isolation and Analysis.
