The overall goal of the proposed project is to investigate the role which phospholipids and apoproteins play in the hepatic recognition and uptake of remnants of triacylglycerol (TG)-rich lipoproteins. Remnants of TG-rich lipoproteins are formed in the vascular space as a result of the action of lipoprotein lipase. Compared to the intact lipoproteins (chylomicrons and very low density lipoproteins) remnants are enriched in cholesterol and apoproteins E and B and depleted in TG, phospholipids and apoproteins C and A. As opposed to the intact lipoproteins, remnants are efficiently removed from circulation by a process which involves the recognition and binding of apoprotein E by specific receptors on the surface of liver cells. The mechanism whereby cell receptors bind the remnant apoproteins, but not the apoproteins of intact lipoproteins has not been elucidated. Based on indirect evidence apoprotein C and phospholipids have been suggested to play a role in this process. We propose to selectively alter the apoprotein and phospholipid composition of intact rat lymph chylomicrons and chylomicron remnants to determine what changes are necessary for their recognition by the hepatic receptors in the intact organ and in isolated plasma membranes. Elucidation of the mechanism whereby remnants are removed from circulation by the liver may be of importance in the development of strategies for the prevention and management of atherosclerosis.
