The physical exchange of phospholipids has been demonstrated between individual lipoprotein fraction in vivo and in vitro and between lipoproteins, platelets, erythrocyte membranes, and a variety of other cell types and tissues in vitro. The activities of plasma lipid transfer proteins which facilitate the transfer or exchange of cholesteryl esters, retinyl esters, triglycerides and phospholipids has been identified. However, attempts to isolate and characterize these proteins as well as their role in lipoprotein metabolism have not been established.
The specific aims of this proposal are (1) to isolate and characterize proteins from human plasma that facilitate the exchange or transfer of phospholipids among plasma liprproteins, (2) to establish a steady-state kinetic mechanism of exchange/transfer which will enable a determination of specificity for lipid class and lipoprotein or cell surface, (3) to prepare monoclonal antibodies to these proteins, and (4) to use the kinetic analyses and the monoclonal antibodies to selectively remove or inhibit these proteins to determine the function oif phospholipid transfer proteins in plasma and whole blood. From a combination of in vitro kinetic data on well-characterized model systems and the use of antibodies as specific reagents, it should be possible to establish the role of phospholipid transfer proteins in lipoprotein metabolism. Certain types of hyperlipoproteinemia are risk factors in atherosclerosis and premature cardiovascular disease. Our principal research interests have focused upon the identification of the molecular basis for these disorders. Studies on lipid transfer and exchange are an important part of an overall understanding of the structure and dynamics of plasma lipoproteins.
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