Knowledge of human apolipoprotein structure has contributed to the understanding of normal and abnormal lipid transport and metabolism. Recent studies have shown that apolipoprotein (apo) A-1 and B are closely associated with the presence of atherosclerosis. It is known that a structural defect of apo A-1 due to amino acid substitutions will eventually lead to the development of coronary artery disease (CAD). However, it is not clear at the present time whether structural defects in apo-B can give rise to clinically significant disease. This proposal is designed to utilize a number of immunochemical tools to probe the orientation and structure of apolipoproteins and of lipoprotein particles. The definition of the antigenic sites of apolipoproteins will permit the use of blocking antibodies to map the physiologically active sites on the apolipoprotein molecule. It will also permit the probing of possible structural differences in patients with CAD. Short term goals of the present studies will be to: a) map out the antigenic structure of apo A-I; b) determine the differences in the immunochemical properties of apo B between the patients with and without CAD. Long term goals will be to: a) establish the apolipoprotein and lipid relationship in patients with coronary artery disease; b) sort out the various apo B components with monoclonal antibodies and to delineate their possible atherogenic role; c) provide the antigenic structure and immunochemical properties of apolipoproteins and lipoproteins; and d) utilize monoclonal antibodies as probes to study the structure and function of lipoproteins.
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