Dietary polyunsaturated fat is believed to be beneficial for decreasing the risk of premature heart disease because it lowers plasma cholesterol concentrations. However, with this dietary fat high density lipoprotein (HDL) cholesterol concentration also decreases and low HDL cholesterol concentration is a risk factor for heart disease. We have shown that polyunsaturated fat fed monkeys had less atherosclerosis than saturated fat fed monkeys in spite of lower HDL concentration. The studies of this proposal are designed to determine if the total serum cholesterol lowering induced by a diet rich in monounsaturated fat is as beneficial in decreasing atherosclerosis in monkeys as that induced by a diet rich in polyunsaturated fat, since the former has been shown to lower low density lipoprotein (LDL) concentration without lowering that of HDL. In order to begin to understand the mechanisms of dietary fat modifications of plasma HDL concentration, the production of HDL particles by the isolated, perfused livers of monkeys will be studied. In monkeys, hepatic HDL particles are produced as precursor lipoproteins deficient in cholesterol esters. Using livers isolated from animals fed each type of dietary fat, we will measure the kinds of precursor particles produced as characterized by their apoprotein and lipid composition and their size. The amounts of the various precursor particles produced during liver perfusion will be measured as will the amounts of the individual HDL apoproteins. The conversion of each of the precursor lipoproteins into mature plasma HDL will be examined to determine their relationship to the plasma HDL subclasses. Detailed analyses of atherosclerosis will be made in each of the animals in which the plasma HDL and liver perfusate HDL have been analyzed. These studies will provide an opportunity to learn specific aspects of HDL metabolism important in atherosclerosis development in primates.
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