MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

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The role of antioxidant nutrients in lipid metabolism has not been well defined. We have found that rats fed a diet deficient in antioxidant nutrients (selenium and vitamin E) develop elevated levels of low density lipoprotein-cholesterol (LDL-cho). The development of elevated LDL-cho in spontaneously hypertensive (SHR) rats fed a 1% cholesterol diet deficient in selenium (Se) and vitamin E is particularly accelerated compared with other rat strains. Our primary research objective is to characterize and determine the metabolic and biochemical mechanism(s) responsible for the alterations in rat plasma lipoprotein levels resulting from dietary deficiencies of antioxidant nutrients. Cholesterol free diets, as well as diets containing 1% cholesterol will be utilized. The animals to be studied are inbred SHR rats, and control normotensive (WKY) rats. We will study lipoprotein composition, LDL catabolism, and VLDL synthesis in antioxidant deficient and sufficient rats. The plasma clearance and tissue uptake of LDL will be determined in intact animals. LDL uptake and VLDL synthesis will be studied in a liver perfusion system. A second long term goal is to determine if lipid peroxidation is a molecular mechanism important in causing the observed alterations in lipoprotein-cholesterol levels. Human and animal LDL will be subjected to a variety of in vitro peroxidation systems and the plasma clearance and uptake of the peroxidized LDL compared to that of LDL chemically modified by well characterized procedures such as reductive methylation of lysine residues. This work may have health related significance because the damaging process of lipid peroxidation appears to be an important factor in the etiology of human atherosclerosis and cardiomyopathy.