This research program will use the baboon (Papio sp.) to study the roles of diet, genetics, and environmental stress in the etiology and pathogenesis of atherosclerosis. Project 1 examines interactions between dietary cholesterol and type of fat in pedigreed baboons with genetic dyslipoproteinemias. It will focus on baboons that produce, while consuming a saturated fat diet, lipoproteins (designated F 9-28) of density intermediate between that of LDL and that of HDL, and rich in apoproteins A-I and E. It also examines the possible metabolic basis of this dyslipoproteinemia through studies of chylomicron catabolism and of lipoprotein metabolism in perfused livers. Project 2 completes a long term experiment in which pedigreed baboons are being reared from birth to adulthood on different cholesterol and fat enriched diets to determine both immediate and deferred effects on cholesterol absorption and turnover, serum lipoproteins, and atherosclerosis. Project 3 determines genetic markers in a large number of pedigreed baboons to identify major genes involved in the control of serum lipoprotein concentrations and in atherogenesis. The markers include the F 9-28 lipoproteins, apolipoprotein concentrations, and isoforms of apo E, serum esterase, acid lipase, and the third component of complement. Project 4 applies quantitative and statistical genetic techniques, including segregation and linkage analyses, to data generated in other projects to identify major gene effects on lipoproteins and atherosclerosis; and uses selective matings to confirm suspected major genes. Projects 5 and 6 induce two contrasting forms of experimental stress (dominance hierarchy perturbation and shock avoidance) in baboons fed an atherogenic diet to determine their effects on serum concentrations of lipoproteins, cortisol, and testosterone, and on atherosclerosis. These projects are supported by Lipid Biochemistry, Pathology, Biometry, Veterinary Services, and Administrative core units.
Showing the most recent 10 out of 291 publications
