NONHUMAN PRIMATE: DEVELOPMENT OF LIPOPROTEIN SUBCLASSES

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This is a pilot project to investigate the development of lipoprotein subclasses in cynomolgus monkeys at the NHLBI- supported primate center at Bowman Gray School of Medicine. The long-range objectives of the study are to understand how adult subclass heterogeneity has evolved, whether subclass patterns are heritable traits detectable in early life, and whether subclass patterns in the young serve as markers for the early detection of increased risk to cardiovascular disease. Specific questions to be addressed in this study are designed to obtain preliminary data on HDL and LDL subclass distribution as a function of development and include: (1) how does lipoprotein subclass distribution in the neonate differ from that of the adult; (2) how soon after birth does the subclass profile assume adult characteristics; (3) what is the relationship between apolipoprotein and lipid levels and specific HDL and LDL subclasses; and (4) can one detect HDL and LDL subclasses which are related to the hyper- and hypocholesterolemic response in animals challenged with dietary cholesterol? HDL and LDL subclass heterogeneity will be evaluated on progeny from specific matings between monkeys which are hypocholesterolemic responders to dietary cholesterol and those which are hypercholesterolemic responders to dietary cholesterol. Subclass distribution will be evaluated by non-denaturing gradient gel electrophoresis at several time points during early development, including: birth; 3, 7, 14, and 28 days postpartum; and 3, 6, and 12 months. Patterns will be correlated with lipid and apolipoprotein levels and with apolipoprotein AI, B, and E distribution as determined by Western blotting. The study should provide preliminary data on whether it is possible to identify, early in life, lipoprotein subclasses which might be deemed risk factors in the development of cardiovascular disease.