Structural and functional changes of rhesus serum low density lipoproteins during cycles of diet-induced hypercholesterolemia.

Over the course of a 2-year study, two male rhesus monkeys underwent episodes of diet-induced hypercholesterolemia (from a diet supplemented with 25% coconut oil and 2% cholesterol) followed by regression phases in which the animals received a low fat Purina chow diet. During the induction of hypercholesterolemia, serum cholesterol, apo B, saturation of low density lipoprotein (LDL) cholesteryl ester fatty acyl chains, and the ability of the serum to stimulate cholesterol esterification by smooth muscle cells rose immediately and in parallel, whereas there was a lag period before the serum became mitogenic to smooth muscle cells. Concurrently, there were important changes in the density, size, chemistry, and concentration of the LDL species in the rhesus serum; induced LDL shifted from the LDL-II to the LDL-I density region with increasing cholesterol concentration. Both structural and functional changes were reversed upon return to a normal Purina chow diet, although at different rates. Serum cholesterol, apo B, and the rate of cholesterol esterification in smooth muscle cells promoted by the serum declined in parallel while the mitogenicity of the serum to smooth muscle cells and the degree of saturation of LDL cholesteryl ester fatty acids took longer to return to normal values. In fact, there was an immediate and dramatic rise in saturation upon reversal before the LDL cholesteryl ester fatty acyl chains returned to their normal composition. The Lp(a) particles did not increase in either concentration or size in response to the test diet, although the change in their lipid composition was similar to those of the other LDL species. The studies indicate that dietary manipulations affect the physicochemical properties of the LDL particles, and that the resultant structural alterations are accompanied by changed in vitro cellular response, suggestive of a greater atherogenicity.