Causal relationship between removal efficiency of low density lipoproteins and their composition following cholesterol feeding and cholestyramine therapy

Abstract

The origin of cholesterol-rich low density lipoprotein (LDL) in diet-induced hypercholesterolemia was investigated by simultaneous examination of LDL composition and 125I-LDL plasma clearance in control and in cholesterol-fed rabbits treated or not with cholestyramine. The results show a straight relationship between LDL plasma clearance and the cholesterol ester/triglyceride ratio among the three experimental groups. Cholesterol-fed rabbits present a marked increase in the cholesterol ester/triglyceride ratio of LDL associated with an impairment in the catabolism of LDL, isolated from normal rabbits, as indicated by their fractional catabolic rate (FCR). Both parameters, cholesterol ester content and FCR of the LDL remain intermediate in cholesterol-fed rabbits treated with cholestyramine. The intravascular transformation of labeled LDL from normal rabbits was evaluated by the study of changes in their density profile. The increase in modal density of LDL after 7 hours of exposure in the blood stream is accentuated in cholesterol fed-rabbits. Therefore the intravascular transformation of LDL depends on the removal efficiency of the recipient animals. Taken together the findings support the hypothesis that abnormal LDL mainly results from supplementary intravascular degradation as a consequence of increased lifetime. Additional data concerning the composition of the very low density lipoproteins (VLDL) and intermediate density lipoproteins (LDL) are given. Cholestyramine has clear preventive effects on the alteration of these lipoproteins following cholesterol feeding suggesting that the mechanism proposed for LDL alteration is involved in the appearance of the other apo-B- containing lipoproteins.