EFFECTS OF PROBUCOL AND PRAVASTATIN ON PLASMA-LIPIDS, ACTIVITIES OF POSTHEPARIN LIPOPROTEIN-LIPASE, AND LECITHIN-CHOLESTEROL ACYLTRANSFERASE AND APO A-I CONTAINING LIPOPROTEINS WITH AND WITHOUT APO A-II IN PATIENTS WITH MODERATE HYPERCHOLESTEROLEMIA

In this study, plasma HDL fractions were separated by ultracentrifugat ion and apo A-I containing lipoproteins (A-I Lp) were then isolated us ing anti-apo A-I immunoaffinity chromatography. The A-I Lp were furthe r separated into two fractions with the use of anti-apo A-II immunoaff inity chromatography. One fraction, Lp A-I, contained apo A-I without apo A-II, while the other, Lp A-I/A-II, contained both apo A-I and apo A-II. These techniques were applied to investigate the changes in HDL apoprotein composition in hypercholesterolemic subjects treated with either probucol or pravastatin. Treatment with probucol (500 mg/day) o r pravastatin (10 mg/day) reduced mean plasma total cholesterol concen trations by 24% (p < 0.01) and 16% (p < 0.05), respectively. Both drug s caused some reduction in lipoprotein lipase activity, but neither ha d any influence on the activity of hepatic triglyceride lipase or leci thin cholesterol acyltransferase. Their effects on HDL-cholesterol lev els and apoprotein composition differed markedly. Probucol significant ly decreased the HDL-cholesterol concentration, the plasma apo A-I/apo A-II ratio, and the number of large particles of diameter greater tha n 10.4 nm. When the ratios of Lp A-I and Lp A-I/A-II for the probucol- treated subjects were compared with those in the normolipidemic contro ls, and with the ratios before and after administration of probucol, a remarkable decrease in the level of Lp A-I was apparent. It is presum ed that the decrease in HDL-cholesterol by prolonged probucol administ ration reflects the decrease of Lp A-I more than the decrease of Lp A- I/A-II. In contrast to probucol, pravastatin did not significantly cha nge HDL-cholesterol levels, the plasma apo A-I/apo A-II ratio, or HDL particle size.