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 ultracentrifugation and apo A-I containing lipoproteins (A-I Lp) were then isolated using anti-apo A-I immunoaffinity chromatography. The A-I Lp were further separated into two fractions with the use of anti-apo A-II immunoaffinity 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) or pravastatin (10 mg/day) reduced mean plasma total cholesterol concentrations by 24% (p < 0.01) and 16% (p < 0.05), respectively. Both drugs caused some reduction in lipoprotein lipase activity, but neither had any influence on the activity of hepatic triglyceride lipase or lecithin cholesterol acyltransferase. Their effects on HDL-cholesterol levels and apoprotein composition differed markedly. Probucol significantly decreased the HDL-cholesterol concentration, the plasma apo A-I/apo A-II ratio, and the number of large particles of diameter greater than 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 controls, and with the ratios before and after administration of probucol, a remarkable decrease in the level of Lp A-I was apparent. It is presumed that the decrease in HLD-cholesterol by prolonged probucol administration reflects the decrease of Lp A-I more than the decrease of Lp A-I/A-II.(ABSTRACT TRUNCATED AT 250 WORDS)
Kagami
A
A
Department of Internal Medicine, Aoto Hospital School of Medicine, Jikei University, Tokyo, Japan.
Ishikawa
T
T
Tada
N
N
Sakamoto
T
T
Mochizuki
K
K
Nagano
M
M
Moriguchi
E H
EH
Manabe
M
M
D016632:Apolipoprotein A-I / Q000032:analysis*; D016633:Apolipoprotein A-II / Q000032:analysis*; D008076:Cholesterol, HDL / Q000097:blood / Q000737:chemistry* / Q000187:drug effects; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008071:Lipoprotein Lipase / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D017035:Pravastatin / Q000627:therapeutic use*; D011341:Probucol / Q000627:therapeutic use*
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D008071:Lipoprotein Lipase; D017035:Pravastatin; D011341:Probucol