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
✍ Scribed by Akihiko Kagami; Toshitsugu Ishikawa; Norio Tada; Takuya Sakamoto; Keiko Mochizuki; Makoto Nagano; Emilio Hideyuki Moriguchi; Mitsuhisa Manabe
- Publisher
- Elsevier Science
- Year
- 1993
- Tongue
- English
- Weight
- 705 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0009-9120
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✦ Synopsis
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 HDLcholesterol 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 probucoltreated 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 HDL-cholesterol by prolonged probucol administration 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 change HDL-cholesterol levels, the plasma apo A-I/apo A-II ratio, or HDL particle size.