Hypocholesterolemic effect of pravastatin is associated with increased content of antioxidant vitamin-E in cholesterol fractions.
Metabolic studies support the findings that antioxidants inhibit atherosclerosis. Treatment with vitamin E reduced both the susceptibility of low density lipoprotein cholesterol (LDL-C) to in vivo lipid peroxidation and atherosclerosis and smooth muscle proliferation. Thus the aim of present study was to examine metabolic consequences of reduced plasma LDL-C during hypolipidemic therapy and the distribution of antioxidant vitamin E. A group of 10 patients (4 men, 6 women, age 35-65y) with familial hypercholesterolaemia was treated using pravastatin (Lipostat Bristol Myers Squibb, 40 mg daily at 6:00 PM). Blood samples were examined before treatment, after 4 and 8 weeks of therapy. After ultracentrifugation, samples were analyzed for lipoprotein fractions and the content of vitamin E and cholesterol. Pravastatin reduced both total cholesterol (9.85 +/- 0.74 vs. 6.81 +/- 0.51 mmol/1; p < 0.01), LDL-C (6.42 +/- 0.45 vs. 4.51 +/- 0.45 mmol/l; p < 0.01), light LDL1-C (4.56 +/- 0.50 vs. 3.11 +/- 0.34 mmol/l; p < 0.05) and dense LDL2-C (1.86 +/- 0.27 vs. 1.42 +/- 0.17 mmol/l; ns). Serum vitamin E was reduced during hypolipidemic therapy in the fraction of total, LDL1, LDL2, and VLDL-cholesterol. However, the ratio of serum vitamin E/total serum cholesterol (4.57 +/- 0.32 vs. 5.12 +/- 0.37 mmol/l/mmol/l; p < 0.05) and ratio of LDL2-C vitamin E/LDL2-C (3.92 +/- 0.07 vs. 4.64 +/- 0.37 mmol/l/mmol/l; p = 0.08) increased in comparison to pre-treatment values. We conclude that pravastatin therapy may possess anti-atherogenic properties which involve not only its hypocholesterolemic effect, but also its favorable effects on the distribution of LDL subclasses and the content of antioxidant vitamin E in atherogenic lipoproteins.
Bláha
V
V
Department of Metabolic Care and Gerontology, Charles University, Faculty of Medicine and Teaching Hospital, Hradec Králové.
Zadák
Z
Z
Solichová
D
D
Brátová
M
M
Havel
E
E
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood / Q000737:chemistry*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D014810:Vitamin E / Q000032:analysis* / Q000097:blood
D000924:Anticholesteremic Agents; D000975:Antioxidants; D008078:Cholesterol, LDL; D014810:Vitamin E; D002784:Cholesterol; D017035:Pravastatin