Effect of hydroxymethylglutaryl-CoA reductase inhibitors on the functional properties of erythrocyte membranes.
We studied 56 patients affected by primary hypercholesterolemia treated with placebo for 1 month and with simvastatin (20 mg/day) or pravastatin (20 mg/day) for 6 months during a double-blind clinical trial. At 1-month intervals we determined the following parameters in the serum: total and HDL cholesterol, triglycerides, and apolipoprotein A-1 and B. At the same time intervals we also determined the cholesterol and phospholipid concentration, the Na+/K+ ATPase activity, and the fluidity of erythrocyte membranes. Our results demonstrated the following modifications in the erythrocyte membranes during simvastatin and pravastatin treatments: (1) an initial increase in cholesterol concentration and in cholesterol/phospholipid molar ratio, with a significant decrease only after 4 months; (2) a similar behavior of membrane fluidity, with an initial decrease and an elevation after 4 months; (3) an increase in the Na+/K+ ATPase activity only after 4 months. We hypothesize that simvastatin and pravastatin not only inhibit the hepatic synthesis of cholesterol, but also modify the cholesterol exchange between plasma and the erythrocyte membrane.
Rabini
R A
RA
Istituto di Biochimica, Facoltà di Medicina, Università di Ancona, Italy.
Polenta
M
M
Staffolani
R
R
Tocchini
M
M
Signore
R
R
Testa
I
I
Mazzanti
L
L
D000293:Adolescent; D000328:Adult; D002784:Cholesterol / Q000097:blood; D004910:Erythrocyte Membrane / Q000187:drug effects*; D005260:Female; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008148:Lovastatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000097:blood; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use; D019821:Simvastatin; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008563:Membrane Lipids; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D000254:Sodium-Potassium-Exchanging ATPase; D017035:Pravastatin