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 hyothesize that simvastatin and pravastatin not only inhibit the hepatic synthesis of cholesterol, but also modify the cholesterol exchange between plasma and the erythrocyte membrane.