Influence of cholesterol lowering on plasma membrane lipids and cationic transport system

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Abstract

Background

In order to determine whether alterations in membrane lipids affect transmembrane cationic transport systems in erythrocytes and platelets, cationic fluxes and intracellular cationic concentrations were measured in hypercholesterolaemic patients before and during administration of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Methods

After a 1-month run-in placebo period on a lipid-lowering diet the patients were treated, in a double-blind manner, with either placebo (n=25) or pravastatin (n=25) for 6 months. Placebo or pravastatin (10 mg during the first month, 20 mg during the second month and 40 mg during the remaining 4 months) was administered once a day in the evening.

Results

Compared with the placebo group, the erythrocyte and platelet membrane cholesterol content was reduced in the patients treated with pravastatin. The intra-erythrocyte and intraplatelet Na+ concentration was reduced during pravastatin administration, whereas the activity of the erythrocyte and platelet Na+-K+ pump was increased. However, the intra-erythrocyte and intraplatelet K+, Mg2+ and cytosolic Ca2+ concentrations, and water content, as well as the activities of the erythrocyte Na+-Li+ countertransporter and Na+, K+ cotransporter, and Na+ and K+ leakage, were not changed during pravastatin treatment.

Conclusions

The present data show that cholesterol lowering in hypercholesterolaemic patients may result in a significant decrease in erythrocyte and platelet membrane cholesterol content. These changes in membrane cholesterol are accompanied by an increase in activity of the Na+-K+ pump and a decrease in intra-erythrocyte and intraplatelet Na* concentrations.

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