EFFECT OF SIMVASTATIN THERAPY ON CELL-MEMBRANE CHOLESTEROL CONTENT AND MEMBRANE-FUNCTION AS ASSESSED BY POLYMORPHONUCLEAR CELL NADPH OXIDASE ACTIVITY

Cell membrane cholesterol is an important determinant of membrane flui dity. Changes in fluidity have important consequences for membrane fun ction. Treatment of hypercholesterolaemia could therefore affect membr ane function by reducing cell membrane cholesterol levels. The aim of this study was to determine whether treatment with simvastatin affects membrane cholesterol and the activity of the polymorphonuclear cell m embrane enzyme NADPH oxidase. Blood was obtained from 12 hypercholeste rolaemic patients before, and 6 weeks after, treatment with simvastati n, and from 20 normolipidaemic subjects. Cell cholesterol was in the u nesterified form indicating that it was membrane-associated. Pretreatm ent mean cell cholesterol concentration in the hyperlipidaemics was hi gher (P < 0.05) than in the normolipidaemics [4.19 fmol/cell, 95% conf idence interval (CI) 3.38-5.05 versus 3.10 fmol/cell, 95% CI 2.58-3.61 ]. There was a strong correlation between cell cholesterol content and NADPH oxidase lag phase (R-s = 0.76, P < 0.01). Cell cholesterol fell to 3.52 fmol/cell (95% CI 2.77-4.28, P < 0.05) following treatment an d there was a correlation (R-s = 0.61, P < 0.05) between the reduction s in cell cholesterol and lag phase.