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 fluidity. Changes in fluidity have important consequences for membrane function. Treatment of hypercholesterolaemia could therefore affect membrane 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 membrane enzyme NADPH oxidase. Blood was obtained from 12 hypercholesterolaemic patients before, and 6 weeks after, treatment with simvastatin, and from 20 normolipidaemic subjects. Cell cholesterol was in the unesterified from indicating that it was membrane-associated. Pre-treatment mean cell cholesterol concentration in the hyperlipidaemics was higher (P < 0.05) than in the normolipidaemics [4.19 fmol/cell, 95% confidence 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 and there was a correlation (R(s) = 0.61, P < 0.05) between the reductions in cell cholesterol and lag phase.
Day
A P
AP
Department of Chemical Pathology, Bristol Royal Infirmary, UK.
Bellavia
S
S
Jones
O T
OT
Stansbie
D
D
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000097:blood; D008875:Middle Aged; D019255:NADPH Oxidases / Q000097:blood*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D019821:Simvastatin
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008563:Membrane Lipids; D008148:Lovastatin; D019821:Simvastatin; D019255:NADPH Oxidases