Increased Superoxide Anion Production by Platelets in Hypercholesterolemic Patients

Abstract

SummaryThe purpose of this study was to investigate the relationship between hypercholesterolemia and superoxide anion production.Experimental studies demonstrated that hypercholesterolemia is associated with enhanced cellular superoxide anion (O2 −) production. Aim of the study was to assess whether the same phenomenon occurs in humans.Lipid profile and platelet O2 − production were measured in 28 patients with hypercholesterolemia, compared with 25 age- and sexmatched healthy subjects, and in 21 out of the 28 patients after 8-week treatment with 10 mg/day atorvastatin (a HMGCoA reductase inhibitor). In order to assess the mechanism by which LDL cholesterol interferes with platelet production of O2 −, human platelets were incubated with LDL cholesterol in the presence of either an inhibitor of the phospholipaseA2 enzyme, AACOCF3, or an inhibitor of NADH/NADPH oxidases, DPI.O2 − platelet generation was significantly higher (p <0.001) and significantly related to LDL cholesterol (p < 0.001 ) in patients as compared to controls. 8-week treatment with 10 mg/day atorvastatin significantly reduced both LDL cholesterol and O2 − platelet production. This effect was partially related to the cholesterol-lowering, in that three days of treatment with atorvastatin significantly decreased platelet O2 − production, while no significant change in LDL-cholesterol levels was observed. Platelets incubated with LDL cholesterol showed O2 − release by atorvastatin is partially related to cholesterol lowering effect, suggesting that other mechanisms could be responsible for the antioxidant activity of the drug.