Increased superoxide anion production by platelets in hypercholesterolemic patients

Objectives: The purpose of this study was to investigate the relationship between hypercholesterolemia and Superoxide anion production. Background: Experimental Studies demonstrated that hypercholesterolemia is associated with enhanced cellular Superoxide anion (O-2(-)) production. Aim of the study was to assess whether the same phenomenon occurs in humans. Methods: Lipid profile and platelet O-2(-) production Acre measured in 28 patients with hypercholesterolemia, compared with 25 age- and sex-matched 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 kith platelet production of O-2(-), 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. Results: O-2(-) platelet generation was significantly higher (p<0.001) and significantly related to LDL cholesterol (p<0.001) in patient,, as Compared to controls. 8-keek treatment with 10 mg/day atorvastatin significantly reduced both LDL cholesterol and O-2(-) platelet production. This effect was partially related to the cholesterol-lowering, in that three days of treatment with atorvastatin significantly decreased platelet O-2(-) production, While no significant change in LDL-cholesterol levels was observed. Platelets incubated kith LDL cholesterol showed an increased O-2(-) production, which as significantly inhibited by, AACOCF3 (-78%) and DPI (-56%). Conclusions: LDL cholesterol increases platelet O-2(-) production by activating PLA2 and NADH/NADPH enzymes. Inhibition of platelet O-2(-) release by atorvastatin is partially related to cholesterol lowering effect, suggesting that other mechanisms could he responsible for the antioxidant activity of the drug.