Atorvastatin Inhibits gp91 phox Circulating Levels in Patients With Hypercholesterolemia

Abstract

Objective— The inhibition of oxidative stress is among the most relevant pleiotropic effects of statins. The mechanism by which statins exert their antioxidant effect in vivo is still undefined. NADPH oxidase is among the most important sources of reactive oxygen species involved in atherosclerotic disease. Methods/Results— We developed an ELISA to evaluate serum levels of soluble-gp91 ^phox , the catalytic core of phagocyte NADPH oxidase. In a cross-sectional study performed in 30 hypercholesterolemic patients and in 20 controls, serum soluble-gp91 ^phox and urinary isoprostane, a marker of oxidative stress, were measured. The 2 variables were also measured in hypercholesterolemic patients, randomized to diet (n=15), or diet plus atorvastatin (10 mg daily, n=15) and followed for 30 days. Compared to controls, hypercholesterolemic patients had higher and significantly correlated ( R =0.71; P phox ( P P phox (−33%, P P P Conclusion— Our study demonstrates that statins exert an antioxidant effect via inhibition of soluble gp91 ^phox expression.