Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients

BackgroundInterventional treatment with atorvastatin lowered the circulating levels of the catalytic core of NADPH oxidase, namely sgp91phox, but the underlying mechanism is still undefined.AimTo test the hypothesis that the inhibitory effect on oxidative stress, induced by Atorvastatin, could be mediated by adiponectin.Methods and resultsWe compared 36 patients with polygenic hypercholesterolemia and 18 healthy subjects. Patients were randomized to either a low-fat diet (Group A) or low-fat diet plus atorvastatin 10 mg/day (Group B) for 30 days. Lower serum adiponectin levels and higher lipid profile, gp91phox serum levels, urinary isoprostanes, platelet oxygen free radicals, characterized patients. After 30 days of treatment, group B showed higher levels of adiponectin which is inversely correlated to reduced levels of sgp91phox, urinary isoprostanes and platelet oxygen free radicals (p < 0.001).In in vitro model, adiponectin dosages between 5 and 10 ng/ml inhibited p47phox translocation to gp91phox and soluble gp91phox cleavage indicating its ability in inhibiting the assembly of NADPH oxidase subunits on cell membrane and in turn the enzymatic system activation.ConclusionThis study provides the first evidence that in patients higher APN serum levels are associated with gp91phox down-regulation. APN-mediated gp91phox reduction could be one of the mechanisms involved in atorvastatin's antioxidant effect.