Atorvastatin Inhibits Advanced Glycation End Products (AGE)-Induced C-Reactive Expression in Hepatoma Cells by Suppressing Reactive Oxygen Species Generation

Recent clinical trials show that atorvastatin, an inhibitor of 3-hydroxy-methylglutaryl coenzyme A, reduces the risk of cardiovascular events and slows the progression of atherosclerosis in patients with coronary artery diseases. Several clinical studies have suggested that atorvastatin has pleiotropic effects. Indeed, atorvastatin reduces C-reactive protein (CRP), an inflammatory biomarker and a powerful predictor of cardiovascular events. However, the molecular mechanism for the anti-inflammatory effect of atorvastatin is not fully understood. Since advanced glycation end products (AGE), the senescent macroprotein derivatives, have been involved in diabetic or non-diabetic atherosclerosis, we investigated here whether and how atorvastatin could inhibit the AGE-induced CRP expression in human cultured hepatoma cells. Atorvastatin dose-dependently inhibited the AGE-induced ROS generation in Hep3B cells. Furthermore, atorvastatin as well as an anti-oxidant N-acetylcysteine, was found to suppress CRP expression in AGE-exposed Hep3B cells at both mRNA and protein levels. These results demonstrate that atorvastatin could block the AGE-signaling to CRP expression through its anti-oxidative property. Our study suggests that atorvastatin may have atheroprotective properties by working as an antiinflammatory agent against AGE in the liver.