Atorvastatin, Valsartan, and N-Acetylcysteine Prevent Cardiac Hypertrophy and Overexpression of Myocardin in Pressure-Overloaded Rat Heart

Background: The use of statin has emerged as a beneficial treatment for cardiac hypertrophy. Myocardin, a cardiac restricted gene, is up-regulated in the hypertrophic myocardium. However, the effect of statin on myocardin expression due to pressure overloaded cardiac hypertrophy is not well understood. Methods: To evaluate the effect of statin on myocardin expression and cardiac hypertrophy, infrarenal aortic banding was performed for 4 weeks in adult Sprague-Dawley rats to induce cardiac hypertrophy. Atorvastatin (30 mg/kg), valsartan (30 mg/kg), N-acetylcysteine (NAC; 250 mg/kg), and the above three agents combined were given daily after surgery. Results: After aortic banding for 4 weeks, the heart weight, the ratio of heart/body weight, and mean arterial pressure (MAP) increased significantly. However, echocardiography showed concentric hypertrophy after aortic banding. Elevated MAP and increased wall thickness and heart weight were reversed after treatment with atorvastatin, valsartan, NAC, and a combination of the three agents. Myocardin, myosin heavy chain (MHC), brain natriuretic peptide (BNP) proteins, myocardin mRNA, angiotensin II (AngII), and superoxide dismutase (SOD) expressions were up-regulated in the banding group, which were inhibited by atorvastatin, valsartan, NAC, and the three agents combined. Increased immunohistochemical labelings of myocardin and MHC in the ventricular myocardium were observed in the banding group, and again atorvastatin, valsartan, or NAC reversed the labelings. Conclusion: Myocardin, MHC, BNP proteins, myocardin mRNA, AngII, and SOD expressions were up-regulated in the rat model of pressure-overloaded cardiac hypertrophy. Treatment with atorvastatin, valsartan, NAC, or three agents put together is associated with a reversal of abnormal regulation of myocardin in the hypertrophic myocardium.