Abstract 20085: Inhibition of Hdac Induces Protective Effects Against Diabetic Cardiomyopathy

Abstract

Background: It is known that inhibition of histone deacetylases (HDACs) protects the heart against ischemic injury. However, it remains unknown whether HDAC inhibition produces the cardioprotective effect in the diabetic heart. Objective: We sought to determine whether HDAC inhibition preserves cardiac performance and suppresses cardiac remodeling in diabetic cardiomyopathy. Methods: Adult ICR male mice received an intraperitoneal injection (i.p.) of streptozotocin (STZ, 200mg/kg) to establish the diabetic model. Once hyperglycemia was confirmed, diabetic mice received sodium butyrate, a specific HDAC inhibitor (1%) in drinking water on a daily basis. Myocardial function was assessed by echocardiography. Cardiac hypertrophy, fibrosis, and myocyte death were evaluated by histological analysis. Western blot was employed to determine the proteins of signaling pathways. Results: Left ventricular function was depressed in diabetic mice as compared with control group. HDAC inhibition resulted in an improvement in cardiac function in STZ-injected mice (Table1). Likewise, HDAC inhibition attenuates cardiac hypertrophy, as evidenced by a reduced heart/tibia ratio and areas of cardiomyocytes. Additionally, sodium butyrate reduced interstitial fibrosis and apoptosis, but increased angiogenesis in diabetic myocardium. Notably, glucose transporter type 1 and 4 (GLUT1, GLUT4) and superoxide dismutase (SOD 1) were elevated following HDAC inhibition in the diabetic myocardium. GLUT1 acetylation was increased in diabetic myocardium following HDAC inhibition. Conclusion: HDAC inhibition plays a critical role to reduce cardiac damage in diabetic mice.