Abstract 990: Long-term Treatment With Resveratrol Restores Streptozotocin Induced Decline In Cardiac Function and Sarcoplasmic Reticulum Calcium ATPase Expression
Background: Diabetic cardiomyopathy, characterized by impaired cardiac contractility, develops independent of vascular disease. An important contributor to diastolic dysfunction in the diabetic heart is the reduced activity of sarcoplasmic reticulum calcium pump (SERCA2a). Over expression of SERCA2a alone in transgenic mice could protect diabetic hearts from severe contractile dysfunction. Resveratrol (Res) is a well-characterized grape polyphenol that has exhibited a multitude of cardioprotective properties in vitro and in vivo including antiarrythmic, anti-oxidant, anti-ischemic and anti-hypertrophic effects. Its role in diabetic cardiomyopathy has never been studied.
Objectives: We tested the hypothesis that Resveratrol provides cardioprotection in diabetic cardiomyopathy through improvement in SERCA2a expression and contractile function of the diabetic heart.
Methods and Results: Diabetes was induced in adult CD 1 mice by streptozotocin (in citrate saline pH 4.5, 150 mg /kg i.p.). Mice demonstrating more than 400 mg /dL blood glucose levels were considered diabetic (DM group), vehicle injected animals served as controls (C group). Half of the animals from each group were fed with protein rich purina chow enriched with Res (0.067%, ResDM and ResC groups) and three months later left ventricular function was analyzed in isolated heart preparation. As compared to controls, DM hearts showed a significant reduction in heart weight, body weight and heart weight to tibia length ratio. The expression of SIRT1, an effector of Res was also decreased by 60% in DM hearts. A significant improvement was noted in these parameters in ResDM group. In DM hearts, systolic pressure was decreased by 30% and maximum speed of relaxation (-dP/dt) by 45%. The contractile impairment in diabetic hearts was accompanied by 3-fold decline in SERCA2a protein. In ResDM group, the diastolic and systolic functions were similar to C and ResC groups and SERCA 2a expression was 2.5-fold higher as compared to DM group. Reserveratrol alone had no effect on these parameters.
Conclusions and Implications: Our results indicate that resveratrol improves cardiac function involving SERCA2a expression in diabetic hearts and provides cardioprotection in diabetic cardiomyopathy.