S2-5 Nrf2 signaling is essential for hydrogen sulfide mediated cardioprotection in the setting of ischemic-induced heart failure

Abstract

Background Therapeutic strategies that increase hydrogen sulfide (H 2 S) bioavailability are known to exert cytoprotective effects in various models of cardiovascular injury. However, the precise mechanism for this protection is not known. Here, we tested the hypothesis that Nuclear-factor-E2-related factor 2 (Nrf2) mediates the cardioprotective effects of H 2 S therapy in the setting of ischemic-induced heart failure. Methods and Results Heart failure was induced by subjecting wild-type (WT) control mice and Nrf2-deficient (Nrf2 KO; C57BL/6 background) mice to 60 min of myocardial ischemia followed by reperfusion. The mice were then followed for a 4-week period, at which time left ventricular dimensions and function were assessed. Nrf2 KO and WT mice received either saline or sodium sulfide (Na 2 S; 100 μg/kg) at the time of reperfusion followed by daily injections for the first 7 days of reperfusion. All groups displayed significant left ventricular dilation, severe cardiac dysfunction, and cardiomyocyte hypertrophy with the Nrf2 KO mice displaying exacerbated dysfunction and hypertrophy compared to the WT mice. Treatment with Na 2 S significantly reduced the degree of dilation and improved left ventricular fraction in the WT mice but failed to improve any of the parameters in the Nrf2 KO mice. Conclusion These findings provide important information that Nrf2 plays a protective role in the setting of heart failure and mediates the cardioprotective effects of H 2 S therapy.