Abstract 13513: Hydrogen Sulfide Preconditions the Diabetic Heart by Inactivating the Transcription Repressor Bach1 and Activating Nrf2 Signaling
Background: Hydrogen sulfide (H2S) is an endogenous signaling molecule with cardioprotective effects. Here we sought to examine if H2S preconditioning could provide cardioprotection in the setting of diabetes.
Methods and Results: Diabetic mice (db/db) were administered daily doses of saline (vehicle) or sodium sulfide (Na2S, 100 µg/kg) for 7 days. Mice were then subjected to 30 minutes of left coronary artery occlusion (LCA) followed by 2 hours of reperfusion at which time the extent of myocardial injury was evaluated. Na2S preconditioning decreased infarct size (INF) relative to the area-at-risk (AAR) by 34% compared to the vehicle treated animals and decreased the level of circulating troponin-I by 62%. The reduction in myocardial injury was also associated with a reduction in oxidative stress. In an effort to evaluate the signaling mechanism responsible for the observed cardioprotection, mice were administered (via tail vein) vehicle or Na2S for 7 days. Heart tissue was then excised and processed for Western blot analysis. Treatment with Na2S increased the nuclear localization of the transcription factor Nrf2 and increased the expression of its downstream target, heme oxygenase (HO)-1. Further studies investigating Bach1, a known repressor of HO-1 transcription, revealed a down regulation of its nuclear expression in the Na2S treated group compared to the vehicle treated group.
Conclusion: This data suggests, that the administration of exogenous Na2S prior to ischemia/reperfusion injury may induce cardioprotection in the diabetic heart by removing Bach1 from the nucleus, which allows for the activation of Nrf2 signaling.
- © 2011 by American Heart Association, Inc.