MicroRNA‐21 mediates hydrogen sulfide‐induced protection against ischemia/reperfusion injury in diabetic heart (1080.6)

Abstract

Background: Hydrogen sulfide (H2S) protects against myocardial ischemia/reperfusion (I/R) and inflammatory injury in mice via induction of microRNA (miR)-21. Since the diabetic heart is non-compliant with most known cardioprotective strategies, we tested whether H2S would also induce miR-21 in the diabetic heart and protect against I/R injury. Methods and Results: Adult db/db mice were treated with vehicle (saline) or the H2S donor, Na2S, (100 µg/kg, iv) at the end of 30 min. of regional ischemia prior to reperfusion for 24 h. After reperfusion, left ventricular function was assessed by echocardiography and infarct size (IS) was measured by TTC staining. Mir-21 expression was assessed by qPCR. Na2S increased miR-21 in db/db mice (5.3-Fold, P<0.005 vs. control) and reduced IS (34±2%) as compared to control db/db mice (68±3%). To test the role of miR-21 in infarct reduction, adult C57BL or miR-21 KO mice were challenged with streptozotocin (STZ; 150 mg/kg, ip) to induce diabetes 4 weeks prior to subjecting them to I/R injury. Na2S reduced IS in STZ-C57BL mice, but not in STZ-miR-21 KO mice (Figure). Moreover, Na2S preserved fractional shortening (FS: 26±3%) post myocardial infarction in STZ-C57BL mice as compared to saline-treated STZ-C57BL mice (16±2%, P<0.05), but not in miR-21 KO-STZ mice (FS: 14±2%). Conclusion: Hydrogen sulfide reduces infarct size and preserves function in the post ischemic diabetic heart through miR-21-dependent pathway. We propose that H2S might be a novel strategy to up-regulate miR-21 for its therapeutic use against I/R injury in diabetics. Grant Funding Source: This research was funded by AHA (10SDG3770011) and VCU PRQF to FNS.