Abstract 15911: Essential Role of MicroRNA-21 in Hydrogen Sulfide-induced Protection against Myocardial Ischemia/Reperfusion Injury
Background: Hydrogen sulfide (H2S) protects against myocardial ischemia/reperfusion (I/R) injury through activation of Akt. Since Ser473/Thr308 phosphorylation of Akt induces microRNA (miR-21) in the heart, we speculated that H2S would also induce myocardial miR-21 and protect against I/R injury as well.
Methods and Results: Adult C57BL wild-type or miR-21 knock-out (KO) mice were treated with vehicle (saline) or the H2S donor, Na2S, (100 μg/kg, ip) 1 h before 30 min ischemia followed by 24 h reperfusion. To test reperfusion therapy with H2S, Na2S (100 μg/kg, iv) or vehicle were administered at the onset of reperfusion in another subset of mice. After reperfusion, LV function was monitored by echocardiography and infarct size (IS) was measured by TTC staining. MiR-21 expression was assessed with qPCR 1h after treatment. Na2S increased miR-21 in wild-type mice (2.8-Fold, P<0.05 vs. control). Infarct size was reduced with Na2S when given as a preconditioning mimetic (Fig. A) or as reperfusion therapy (Fig. B) compared to vehicle. The infarct-limiting effect of Na2S was abolished in the miR-21 KO mice in both treatment scenarios. Moreover, Na2S preserved fractional shortening (FS: 30±2.8%) as compared to the control (17±1.8%, P<0.05) when administered prior to I/R and also at the onset of reperfusion (27±2.5%) as compared to control (18±1.8%, P<0.05). The functional recovery observed with Na2S was absent in miR-21 KO mice in both cases (FS: 14±2.1% and 17±1%, respectively).
Conclusion: : Hydrogen sulfide reduces myocardial infarct size and preserves LV function 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 and other cardiovascular diseases.
- © 2013 by American Heart Association, Inc.