Abstract 16666: Hydrogen Sulfide Attenuates Ischemic Heart Failure by Suppressing Pro-Apoptotic Cofilin-2
Background: Hydrogen sulfide (H2S) has been shown to protect against ischemic and inflammatory injury following myocardial ischemia/reperfusion via induction of microRNA (miR)-21. We sought to determine whether H2S attenuates ischemic heart failure (HF) and interrogate the role of cofilin-2, a target of miR-21, in this protection.
Methods and Results: Adult male mice underwent myocardial infarction (MI) by permanent coronary artery ligation after baseline echocardiography. The mice were treated with Na2S (100 μg/kg/day; ip) or saline for 28 days. End-diastolic pressure, measured by Millar catheter, was significantly increased (2.1 fold, P<0.05 vs. sham) at 3 days post MI in the saline group, but was attenuated with Na2S (P>0.05 vs. sham). LV fractional shortening decreased significantly at 28 days post-MI in the saline group, but was preserved with Na2S (Fig. A). Moreover, LV infarct scar size, assessed by trichrome staining, was smaller in Na2S group (22.4 ± 2.7%) as compared to control (33.5 ± 2.1%, P<0.05). Apoptotic signaling, measured by Bcl-2/Bax ratio, was significantly increased in the saline group, but was mitigated with Na2S (Fig. B). Survival rate was 2 fold higher in Na2S group compared to control (P<0.05). Proteomic analysis by 2D-gel revealed 46 protein spots with altered expression profiles between saline and Na2S-treated mice at 28 days post MI; and MALDI-TOF/TOF tandem mass spectrometry identified significant changes in miR-21 target, pro-apoptotic cofilin-2. Western blot analysis confirmed a significant increase in cofilin-2 after MI, which was suppressed with Na2S treatment (Fig. C). Western blot analysis further demonstrated a robust increase in myocardial cofilin-2 expression in miR-21 KO mice (Fig. D).
Conclusion: Chronic Na2S treatment after MI preserves LV function and improves survival, possibly through miR-21-mediated suppression of cofilin-2. We propose that H2S donors can be promising therapeutic tools for ischemic HF.
Author Disclosures: K. Nguyen: None. D. Durrant: None. A. Das: None. J. He: None. S. Toldo: None. A. Abbate: Research Grant; Modest; Grifols. Other Research Support; Modest; Swedish Orphan Biovitrum. Research Grant; Significant; Novartis. F.N. Salloum: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.