Hydrogen Sulfide Therapy Suppresses Cofilin-2 and Attenuates Ischemic Heart Failure in a Mouse Model of Myocardial Infarction.

ABSTRACT:

Aims

Hydrogen sulfide (H₂S) protects against ischemic and inflammatory injury following myocardial ischemia via induction of microRNA (miR)-21. We sought to determine whether H₂S attenuates ischemic heart failure with reduced ejection fraction (HFrEF) and interrogate the role of cofilin-2, a target of miR-21, in this protective process.

Methods and results

Adult male mice underwent myocardial infarction (MI) by coronary artery ligation after baseline echocardiography. Following MI, mice were treated with Na₂S (100 μg/kg/day; intraperitoneal [IP]) or saline up to 28 days. End-diastolic pressure, measured by Millar catheter, was significantly increased (P < .05 vs sham) at 3 days post-MI in the saline group, which was attenuated with Na₂S. Left ventricular (LV) fractional shortening decreased significantly at 28 days post-MI in the saline group but was preserved with Na₂S and LV infarct scar size was smaller in Na₂S group as compared to control. Apoptotic signaling, measured by Bcl-2/Bax ratio, was significantly increased in the saline group but was mitigated with Na₂S. Survival rate was 2-fold higher in Na₂S group compared to saline control (P < .05). Proteomic analysis and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (TOF)/TOF tandem mass spectrometry identified significant changes in proapoptotic cofilin-2 expression, a specific target of miR-21, between saline- and sodium sulfide -treated mice at 28 days post-MI. Western blot analysis confirmed a significant increase in cofilin-2 after MI, which was suppressed with Na₂S treatment. Chronic Na₂S treatment also attenuated inflammasome formation and activation leading to reduction of maladaptive signaling.

Conclusion

Na₂S treatment after MI preserves LV function and improves survival through attenuation of inflammasome-mediated adverse remodeling. We propose H₂S donors as promising therapeutic tools for ischemic HFrEF.

SUBMITTER: Nguyen K 

PROVIDER: S-EPMC7365756 | biostudies-literature |

REPOSITORIES: biostudies-literature