Hydrogen Sulfide Mitigates Myocardial Infarction via Promotion of Mitochondrial Biogenesis-Dependent M2 Polarization of Macrophages

Abstract

Aims: Macrophages are of key importance for tissue repair after myocardial infarction (MI). Hydrogen sulfide (H₂S) has been shown to exert cardioprotective effects in MI. However, the mechanisms by which H₂S modulates cardiac remodeling and repair post-MI remain to be clarified. Results: In our current study, we showed that H₂S supplementation ameliorated pathological remodeling and dysfunction post-MI in wild-type (WT) and CSE KO mice, resulting in decreased infarct size and mortality, accompanied by an increase in the number of M2-polarized macrophages at the early stage of MI. Strikingly, adoptive transfer of NaHS-treated bone marrow-derived macrophages into WT and CSE KO mice with depleted macrophages also ameliorated MI-induced cardiac functional deterioration. Further mechanistic studies demonstrated that NaHS-induced M2 polarization was achieved by enhanced mitochondrial biogenesis and fatty acid oxidation. Innovation and Conclusion: Our study shows (for the first time) that H₂S may have the potential as a therapeutic agent for MI via promotion of M2 macrophage polarization. Rebound Track: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16:293–296, 2012) with the following serving as open reviewers: Hideo Kimura, Chaoshu Tang, Xiaoli Tian, and Kenneth Olson. Antioxid. Redox Signal. 25, 268–281.