Hydrogen Sulfide Mitigates Myocardial Infarction via Promotion of Mitochondrial Biogenesis-Dependent M2 Polarization of Macrophages.
Antioxidants and Redox Signaling
Mary Ann Liebert
This is the author accepted manuscript. The final version is available from Mary Ann Liebert via the DOI in this record.
Reason for embargo
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 H2S supplementation ameliorated pathological remodeling and dysfunction post-MI in 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 (BMMs) 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 (FAO). 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.
This work was funded by the Key Program of National Nature Science Foundation of China (No.81330080) and the Key Program of Shanghai Committee of Science and Technology in China (No. 14JC1401100).
Online : June 13, 2016