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



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.



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.
1 Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University , Shanghai, China .
Lei
L
Miao
1 Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University , Shanghai, China .
Xiaoyan
X
Shen
2 University of Exeter Medical School , Exeter, United Kingdom .
Matthew
M
Whiteman
1 Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University , Shanghai, China .
Hong
H
Xin
1 Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University , Shanghai, China .
Yaqi
Y
Shen
1 Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University , Shanghai, China .
Xiaoming
X
Xin
3 Department of Pharmacology, Yoo Loo Lin School of Medicine, National University of Singapore , Singapore, Singapore .
Philip K
PK
Moore
1 Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University , Shanghai, China .|3 Department of Pharmacology, Yoo Loo Lin School of Medicine, National University of Singapore , Singapore, Singapore .|4 School of Pharmacy, Macau University of Science and Technology, Macau .
Yi-Zhun
YZ
Zhu
D000818:Animals; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D006334:Heart Function Tests; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008066:Lipolysis; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality; D032383:Myocytes, Cardiac; D001678:Organelle Biogenesis; D010084:Oxidation-Reduction; D018754:Ventricular Dysfunction / Q000188:drug therapy
D005227:Fatty Acids; D006862:Hydrogen Sulfide