title: Melatonin facilitates adipose-derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway.
abstract: Mesenchymal stem cells (MSCs)-based therapy provides a promising therapy for the ischemic heart disease (IHD). However, engrafted MSCs are subjected to acute cell death in the ischemic microenvironment, characterized by excessive inflammation and oxidative stress in the host's infarcted myocardium. Melatonin, an indole, which is produced by many organs including pineal gland, has been shown to protect bone marrow MSCs against apoptosis although the mechanism of action remains elusive. Using a murine model of myocardial infarction (MI), this study was designed to evaluate the impact of melatonin on adipose-derived mesenchymal stem cells (AD-MSCs)-based therapy for MI and the underlying mechanism involved with a focus on silent information regulator 1(SIRT1) signaling. Our results demonstrated that melatonin promoted functional survival of AD-MSCs in infarcted heart and provoked a synergetic effect with AD-MSCs to restore heart function. This in vivo effect of melatonin was associated with alleviated inflammation, apoptosis, and oxidative stress in infarcted heart. In vitro studies revealed that melatonin exert cytoprotective effects on AD-MSCs against hypoxia/serum deprivation (H/SD) injury via attenuating inflammation, apoptosis, and oxidative stress. Mechanistically, melatonin enhanced SIRT1 signaling, which was accompanied with the increased expression of anti-apoptotic protein Bcl2, and decreased the expression of Ac-FoxO1, Ac-p53, Ac-NF-ΚB, and Bax. Taken together, our findings indicated that melatonin facilitated AD-MSCs-based therapy in MI, possibly through promoting survival of AD-MSCs via SIRT1 signaling. Our data support the promise of melatonin as a novel strategy to improve MSC-based therapy for IHD, possibly through SIRT1 signaling evocation.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.|Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Congye
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jiangwei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.|Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005260:Female; D008550:Melatonin / Q000494:pharmacology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D008550:Melatonin
keywords: SIRT1 signaling; melatonin; myocardial infarction; oxidative stress; stem cells