title: Myocardin-related transcription factor-A-overexpressing bone marrow stem cells protect cardiomyocytes and alleviate cardiac damage in a rat model of acute myocardial infarction.
abstract: Myocardin-related transcription factor-A (MRTF-A) can transduce biomechanical and humoral signals, which can positively modulate cardiac damage induced by acute myocardial infarction (AMI). In the clinic, bone marrow stem cell (BMSC) therapy is being increasingly utilized for AMI; however, the effects of BMSC transplantation remain to be optimized. Therefore, a novel strategy to enhance BMSC‑directed myocardial repair is particularly important. The present study was performed to assess the efficacy of MRTF‑A-overexpressing BMSCs in a rat model of AMI. Primary cardiomyocytes were prepared from neonatal Sprague-Dawley rats and BMSCs were isolated from male Sprague-Dawley rats (aged 8-12 weeks). Annexin V-phycoerythrin/7-actinomycin D staining was used to evaluate BMSC and cardiomyocyte survival after exposure to hydrogen peroxide in vitro. B-cell lymphoma 2 (Bcl-2) protein expression was measured by flow cytometric and western blot analyses. The effects of MRTF-A‑overexpressing BMSCs in a rat model of AMI were investigated by hematoxylin and eosin staining and western blot analysis of Bcl-2 expression in myocardial tissue sections. MRTF-A enhanced the migration of BMSCs, and overexpression of MRTF-A in BMSCs prevented hydrogen peroxide-induced apoptosis in primary cardiomyocytes ex vivo. In addition, co-culture of cardiomyocytes with MRTF‑A-overexpressing BMSCs inhibited hydrogen peroxide-induced apoptosis and the enhanced expression of Bcl-2. Furthermore, in vivo, enhanced cell survival was observed in the MRTF-A-modified BMSC group compared with that in the control group. These observations indicated that MRTF-A-overexpressing BMSCs have the potential to exert cardioprotective effects against hydrogen peroxide-induced injury and that treatment with MRTF‑A‑modified BMSCs is able to reverse cardiac dysfunction after AMI.
authors.affiliation: The Second Affiliated Hospital (Jiande Branch), Department of Cardiology, Zhejiang University School of Medicine, Jiande, Zhejiang 311600, P.R. China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: The Second Affiliated Hospital (Jiande Branch), Department of Cardiology, Zhejiang University School of Medicine, Jiande, Zhejiang 311600, P.R. China.
authors.forename: Jia-Qing
authors.initials: JQ
authors.lastname: Hu
authors.affiliation: The Second Affiliated Hospital (Jiande Branch), Department of Cardiology, Zhejiang University School of Medicine, Jiande, Zhejiang 311600, P.R. China.
authors.forename: Xin-Dong
authors.initials: XD
authors.lastname: Wu
authors.affiliation: The Second Affiliated Hospital (Jiande Branch), Department of Cardiology, Zhejiang University School of Medicine, Jiande, Zhejiang 311600, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The Second Affiliated Hospital (Jiande Branch), Department of Cardiology, Zhejiang University School of Medicine, Jiande, Zhejiang 311600, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D002478:Cells, Cultured; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D014157:Transcription Factors; C557977:myocardin-related transcription factor-A, rat