title: Dual effects of VEGF-B on activating cardiomyocytes and cardiac stem cells to protect the heart against short- and long-term ischemia-reperfusion injury.
abstract: To investigate whether vascular endothelial growth factor B (VEGF-B) improves myocardial survival and cardiac stem cell (CSC) function in the ischemia-reperfusion (I/R) heart and promotes CSC mobilization and angiogenesis.
  
  
  
  One hour after myocardial ischemia and infarction, rats were treated with recombinant human VEGF-B protein following 24 h or 7 days of myocardial reperfusion. Twenty-four hours after myocardial I/R, VEGF-B increased pAkt and Bcl-2 levels, reduced p-p38MAPK, LC3-II/I, beclin-1, CK, CK-MB and cTnt levels, triggered cardiomyocyte protection against I/R-induced autophagy and apoptosis, and contributed to the decrease of infarction size and the improvement of heart function during I/R. Simultaneously, an in vitro hypoxia-reoxygenation (H/R)-induced H9c2 cardiomyocyte injury model was used to mimic I/R injury model in vivo; in this model, VEGF-B decreased LDH release, blocked H/R-induced apoptosis by inhibiting cell autophagy, and these special effects could be abolished by the autophagy inducer, rapamycin. Mechanistically, VEGF-B markedly activated the Akt signaling pathway while slightly inhibiting p38MAPK, leading to the blockade of cell autophagy and thus protecting cardiomyocyte from H/R-induced activation of the intrinsic apoptotic pathway. Seven days after I/R, VEGF-B induced the expression of SDF-1α and HGF, resulting in the massive mobilization and homing of c-Kit positive cells, triggering further angiogenesis and vasculogenesis in the infracted heart and contributing to the improvement of I/R heart function.
  
  
  
  VEGF-B could contribute to a favorable short- and long-term prognosis for I/R via the dual manipulation of cardiomyocytes and CSCs.
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, Hubei Province, China.|Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Lv
authors.affiliation: Department of Cardiology and Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Department of Cardiology and Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology and Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.
authors.forename: Meng-Xi
authors.initials: MX
authors.lastname: Wei
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.
authors.forename: Xian-Yu
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Cardiology and Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiology and Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pharmacology, University of Georgia, Athens, GA, 30602, USA.
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Cardiology and Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China. tangjm416@163.com.|Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei Province, 442000, China. tangjm416@163.com.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Tang
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, Hubei Province, China. hexiaohua@whu.edu.cn.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D006334:Heart Function Tests / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D020107:Troponin T / Q000378:metabolism; D042561:Vascular Endothelial Growth Factor B / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020107:Troponin T; D042561:Vascular Endothelial Growth Factor B; D051028:bcl-2-Associated X Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D003402:Creatine Kinase
keywords: Angiogenesis; Apoptosis; Cardiac stem cells; Mobilization; VEGF-B