title: Locally overexpressing hepatocyte growth factor prevents post-ischemic heart failure by inhibition of apoptosis via calcineurin-mediated pathway and angiogenesis.
abstract: BACKGROUND
  Myocardial infarction is a significant cause of heart failure. Currently, therapies are limited and novel revascularization methods may play a role. We investigated the effects of hepatocyte growth factor (HGF) expressed by bone marrow-derived mesenchymal stem cells (MSCs) on post-ischemic heart failure.
  
  
  METHODS
  Four weeks after myocardial infarction (MI), Sprague Dawley rats were randomly divided into saline control group, MSC-GFP group, MSC-HGF group, and MSC-HGF+CsA group. After another 4 weeks, hearts were analyzed for ventricular geometry, myocardial function, angiogenesis and endothelial cell density, apoptosis and the expression of calcineurin, Akt, and Bcl-2 protein.
  
  
  RESULTS
  In MSC-HGF group, rats exhibited better LV systolic and diastolic function compared with other groups after 8 weeks of MI. Angiogenesis was significantly enhanced by HGF through inducing proliferation of endothelial cells. The effects of HGF on apoptosis were associated with the expression level of calcineurin protein.
  
  
  CONCLUSIONS
  Our findings suggest that overexpression of HGF improved ischemic cardiac function through angiogenesis and reduction of apoptosis partly mediated by upregulation of calcineurin.
authors.affiliation: Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Guo
authors.forename: Jianguo
authors.initials: J
authors.lastname: He
authors.forename: Junlou
authors.initials: J
authors.lastname: Wu
authors.forename: Long
authors.initials: L
authors.lastname: Yang
authors.forename: Shimo
authors.initials: S
authors.lastname: Dai
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Tan
authors.forename: Lirong
authors.initials: L
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis; D019703:Calcineurin / Q000096:biosynthesis*; D015870:Gene Expression; D006333:Heart Failure / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function
chemical_list: C066855:HGF protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017228:Hepatocyte Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D019703:Calcineurin