title: Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart.
abstract: BACKGROUND
  Hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, plays a role as organotrophic factor for regeneration of various organs. HGF has an angiogenic activity and exhibits a potent antiapoptotic activity in several types of cells. Although HGF and the c-Met/HGF receptor are expressed in the heart, the role of HGF in the heart has remained unknown.
  
  
  METHODS
  After we analyzed changes in expression of endogenous HGF and c-Met mRNA levels in the rat left ventricle after myocardial infarction, the human HGF gene in hemagglutinating virus of Japan (HVJ)-liposome was transfected into the normal whole rat heart. Three days after transfection, the heart was subjected to global warm ischemia and subsequent reperfusion, followed by assessment of its cardiac functions.
  
  
  RESULTS
  Both HGF and c-Met/HGF receptor mRNAs were expressed in adult rat heart, and c-Met/HGF receptor mRNA was upregulated in response to myocardial infarction. HGF-transfected heart showed significant increase of human HGF protein level in the heart. Cardiac functions in terms of the left ventricular developed pressure, maximum dp/dt, and pressure rate product in hearts with HGF gene transfection were significantly superior to those in control hearts. In addition, leakage of creatine phosphokinase in the coronary artery effluent in hearts with HGF gene transfection was significantly lower than that in control hearts.
  
  
  CONCLUSIONS
  These data indicated that both HGF and c-Met/HGF receptor mRNAs were upregulated in response to myocardial ischemic injury, and that HGF is likely to have a cytoprotective effect on cardiac tissue, presumably through the c-Met/HGF receptor.
authors.affiliation: First Department of Surgery, Biomedical Research Center, Osaka University Medical School, Suita, Japan. hueda@surg1.med.osaka-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Ueda
authors.forename: Y
authors.initials: Y
authors.lastname: Sawa
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Kitagawa-Sakakida
authors.forename: Y
authors.initials: Y
authors.lastname: Kawahira
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneda
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met