title: In vivo hepatocyte growth factor gene transfer reduces myocardial ischemia-reperfusion injury through its multiple actions.
abstract: BACKGROUND
  Hepatocyte growth factor (HGF) is reported to protect the heart against ischemia-reperfusion injury. However, whether in vivo adenovirus-mediated HGF gene transfer before ischemia is protective against ischemia-reperfusion and its precise mechanisms are still unknown.
  
  
  RESULTS
  By using a rabbit model of ischemia-reperfusion injury, we demonstrate that HGF gene transfer is cardioprotective through its multiple beneficial actions, such as angiogenesis, Bcl-2 overexpression, and decreasing hydroxyl radicals, deoxyuride-5'-triphosphate biotin nick end labeling (TUNEL)-positive myocytes, and fibrotic area. After HGF gene transfer, the rabbits underwent 30 minutes of coronary occlusion and 30 minutes, 4 hours, 48 hours, and 14 days of reperfusion. The infarct size at 48 hours of reperfusion was significantly reduced in the HGF group (13.4% +/- 2.3%) compared with that in the LacZ group (36.5% +/- 2.0%) and saline group (40.3% +/- 3.2%). At 14 days of reperfusion, HGF gene transfer improved left ventricular ejection fraction and fractional shortening, reduced the fibrotic area, and increased the capillary density in the risk area. At 4 hours of reperfusion, Bcl-2 protein was overexpressed and the incidence of TUNEL-positive myocytes was significantly decreased in the risk area in the HGF group compared with the LacZ and saline groups. The myocardial interstitial 2,5-dihydroxybenzoic acid level, an indicator of hydroxyl radical, increased during 30 minutes of ischemia and 30 minutes of reperfusion in the LacZ and saline groups, and was significantly inhibited in the HGF group.
  
  
  CONCLUSIONS
  HGF gene therapy may be a novel therapeutic strategy against unstable angina pectoris or severe angina pectoris, which may progress to acute myocardial infarction.
authors: Department of Cardiology, Regeneration and Advanced Medical Science, Gifu University, Gifu, Japan.
authors: Xue-Hai
authors: XH
authors: Chen
authors: Shinya
authors: S
authors: Minatoguchi
authors: Kenichiro
authors: K
authors: Kosai
authors: Kentaro
authors: K
authors: Yuge
authors: Tomoyuki
authors: T
authors: Takahashi
authors: Masazumi
authors: M
authors: Arai
authors: Ningyuan
authors: N
authors: Wang
authors: Yu
authors: Y
authors: Misao
authors: Chuanjiang
authors: C
authors: Lu
authors: Hirohito
authors: H
authors: Onogi
authors: Hiroyuki
authors: H
authors: Kobayashi
authors: Shinji
authors: S
authors: Yasuda
authors: Masayasu
authors: M
authors: Ezaki
authors: Hiroaki
authors: H
authors: Ushikoshi
authors: Genzou
authors: G
authors: Takemura
authors: Takako
authors: T
authors: Fujiwara
authors: Hisayoshi
authors: H
authors: Fujiwara
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D017228:Hepatocyte Growth Factor