title: Postinfarction treatment with an adenoviral vector expressing hepatocyte growth factor relieves chronic left ventricular remodeling and dysfunction in mice.
abstract: BACKGROUND
  Hepatocyte growth factor (HGF) is implicated in tissue regeneration, angiogenesis, and antiapoptosis. However, its chronic effects are undetermined on postinfarction left ventricular (LV) remodeling and heart failure.
  
  
  RESULTS
  In mice, on day 3 after myocardial infarction (MI), adenovirus encoding human HGF (Ad.CAG-HGF) was injected into the hindlimb muscles (n=13). As a control (n=15), LacZ gene was used. A persistent increase in plasma human HGF was confirmed in the treated mice: 1.0+/-0.2 ng/mL 4 weeks later. At 4 weeks after MI, the HGF-treated mice showed improved LV remodeling and dysfunction compared with controls, as indicated by the smaller LV cavity and heart/body weight ratio, greater % fractional shortening and LV +/-dP/dt, and lower LV end-diastolic pressure. The cardiomyocytes near MI, including the papillary muscles and trabeculae, were greatly hypertrophied in the treated mice. The old infarct size was similar between the groups, but the infarct wall was thicker in the treated mice, where the density of noncardiomyocyte cells, including vessels, was greater. Fibrosis of the ventricular wall was significantly reduced in them. Examination of 10-day-old MI revealed no proliferation or apoptosis but showed augmented expression of c-Met/HGF receptor in cardiomyocytes near MI, whereas a greater proliferating activity and smaller apoptotic rate of granulation tissue cells in the HGF-treated hearts was observed compared with controls.
  
  
  CONCLUSIONS
  Postinfarction HGF gene therapy improved LV remodeling and dysfunction through hypertrophy of cardiomyocytes, infarct wall thickening, preservation of vessels, and antifibrosis. These findings imply a novel therapeutic approach against postinfarction heart failure.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu 500-8705, Japan.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Kosai
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yuge
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagano
authors.forename: Masayasu
authors.initials: M
authors.lastname: Esaki
authors.forename: Kazuko
authors.initials: K
authors.lastname: Goto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koda
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kawase
authors.forename: Rumi
authors.initials: R
authors.lastname: Maruyama
authors.forename: Hideshi
authors.initials: H
authors.lastname: Okada
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000235:genetics; D020257:Ventricular Remodeling / Q000187:drug effects / Q000235:genetics
chemical_list: D017228:Hepatocyte Growth Factor; D001973:Bromodeoxyuridine