title: Reorganization of cytoskeletal proteins and prolonged life expectancy caused by hepatocyte growth factor in a hamster model of late-phase dilated cardiomyopathy.
abstract: OBJECTIVE
  It has been postulated recently that changes in cytoskeletal and sarcolemmal proteins initiate a final common pathway for contractile dysfunction in dilated cardiomyopathy. In ischemic cardiomyopathy, hepatocyte growth factor plays an important role in reorganizing the impaired cytoskeletal proteins in several cell types. We have tested the hypothesis that hepatocyte growth factor might improve life expectancy through modification of the molecular process that contributes to impairment in dilated cardiomyopathy.
  
  
  METHODS
  Adult male 27-week-old BIO TO-2 hamsters, which show moderate cardiac remodeling, were divided into treatment groups that received (1) hemagglutinating virus of Japan liposomes containing human hepatocyte growth factor cDNA (H group), (2) culture medium (C group), or (3) sham operation (S group).
  
  
  RESULTS
  After the operation, echocardiography demonstrated that the enlarged left ventricular end-systolic dimension and decreased fractional shortening were significantly attenuated in the H group compared with the C group. There was significantly less myocardial fibrosis in the H group compared with the C group. Immunohistochemical analysis showed alpha-dystroglycan and alpha- and beta-sarcoglycan expression in the basement membrane beneath the cardiomyocytes in the H group, whereas no expression of these proteins was seen in the C group. The 40-week survival was significantly better in the H group than in the C and S groups.
  
  
  CONCLUSIONS
  An improved survival associated with transient reorganization of the cytoskeletal proteins and reduction in myocardial fibrosis was achieved by hepatocyte growth factor treatment in an adult hamster model of dilated cardiomyopathy. The results suggest a therapeutic potential of hepatocyte growth factor in the treatment of dilated cardiomyopathy.
authors.affiliation: Division of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kondoh
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Norihide
authors.initials: N
authors.lastname: Fukushima
authors.forename: Goro
authors.initials: G
authors.lastname: Matsumiya
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Kitagawa-Sakakida
authors.forename: Imran A
authors.initials: IA
authors.lastname: Memon
authors.forename: Naomasa
authors.initials: N
authors.lastname: Kawaguchi
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D008017:Life Expectancy; D008297:Male; D023421:Models, Animal; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; D017228:Hepatocyte Growth Factor