title: Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats.
abstract: OBJECTIVE
  Hepatocyte growth factor (HGF) is a multi-potent growth factor, which has anti-fibrotic effects for lung injuries. In this study, we investigated whether human HGF gene transfer may attenuate the medial hypertrophy of pulmonary arteries and enhance the ameliorating effect of prostacyclin in monocrotaline (MCT)-induced pulmonary hypertension in rats.
  
  
  RESULTS
  The day before MCT injection, HVJ-liposome complex with the cDNA encoding HGF gene (H group), PGIS gene (P group), and both HGF and PGIS gene (HP group) were transfected to the liver of rats as drug delivery system for the lung. Rats transfected with control vector served as controls (C group). Twenty-eight days after MCT injection, histological examination showed marked thickening of medial wall of pulmonary arteries and right ventricular hypertrophy. Percent medial wall thickness (%WT) of peripheral pulmonary arteries, pressure ratio of the right ventricle (RV) to the left ventricle (LV), and weight ratio of the RV to the LV plus septum were significantly increased in the control. Percent medial wall thickness was significantly ameliorated in H group and HP group in comparison with C group. Pressure and weight ratio of RV to LV was significantly ameliorated in P group and HP group in comparison with C group, and was significantly ameliorated in HP group than P group.
  
  
  CONCLUSIONS
  In vivo gene transfection with HGF gene attenuated the medial hypertrophy of pulmonary arteries and enhanced the ameliorating effect of prostacyclin for pulmonary hypertension in MCT rats. Thus, gene therapy with HGF and PGIS may be a promising strategy for severe pulmonary hypertension.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ono
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Norihide
authors.initials: N
authors.lastname: Fukushima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suhara
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Chieko
authors.initials: C
authors.lastname: Yokoyama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tanabe
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000235:genetics*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D017380:Hypertrophy, Right Ventricular / Q000473:pathology / Q000517:prevention & control; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D016686:Monocrotaline; D009929:Organ Size / Q000502:physiology; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection / Q000379:methods*
chemical_list: D017228:Hepatocyte Growth Factor; D016686:Monocrotaline; D003577:Cytochrome P-450 Enzyme System; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase