title: Gene transfer of extracellular superoxide dismutase ameliorates pulmonary hypertension in rats.
abstract: BACKGROUND
  Pulmonary hypertension (PH) is a life-threatening disease, characterized by vascular remodeling and vasoconstriction. Evidence suggests that oxidative stress may contribute to the pathogenesis and/or development of PH.
  
  
  OBJECTIVE
  In the present study, we examined whether intratracheal gene transfer of human extracellular superoxide dismutase (EC-SOD) could ameliorate monocrotaline (MCT)-induced PH in rats.
  
  
  METHODS
  MCT-injected rats were intratracheally administered vehicle (MCT group) or an adenovirus encoding beta-galactosidase (Adbetagal group) or human EC-SOD (AdEC-SOD group).
  
  
  RESULTS
  After intratracheal gene transfer, EC-SOD was successfully expressed in lung tissue, bronchoalveolar lavage fluid, and plasma. Twenty-eight days after MCT injection, right ventricular systolic pressure and the weight ratio of the right ventricle to the left ventricle plus septum were significantly lower in the AdEC-SOD group (42.50 +/- 1.46 mm Hg and 0.453 +/- 0.029, respectively) than in the MCT group (59.89 +/- 1.61 mm Hg and 0.636 +/- 0.022, respectively) or the Adbetagal group (61.50 +/- 2.61 mm Hg and 0.653 +/- 0.038, respectively). Moreover, vascular remodeling and proliferation of vascular smooth muscle cells in pulmonary arteries were markedly suppressed in the AdEC-SOD group. Importantly, 8-isoprostane in lung tissue was also significantly reduced in the AdEC-SOD group.
  
  
  CONCLUSIONS
  EC-SOD overexpression to the lung ameliorated MCT-induced PH in rats. We suggest that EC-SOD may act as an antioxidant in PH and that increased oxidative stress may be important in the pathogenesis of MCT-induced PH.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku 807-8555, Kitakyushu, Japan. h-tasaki@med.uoeh-u.ac.jp
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kamezaki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tasaki
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yamashita
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Koide
authors.forename: Sei
authors.initials: S
authors.lastname: Nakata
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okazaki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Otsuji
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006339:Heart Rate; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008168:Lung / Q000378:metabolism; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D016686:Monocrotaline; D013482:Superoxide Dismutase; D001616:beta-Galactosidase