title: Gene transfer of human prostacyclin synthase into the liver is effective for the treatment of pulmonary hypertension in rats.
abstract: BACKGROUND
  As one of the future strategies of advanced pulmonary hypertension, intrinsic prostacyclin drug delivery using gene therapy may be useful. We investigated whether transfer of the prostacyclin synthase gene into the liver could ameliorate monocrotaline-induced pulmonary hypertension in rats.
  
  
  METHODS
  The human prostacyclin synthase gene was transfected into the liver of rats with monocrotaline-induced pulmonary hypertension. Hemodynamic indices, blood samples, lung tissues, and survival curves were evaluated between rats receiving the gene and control rats.
  
  
  RESULTS
  High levels of prostacyclin synthase gene expression were found in the hepatocytes of the prostacyclin synthase group. The level of 6-keto-prostaglandin F(1alpha) was significantly higher in the prostacyclin synthase group (prostacyclin synthase, 35.4 +/- 4.4 ng/mL; control, 22.3 +/- 3.3 ng/mL; P =.0436). The right ventricular/femoral artery pressure ratio was significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 0.60 +/- 0.039; control, 0.88 +/- 0.051; P =.0036). The endothelin-1 levels in the lung tissues were significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 10.42 +/- 2.01 pg/mg protein; control, 19.94 +/- 2.82 pg/mg protein; P =.0176). The survival ratio was significantly higher in the prostacyclin synthase group than the control group (P =.0375).
  
  
  CONCLUSIONS
  This drug delivery system using gene transfer can be considered as an alternative for continuous intravenous prostacyclin infusion for pulmonary hypertension.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suhara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Norihide
authors.initials: N
authors.lastname: Fukushima
authors.forename: Koji
authors.initials: K
authors.lastname: Kagisaki
authors.forename: Chieko
authors.initials: C
authors.lastname: Yokoyama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tanabe
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohtake
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006976:Hypertension, Pulmonary / Q000401:mortality / Q000628:therapy*; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003577:Cytochrome P-450 Enzyme System; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase