title: Recombinant adenoviral mediated CD39 gene transfer prolongs cardiac xenograft survival.
abstract: BACKGROUND
  Extracellular ATP and ADP may be important mediators of vascular inflammation and thrombosis. Nucleoside triphosphate diphosphohydrolase (NTPDase or CD39) is a vascular ectoenzyme that hydrolyses ATP and ADP; however, this activity is lost during reperfusion injury. We show that the supplementation of NTPDase activity within xenograft vasculature using CD39 recombinant adenoviruses (AdCD39) has protective effects in vivo.
  
  
  METHODS
  Recombinant adenoviruses containing human CD39 or beta-galactosidase (Adbeta-gal) encoding genes were constructed. Hartley guinea pig coronary arteries were perfused ex vivo with University of Wisconsin solution containing 10(9) plaque-forming units of the recombinant adenovirus. Infected grafts were then implanted in the abdomen of complement depleted Lewis rats.
  
  
  RESULTS
  NTPDase activities decreased in all grafts within the first 24 hr and subsequently recovered only in those hearts infected with AdCD39. Immunohistological examination of AdCD39-infected grafts confirmed successful CD39 gene transfer into the endocardium and macrovasculature. Expression of CD39 modestly prolonged graft survival (90.2+/-5.4 hr, mean+/-SD, n=5) when compared with Adbeta-gal-infected grafts (67.4+/-5.4 hr, P<0.005) and perfusion controls (66.4+/-5.2 hr; P<0.005).
  
  
  CONCLUSIONS
  Recombinant adenoviral infection can induce expression of CD39 within cardiac xenografts and provide survival benefits in vivo. Our data show that ex vivo infection by recombinant adenovirus vectors can result in vascular expression of a potential therapeutic agent.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: M
authors.initials: M
authors.lastname: Imai
authors.forename: K
authors.initials: K
authors.lastname: Takigami
authors.forename: O
authors.initials: O
authors.lastname: Guckelberger
authors.forename: E
authors.initials: E
authors.lastname: Kaczmarek
authors.forename: E
authors.initials: E
authors.lastname: Csizmadia
authors.forename: F H
authors.initials: FH
authors.lastname: Bach
authors.forename: S C
authors.initials: SC
authors.lastname: Robson
mesh_terms: D000251:Adenosine Triphosphatases; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001081:Apyrase / Q000378:metabolism; D015153:Blotting, Western; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000276:immunology*; D006085:Graft Survival / Q000235:genetics; D006168:Guinea Pigs; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008297:Male; D051381:Rats; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen