Recombinant adenoviral mediated CD39 gene transfer prolongs cardiac xenograft survival

Background. Extracellular ATP and ADP may be important mediators of vascula r inflammation and thrombosis. Nucleoside triphosphate diphosphohydrolase ( NTPDase or CD39) is a vascular ectoenzyme that hydrolyses ATP and ADP; howe ver, this activity is lost during reperfusion injury. We show that the supp lementation of NTPDase activity within xenograft vasculature using CD39 rec ombinant adenoviruses (AdCD39) has protective effects in vivo. Methods. Recombinant adenoviruses containing human CD39 or P-galactosidase (Adp-gal) encoding genes were constructed. Hartley guinea pig coronary arte ries 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. Immun ohistological examination of AdCD39-infected grafts confirmed successful CD 39 gene transfer into the endocardium and macrovasculature. Expression of C D39 modestly prolonged graft survival (90.2+/-5.4 hr, mean+/-SD, n=5) when compared with Ad beta-gal-infected grafts (67.4+/-5.4 hr, P<0.005) and perf usion 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.