Targeting platelet aggregation: CD39 gene transfer augments nucleoside triphosphate diphosphohydrolase activity in injured rabbit arteries

Background. CD39, the major endothelial nucleoside triphosphate diphosphohy drolase (NTPDase), plays an important role in local thromboregulation. We h ypothesized that balloon injury (BI) leads to an acute reduction in arteria l NTPDase activity that could be restored by a targeted gene delivery strat egy. Methods. Recombinant adenoviral vectors containing human CD39 (Ad-CD39) or beta -galactosidase (Ad-LacZ) were used. Endothelial (ECs) and smooth muscl e cells (SMCs) were infected in vitro and NTPDase activity measured. New Ze aland white rabbits (N = 28) underwent bilateral iliofemoral artery balloon injury, followed by incubation with Ad-CD39, Ad-LacZ, or vehicle. Explante d vessels were analyzed for NTPDase activity arid localization of CD39 expr ession by immunohistochemistry. Deposition of fluorescent-labeled platelets was studied 3 days after injury and vector treatment. Results. In vitro, Ad-CD39 infection resulted in a greater than 40-fold inc rease in adenosine diphosphatase activity in ECs and a 3-fold increase in S MCs. In vivo, CD39 transgene expression localized to the luminal aspect of Ad-CD39-treated vessels. BI resulted in an acute reduction in vessel wall N TPDase activity (P < .05). Ad-CD39 augmented NTPDase activity when compared with vehicle or Ad-LacZ (P < .05). Platelet deposition on the injured arte rial surface was modest arid not different between Ad-CD39- and Ad-LacZ-tre ated vessels. Conclusions. BI decreases native NTPDase activity, which can be augmented b y adenovirus-mediated gene transfer of CD39. Further studies are required t o determine whether targeted delivery of CD39 could convey thromboprotectiv e properties to an injured vessel.