PTEN delivery to vein grafts limits intimal hyperplasia and vein graft failure in a canine model. An adenovirus encoding PTEN was used to overexpress PTEN in saphenous veins (SV) prior to aorto-coronary bypass grafting. Ninety days later, grafts were analyzed by angiography (top) and histology (bottom). Compared to saline or empty virus (AdEV) controls, AdPTEN delivery significantly reduced vein disease due to pathological vascular smooth muscle cell growth (from Hata et al, J Thorac Cardiovasc Surg 2005;129:1405-1413). Angiograms show filling defects (yellow arrows), while histology shows significant intimal hyperplasia in control-treated animals.

Current studies are underway to investigate the utility of adeno-associated virus (AAV) (rather than adenovirus) for the delivery of PTEN for the prevention of vein graft disease (funded by a grant from the NHLBI: R21 HL095795 and the Duke Clinical Translational Science Award). In addition to coronary artery bypass grafting, PTEN gene therapy is a viable approach for prevention of intimal hyperplasia in peripheral artery bypass grafting and hemodialysis grafts

PTEN gene therapy for vein graft disease