Targets for gene therapy of vein grafts.

Poor long-term patency and a lack of suitable systemic pharmacologic therapy for the prevention of vein graft failure have prompted the search for effective local gene therapy. Vein grafts are particularly well suited for gene transfer in the clinic because direct access to vein is available during surgical preparation for grafting. In this review, the available animal models are discussed and a new mouse model is highlighted. Recent advances in gene transfer technology are reviewed, including the use of adeno-associated virus and modified adenoviruses that can prolong in vivo transgene expression for months. Gene therapy is intended to reduce early thrombosis, reduce neointima formation, and prevent atherosclerosis in vein grafts. Promising antithrombotic targets include tissue plasminogen activator and thrombomodulin. Nitric oxide synthase, prostacyclin synthase, and tissue inhibitors of metalloproteinases have been used to reduce neointima formation, and vein graft atheroma remains a challenge for the future.