Targets for gene therapy of vein grafts

Poor long-term patency and a lack of suitable systemic pharmacologic therap y for the prevention of vein graft failure have prompted the search for eff ective local gene therapy. Vein grafts are particularly well suited for gen e transfer in the clinic because direct access to vein is available during surgical preparation for grafting. In this review, the available animal mod els are discussed and a new mouse model is highlighted. Recent advances in gene transfer technology are reviewed, including the use of adeno-associate d virus and modified adenoviruses that can prolong in vivo transgene expres sion for months. Gene therapy is intended to reduce early thrombosis, reduc e neointima formation, and prevent atherosclerosis in vein grafts. Promisin g antithrombotic targets include tissue plasminogen activator and thrombomo dulin. Nitric oxide synthase, prostacyclin synthase, and tissue inhibitors of metalloproteinases have been used to reduce neointima formation, and vei n graft atheroma remains a challenge for the future. (C) 1999 Lippincott Wi lliams & Wilkins, Inc.