Gene therapy for vein grafts.

Bypass vein graft failure represents the greatest limitation to the current surgical therapy of myocardial and lower extremity ischemia. Elucidation of the molecular and cellular biology of neointimal hyperplasia and subsequent vein graft atherosclerosis has formed a basis for the design and implementation of gene-based therapies to prevent vein graft disease. Manipulation of the genetic regulation of vascular cell cycle progression has been shown to effectively redirect vein graft biology away from neointimal disease and toward medial hypertrophy as a more adaptive form of remodeling in response to stresses of the arterial circulation, and has prevented experimental graft atherosclerosis. Early clinical experience suggests that this approach may provide an early avenue for translation of such a gene-based therapy in humans. Other experimental gene transfer strategies have also been explored in animal models of vein grafts, which may be particularly well suited to the application of genetic manipulation given the direct access to the tissue at the time of disease initiation.