Novel Strategies for the Prevention of Bypass Graft Failure
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Bypass vein graft disease remains a significant limitation to the care of millions of patients with ischemic disease of the heart and lower extremities. The pathogenesis of this rapid, aggressive, occlusive disease lies in the remodeling response of the grafts themselves to the new arterial environment. As such, the molecular and cellular biology of neointimal hyperplasia provides a unique opportunity for cardiovascular researchers to more closely model a human clinical entity from its inception to the development of advanced disease. Recent years have therefore seen a broad new array of possible interventions for vein graft disease based on a sophisticated translation of genetic and molecular science. One of these applications, E2F decoys, has already progressed to phase III clinical studies, and many others will likely follow as the tools for therapeutic translation continue to improve. These include both gene transfer and gene blockade strategies.
KeywordsVascular Smooth Muscle Cell Vein Graft Neointimal Hyperplasia Neointimal Formation Vascular Smooth Muscle Cell Proliferation
The author has a financial interest in Corgentech Inc., which owns the rights to and is leading the clinical development of E2F decoy treatment of bypass vein grafts.
- 2.Campeau L, Enjalbert M, Lesperance J, et al. The relation of risk factors to the development of atherosclerosis in saphenous vein bypass grafts and the progression of diseasein the native circulation: a study 10 years after aortocoronary bypass surgery. N Engl J Med 1984; 311: 1329–34PubMedCrossRefGoogle Scholar
- 4.Reardon MJ, Conklin LD, Reardon PR, et al. Coronary artery bypass conduits: review of current status. J Cardiovasc Surg 1997; 97: 916–31Google Scholar
- 37.Grube E, Felderhoff T, Fitzgerald PJ, et al. Genetic manipulation of human coronary artery bypass grafts with E2F decoy (GT003) reduces clinical graft failure: results of the randomized, controlled PREVENT II trial. Late-breaking Clinical Trials Session, American Heart Association Scientific Sessions; 2001 Nov 12; Anaheim, CaliforniaGoogle Scholar
- 47.Ohta S, Komori K, Yonemitsu Y, et al. Intraluminal gene transfer of endothelial cell-nitric oxide synthase suppresses intimai hyperplasia of vein grafts in cholesterol-fed rabbit: a limited biological effect as a result of the loss of medial smooth muscle cells. Surgery 2002; 131: 644–53PubMedCrossRefGoogle Scholar
- 54.Angelini GD, Lloyd C, Bush R, et al. An external, oversized, porous polyester stent reduces vein graft neointima formation, cholesterol concentration, and vascular cell adhesion molecule 1 expression in cholesterol-fed pigs. J Thorac Cardiovasc Surg 2002 Nov; 124(5): 950–6PubMedCrossRefGoogle Scholar