Venous neointimal hyperplasia in polytetrafluoroethylene dialysis grafts

Background. Vascular access dysfunction is the most important cause of morb idity and hospitalization in the hemodialysis population in the United Stat es at a cost of $1 billion per annum. Venous neointimal hyperplasia (VNH) c haracterized by stenosis and subsequent thrombosis accounts for the overwhe lming majority of pathology resulting in polytetrafluoroethylene (PTFE) dia lysis graft failure. Despite the magnitude of the problem and the enormity of the cost ($1 billion), there are currently no effective therapies for th e prevention or treatment of venous neointimal hyperplasia in PTFE dialysis grafts. Methods. Tissue samples were collected from the graft-vein anastomosis of s tenotic PTFE grafts during surgical revision. Specimens were graded using s tandard light microscopy and immunohistochemistry for the magnitude of neoi ntimal hyperplasia and for the expression of specific cell types, cytokines , and matrix proteins. Results. VNH was characterized by the (1) presence of smooth muscle cells/m yofibroblasts, (2) accumulation of extracellular matrix components, (3) ang iogenesis within the neointima and adventitia, and (4) presence of an activ e macrophage cell layer lining the PTFE graft material. Platelet-derived gr owth factor (PDGF), basic fibroblast growth factor (bFGF), and vascular end othelial growth factor (VEGF) were expressed by smooth muscle cells/myofibr oblasts within the venous neointima, by macrophages lining both sides of th e PTFE graft, and by vessels within the neointima and adventitia. Conclusions. Our results suggest that macrophages, specific cytokines (bFGF , PDGF, and VEGF), and angiogenesis within the neointima and adventitia are likely to contribute to the pathogenesis of VNH in PTFE dialysis grafts. I nterventions aimed at these specific mediators and processes may be success ful in reducing the very significant human and economic costs of vascular a ccess dysfunction.