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Venous neointimal hyperplasia in polytetrafluoroethylene dialysis grafts
P Roy-Chaudhury1, B S Kelly, M A Miller
1Division of Nephrology, Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0585, USA. prabir.roychaudry@uc.edu
Insights
Venous neointimal hyperplasia (VNH) in dialysis grafts involves macrophages, growth factors like PDGF, bFGF, and VEGF, and angiogenesis. Targeting these may prevent graft failure and reduce healthcare costs.
Area of Science:
- Vascular Biology
- Neointimal Hyperplasia
- Dialysis Access
Background:
- Vascular access dysfunction is a major cause of morbidity and hospitalization in hemodialysis patients.
- Venous neointimal hyperplasia (VNH) in polytetrafluoroethylene (PTFE) grafts leads to stenosis, thrombosis, and graft failure.
- Current therapies for VNH in PTFE grafts are ineffective, incurring significant costs.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying venous neointimal hyperplasia (VNH) in PTFE dialysis grafts.
- To identify key mediators and processes involved in the pathogenesis of VNH.
Main Methods:
- Collected tissue samples from stenotic PTFE graft-vein anastomoses.
- Utilized light microscopy and immunohistochemistry to analyze neointimal hyperplasia.
- Assessed expression of cell types, cytokines (PDGF, bFGF, VEGF), and matrix proteins.
Main Results:
- VNH characterized by smooth muscle cells/myofibroblasts, extracellular matrix accumulation, and angiogenesis.
- An active macrophage layer was present lining the PTFE graft material.
- Growth factors (PDGF, bFGF, VEGF) were expressed by smooth muscle cells and macrophages, and associated with neointimal vessels.
Conclusions:
- Macrophages, specific cytokines (bFGF, PDGF, VEGF), and angiogenesis contribute to VNH pathogenesis in PTFE grafts.
- Targeting these mediators and processes may offer therapeutic strategies.
- Interventions could reduce the substantial human and economic costs of vascular access dysfunction.
Background:
Vascular access dysfunction is the most important cause of morbidity and hospitalization in the hemodialysis population in the United States at a cost of $1 billion per annum. Venous neointimal hyperplasia (VNH) characterized by stenosis and subsequent thrombosis accounts for the overwhelming majority of pathology resulting in polytetrafluoroethylene (PTFE) dialysis graft failure. Despite the magnitude of the problem and the enormity of the cost ($1 billion), there are currently no effective therapies for the prevention or treatment of venous neointimal hyperplasia in PTFE dialysis grafts.
Methods:
Tissue samples were collected from the graft-vein anastomosis of stenotic PTFE grafts during surgical revision. Specimens were graded using standard light microscopy and immunohistochemistry for the magnitude of neointimal 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/myofibroblasts, (2) accumulation of extracellular matrix components, (3) angiogenesis within the neointima and adventitia, and (4) presence of an active macrophage cell layer lining the PTFE graft material. Platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were expressed by smooth muscle cells/myofibroblasts within the venous neointima, by macrophages lining both sides of the 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. Interventions aimed at these specific mediators and processes may be successful in reducing the very significant human and economic costs of vascular access dysfunction.
