title: Venous neointimal hyperplasia in polytetrafluoroethylene dialysis grafts.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0585, USA. prabir.roychaudry@uc.edu
authors.forename: P
authors.initials: P
authors.lastname: Roy-Chaudhury
authors.forename: B S
authors.initials: BS
authors.lastname: Kelly
authors.forename: M A
authors.initials: MA
authors.lastname: Miller
authors.forename: A
authors.initials: A
authors.lastname: Reaves
authors.forename: J
authors.initials: J
authors.lastname: Armstrong
authors.forename: N
authors.initials: N
authors.lastname: Nanayakkara
authors.forename: S C
authors.initials: SC
authors.lastname: Heffelfinger
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001807:Blood Vessel Prosthesis; D004396:Coloring Agents; D003893:Desmin / Q000032:analysis; D016228:Endothelial Growth Factors / Q000032:analysis; D004801:Eosine Yellowish-(YS); D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006083:Graft Occlusion, Vascular / Q000473:pathology*; D006416:Hematoxylin; D006801:Humans; D006965:Hyperplasia; D019394:Ki-67 Antigen / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008222:Lymphokines / Q000032:analysis; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D011138:Polytetrafluoroethylene; D011475:Prosthesis Failure; D006435:Renal Dialysis; D013927:Thrombosis / Q000473:pathology; D017539:Tunica Intima / Q000737:chemistry / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014680:Veins / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000199:Actins; D004396:Coloring Agents; D003893:Desmin; D016228:Endothelial Growth Factors; D019394:Ki-67 Antigen; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor; D016222:Fibroblast Growth Factor 2; D011138:Polytetrafluoroethylene; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin