title: N-acetylcysteine prevents neointima formation in experimental venous bypass grafts.
abstract: BACKGROUND
  Neointima formation, mainly characterized by smooth muscle cell proliferation, is an important cause of venous bypass graft failure. The therapeutic potential of the antioxidant N-acetylcysteine (NAC) to attenuate smooth muscle cell proliferation and neointima formation was examined in vivo. The effects of NAC on hyperoxia-induced venous smooth muscle cell (VSMC) cytokine production and proliferation were addressed in vitro.
  
  
  METHODS
  Rats underwent autologous epigastric vein-to-femoral artery interposition grafting. Fourteen rats received oral NAC, and a similar control group received saline. Histomorphometric analysis was performed after 7 days or 3 weeks. Cytokine analysis and cell proliferation assay were performed in cultured human VSMCs after hyperoxic or normoxic exposure and NAC administration.
  
  
  RESULTS
  NAC-treated rats displayed a threefold reduction in neointimal area, a sixfold reduction in stenosis rate, and a twofold reduction in VSMC proliferation after vein graft surgery. Incubation of VSMCs in 70 per cent oxygen stimulated the release of mitogenic inflammatory cytokines interleukin (IL) 6 and IL-8. Cytokine-rich medium from these VSMCs induced proliferation of normoxic VSMCs. NAC inhibited hyperoxia-induced cytokine release and VSMC proliferation.
  
  
  CONCLUSIONS
  NAC attenuated neointima formation and vein graft stenosis by reducing VSMC proliferation in vivo, and prevented hyperoxia-induced cytokine production and VSMC proliferation in vitro.
authors: Department of Surgery, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands.
authors: R
authors: R
authors: de Graaf
authors: A
authors: A
authors: Tintu
authors: F
authors: F
authors: Stassen
authors: G
authors: G
authors: Kloppenburg
authors: C
authors: C
authors: Bruggeman
authors: E
authors: E
authors: Rouwet
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001163:Arteriovenous Anastomosis; D001807:Blood Vessel Prosthesis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005263:Femoral Artery; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D032389:Myocytes, Smooth Muscle; D051381:Rats; D011917:Rats, Inbred Lew; D017539:Tunica Intima / Q000187:drug effects*; D014680:Veins
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D000111:Acetylcysteine