N-acetylcysteine prevents neointima formation in experimental venous bypass grafts

作者：de Graaf R; Tintu A; Stassen F; Kloppenburg G; Bruggeman C; Rouwet E^*

来源：British Journal of Surgery, 2009, 96(8): 941-950.

DOI：10.1002/bjs.6659

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 h 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 me(lium from these VSMCs induced proliferation of normoxic VSMCs. NAC inhibited hyperoxia-induced cytokine release and VSMC proliferation.
Conclusion: 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.

• 出版日期2009-8