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. 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.

acetylcysteine, animal experiment, animal model, animal tissue, artery intima proliferation, article, cell proliferation, controlled study, cytokine production, cytokine release, femoral artery, graft failure, human, human cell, hyperoxia, interleukin 6, interleukin 8, nonhuman, priority journal, rat, smooth muscle, vein bypass, vein graft,
British Journal of Surgery
Erasmus MC: University Medical Center Rotterdam

de Graaf, R, Tintu, A, Stassen, F, Kloppenburg, G, Bruggeman, C.A, & Rouwet, E.V. (2009). N-acetylcysteine prevents neointima formation in experimental venous bypass grafts. British Journal of Surgery, 96(8), 941–950. doi:10.1002/bjs.6659