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Although smoking-related coronary vascular disease is well documented, the effects of nicotine have not been fully investigated. There is controversy over reports about the effect of nicotine on apoptosis. The effect of nicotine on apoptosis of human umbilical vein endothelial cells (HUVECs) and the expressions of Fas/Fas ligand (FasL) and caspase-3 were evaluated in this study. Annexin V fluorescein isothiocyanate and propidium iodide double staining demonstrated that nicotine (0.2 microM, 0.5 microM and 1 microM) could induce apoptosis of HUVECs; reverse transcription (RT)-PCR and Western blotting analysis demonstrated that levels of Fas and FasL expression were increased in nicotine-treated HUVECs. Moreover, caspase-3 expression was also increased. These data indicate that nicotine induces the apoptosis of HUVECs, and that the Fas/FasL pathway may play an important role. This provides evidence that nicotine may have an important role in cardiovascular pathology and atherogenesis.