Nicotine induces tissue factor expression in cultured endothelial and smooth muscle cells.

Background: Cigarette smoking is associated with an increased risk to develop myocardial infarction and ischemic stroke. However, the mechanisms responsible for these effects are still poorly understood. Thus, the aim of the present study was to investigate whether nicotine and cotinine, two major components of cigarette smoking, might induce a pro-thrombotic state via stimulation of tissue factor (TF) expression in endothelial (ECs) and smooth muscle cells (SMCs). Methods and Results: Incubation of ECs and SMCs with nicotine and cotinine induced tissue factor (TF) expression in both cell types in a dose-dependent fashion, exerting its effect at the transcriptional level, as demonstrated by semiquantitative RT-PCR. Nicotine and cotinine-induced TF expression was mediated by activation of the transcription factor, NF-kB, as demonstrated by electrophoretic mobility shift assay and by suppression of TF expression by the NF-kB inhibitor, pyrrolidine dithio carbamate ammonium. Conclusions: These data indicate that nicotine and cotinine exert direct effects on ECs and SMCs, shifting them toward a pro-thrombotic state via induction of TF expression. These effects on cells of the vessel wall might explain, at least in part, the deleterious cardiovascular consequences of cigarette smoking.