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

J Thromb Haemost. 2006 Feb;4(2):453-8. doi: 10.1111/j.1538-7836.2006.01741.x.

Abstract

Background and objectives: 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.

Aim: To investigate whether nicotine, the major component of cigarette smoking, and its main metabolite, cotinine, might induce a pro-thrombotic state via stimulation of tissue factor (TF) expression in two cell population widely represented in the arterial wall such as endothelial cells (ECs), and smooth muscle cells (SMCs).

Methods and results: Incubation of ECs and SMCs with nicotine and cotinine induced TF expression in both cell types in a dose-dependent fashion, exerting its effect at the transcriptional level, as demonstrated by semiquantitative and by real-time PCR. Nicotine- and cotinine-induced TF expression was mediated by the activation of the transcription factor, nuclear factor-kappa B (NF-kappaB), as demonstrated by electrophoretic mobility shift assay and by the suppression of TF expression by the NF-kappaB 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.

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • Cotinine / pharmacology
  • DNA, Complementary / genetics
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism*
  • Gene Expression / drug effects
  • Humans
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism*
  • Myocardial Infarction / etiology
  • NF-kappa B / metabolism
  • Nicotine / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Risk Factors
  • Smoking / adverse effects
  • Stroke / etiology
  • Thromboplastin / genetics*
  • Thrombosis / etiology
  • Transcription, Genetic / drug effects

Substances

  • DNA, Complementary
  • NF-kappa B
  • RNA, Messenger
  • Nicotine
  • Thromboplastin
  • Cotinine