Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells in vitro

Research output: Contribution to journalArticle

192 Scopus citations

Abstract

Nicotine is a major component of cigarette smoke and has been postulated to play an important role in atherogenesis and malignancy. Endothelial cell growth may be regulated by nicotine, yet operative mechanisms at the endothelial level are poorly understood. We studied the effects of nicotine (10-14-10-4 M) on endothelial DNA synthesis, DNA repair, proliferation, and cytotoxicity by using cultures of bovine pulmonary artery endothelial cells. Assays were performed on cells incubated with nicotine in the presence and absence of hydroxyurea (an inhibitor of scheduled DNA synthesis), serum, human platelet-poor plasma, and platelet-derived growth factor and endothelial cell growth factor (PDGF and PDECGF, respectively). Nicotine significantly stimulated endothelial cell DNA synthesis and proliferation at concentrations lower than those obtained in blood after smoking (<10-8 M). The stimulatory effects of nicotine were enhanced by serum (0.5%) and PDECGF and were blocked by the nicotinic-receptor antagonist hexamethonium. The response to nicotine was bimodal because cytotoxicity was observed at higher concentrations (>10-6 M). This study has implications for understanding cellular mechanisms of nicotine action. The results may be important in tumor angiogenesis, atherogenesis, and vascular dysfunction in smokers.

Original languageEnglish (US)
Pages (from-to)2089-2098
Number of pages10
JournalJournal of Applied Physiology
Volume84
Issue number6
StatePublished - Jun 1998

    Fingerprint

Keywords

  • Angiogenesis
  • Hexamethonium
  • Hydroxyurea
  • Plasma
  • Platelet-derived growth factors
  • Serum
  • Smoking
  • Tumor

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this