Novel role of Egr-1 in nicotine-related neointimal formation

Roberto I. Vazquez-Padron, Dania Mateu, Luis Rodriguez-Menocal, Yuntao Wei, Keith A. Webster, Si M. Pham

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Aims The aim of this study was to investigate the mechanisms by which nicotine increases vascular smooth muscle cell (VSMC) proliferation and post-injury neointimal formation. Methods and resultsVascular injury was inflicted in the right iliac artery of nicotine-treated and control rats. Nicotine increased post-injury VSMC proliferation (Ki67+ cells) and neointimal formation (neointima/media ratio, 0.42 ± 0.23 vs. 0.14 ± 0.07, P= 0.02). To determine the mechanisms by which nicotine exacerbates VSMC proliferation, cultured cells were exposed to nicotine, and signalling pathways leading to cell proliferation were studied. Nicotine activated extracellular signal-regulated kinase (ERK) 1/2 in a dose-and time-dependent manner. The blockade of this signalling axis abolished nicotine-mediated proliferation. Functional nicotinic acetylcholine receptors and Ca2+ influx were necessary for ERK1/2 activation and nicotine-induced mitogenesis in VSMCs. Downstream to ERK1/2, nicotine induced the phosphorylation of Ets-like gene 1 in a timely co-ordinated manner with the up-regulation of the atherogenic transcription factor, early growth response 1 (Egr-1). The treatment of balloon-injured arteries with a lentivirus vector carrying a short hairpin RNA against Egr-1 abolished the deleterious effect of nicotine on vascular remodelling.Conclusion Nicotine acts through its receptors in VSMC to activate the ERK-Egr-1 signaling cascade that induces cell proliferation and exacerbates post-injury neointimal development.

Original languageEnglish (US)
Pages (from-to)296-303
Number of pages8
JournalCardiovascular Research
Volume88
Issue number2
DOIs
StatePublished - Nov 1 2010

Keywords

  • Egr-1
  • Extracellular signal-regulated kinase
  • Neointima
  • Nicotine
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

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    Vazquez-Padron, R. I., Mateu, D., Rodriguez-Menocal, L., Wei, Y., Webster, K. A., & Pham, S. M. (2010). Novel role of Egr-1 in nicotine-related neointimal formation. Cardiovascular Research, 88(2), 296-303. https://doi.org/10.1093/cvr/cvq213