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

18 Citations (Scopus)

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

Fingerprint

Nicotine
Growth
Vascular Smooth Muscle
Cell Proliferation
Smooth Muscle Myocytes
Wounds and Injuries
Early Growth Response Protein 1
Neointima
Lentivirus
Mitogen-Activated Protein Kinase 3
Iliac Artery
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
Nicotinic Receptors
Small Interfering RNA
Cultured Cells
Up-Regulation
Arteries
Phosphorylation

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

Novel role of Egr-1 in nicotine-related neointimal formation. / Vazquez-Padron, Roberto I; Mateu, Dania; Rodriguez-Menocal, Luis; Wei, Yuntao; Webster, Keith A; Pham, Si M.

In: Cardiovascular Research, Vol. 88, No. 2, 01.11.2010, p. 296-303.

Research output: Contribution to journalArticle

Vazquez-Padron, RI, Mateu, D, Rodriguez-Menocal, L, Wei, Y, Webster, KA & Pham, SM 2010, 'Novel role of Egr-1 in nicotine-related neointimal formation', Cardiovascular Research, vol. 88, no. 2, pp. 296-303. https://doi.org/10.1093/cvr/cvq213
Vazquez-Padron RI, Mateu D, Rodriguez-Menocal L, Wei Y, Webster KA, Pham SM. Novel role of Egr-1 in nicotine-related neointimal formation. Cardiovascular Research. 2010 Nov 1;88(2):296-303. https://doi.org/10.1093/cvr/cvq213
Vazquez-Padron, Roberto I ; Mateu, Dania ; Rodriguez-Menocal, Luis ; Wei, Yuntao ; Webster, Keith A ; Pham, Si M. / Novel role of Egr-1 in nicotine-related neointimal formation. In: Cardiovascular Research. 2010 ; Vol. 88, No. 2. pp. 296-303.
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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.",
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N2 - 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.

AB - 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.

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