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Cigarette smoke modulates vascular smooth muscle phenotype: implications for carotid and cerebrovascular disease.

Publication ,  Journal Article
Starke, RM; Ali, MS; Jabbour, PM; Tjoumakaris, SI; Gonzalez, F; Hasan, DM; Rosenwasser, RH; Owens, GK; Koch, WJ; Dumont, AS
Published in: PLoS One
2013

BACKGROUND: The role of smooth muscle cell (SMC) phenotypic modulation in the cerebral circulation and pathogenesis of stroke has not been determined. Cigarette smoke is a major risk factor for atherosclerosis, but potential mechanisms are unclear, and its role in SMC phenotypic modulation has not been established. METHODS AND RESULTS: In cultured cerebral vascular SMCs, exposure to cigarette smoke extract (CSE) resulted in decreased promoter activity and mRNA expression of key SMC contractile genes (SM-α-actin, SM-22α, SM-MHC) and the transcription factor myocardin in a dose-dependent manner. CSE also induced pro-inflammatory/matrix remodeling genes (MCP-1, MMPs, TNF-α, IL-1β, NF-κB). CSE increased expression of KLF4, a known regulator of SMC differentiation, and siKLF4 inhibited CSE induced suppression of SMC contractile genes and myocardin and activation of inflammatory genes. These mechanisms were confirmed in vivo following exposure of rat carotid arteries to CSE. Chromatin immune-precipitation assays in vivo and in vitro demonstrated that CSE promotes epigenetic changes with binding of KLF4 to the promoter regions of myocardin and SMC marker genes and alterations in promoter acetylation and methylation. CONCLUSION: CSE exposure results in phenotypic modulation of cerebral SMC through myocardin and KLF4 dependent mechanisms. These results provides a mechanism by which cigarette smoke induces a pro-inflammatory/matrix remodeling phenotype in SMC and an important pathway for cigarette smoke to contribute to atherosclerosis and stroke.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

8

Start / End Page

e71954

Location

United States

Related Subject Headings

  • Trans-Activators
  • Tobacco Products
  • Smoke
  • Rats, Sprague-Dawley
  • Rats
  • Promoter Regions, Genetic
  • Phenotype
  • Nuclear Proteins
  • Muscle, Smooth, Vascular
  • Kruppel-Like Transcription Factors
 

Citation

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Starke, R. M., Ali, M. S., Jabbour, P. M., Tjoumakaris, S. I., Gonzalez, F., Hasan, D. M., … Dumont, A. S. (2013). Cigarette smoke modulates vascular smooth muscle phenotype: implications for carotid and cerebrovascular disease. PLoS One, 8(8), e71954. https://doi.org/10.1371/journal.pone.0071954
Starke, Robert M., Muhammad S. Ali, Pascal M. Jabbour, Stavropoula I. Tjoumakaris, Fernando Gonzalez, David M. Hasan, Robert H. Rosenwasser, Gary K. Owens, Walter J. Koch, and Aaron S. Dumont. “Cigarette smoke modulates vascular smooth muscle phenotype: implications for carotid and cerebrovascular disease.PLoS One 8, no. 8 (2013): e71954. https://doi.org/10.1371/journal.pone.0071954.
Starke RM, Ali MS, Jabbour PM, Tjoumakaris SI, Gonzalez F, Hasan DM, et al. Cigarette smoke modulates vascular smooth muscle phenotype: implications for carotid and cerebrovascular disease. PLoS One. 2013;8(8):e71954.
Starke, Robert M., et al. “Cigarette smoke modulates vascular smooth muscle phenotype: implications for carotid and cerebrovascular disease.PLoS One, vol. 8, no. 8, 2013, p. e71954. Pubmed, doi:10.1371/journal.pone.0071954.
Starke RM, Ali MS, Jabbour PM, Tjoumakaris SI, Gonzalez F, Hasan DM, Rosenwasser RH, Owens GK, Koch WJ, Dumont AS. Cigarette smoke modulates vascular smooth muscle phenotype: implications for carotid and cerebrovascular disease. PLoS One. 2013;8(8):e71954.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

8

Start / End Page

e71954

Location

United States

Related Subject Headings

  • Trans-Activators
  • Tobacco Products
  • Smoke
  • Rats, Sprague-Dawley
  • Rats
  • Promoter Regions, Genetic
  • Phenotype
  • Nuclear Proteins
  • Muscle, Smooth, Vascular
  • Kruppel-Like Transcription Factors