Skip Navigation



ToxSci Advance Access published online on August 20, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn173
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
106/2/546    most recent
kfn173v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Xu, C.-B.
Right arrow Articles by Edvinsson, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, C.-B.
Right arrow Articles by Edvinsson, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Lipid soluble smoke particles up-regulate vascular smooth muscle ETB receptors via activation of mitogen activating protein kinases and NF-kappaB pathways.

Cang-Bao Xu*,{dagger}, Jian-Pu Zheng*, Wei Zhang{dagger}, Yaping Zhang{dagger} and Lars Edvinsson*,{dagger}

* Division of Experimental Vascular Research, Institute of Clinical Science in Lund, Lund University, Lund, Sweden {dagger} Department of Clinical and Experimental Research, Glostrup Hospital, Copenhagen University, Copenhagen, Denmark

Correspondence should be addressed to: Cang-Bao Xu, MD, PhD, Division of Experimental Vascular Research, BMC A13, WNC, Institute of Clinical Science in Lund, Lund University, 221 84 Lund, Sweden, Phone: +46-46-2220825. Fax: +46-46-2220616. Email: Cang-Bao.Xu{at}med.lu.se

Received May 10, 2008; revision received July 20, 2008; accepted August 12, 2008


  Abstract

Cigarette smoke is a strong risk factor for cardiovascular disease. However, the underlying molecular mechanisms that lead to cigarette smoke-associated cardiovascular disease remain elusive. With functional and molecular methods, we demonstrate for the first time that lipid soluble cigarette smoke particles (DSP) increased the expression of endothelin type B (ETB) receptors in arterial smooth muscle cells. The increased ETB receptors in arterial smooth muscle cells was documented as enhanced contractility (sensitive myograph technique), elevated levels of ETB receptor mRNA (quantitative real-time PCR) and protein expressions (immunohistochemistry and Western blotting). Intracellular signalling was studied with Western blotting and phosphoELISA; this revealed that DSP induced extracellular-regulated protein kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappaB (NF-{kappa}B) phosphorylation within 3 hours. Blocking ERK1/2, p38 or NF-{kappa}B activation by their specific inhibitors significantly attenuated the DSP-induced up-regulation of ETB receptor-mediated contraction and both ETB receptor mRNA and protein expression. In addition, dexamethasone abolished the DSP-induced up-regulation of ETB receptor-mediated contraction. In conclusion, up-regulation of ETB receptors by DSP in arterial smooth muscle cells involves activation of mitogen activating protein kinases (ERK1/2 and p38) and the downstream transcriptional factor NF-{kappa}B pathways.

Key Words: smoking; ETB receptor; MAPK; VSMC; vascular disease.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.