Skip Navigation

Cardiovascular Research 2003 58(1):186-195; doi:10.1016/S0008-6363(02)00855-6
© 2003 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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
Google Scholar
Right arrow Articles by Hattori, Y.
Right arrow Articles by Kasai, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hattori, Y.
Right arrow Articles by Kasai, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2003, European Society of Cardiology

Vascular smooth muscle cell activation by C-reactive protein

Yoshiyuki Hattori*, Michiko Matsumura and Kikuo Kasai

Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan

* Corresponding author. Tel.: +81-282-87-2150; fax: +81-282-86-4632. yhattori{at}dokkyomed.ac.jp

Objective: C-reactive protein (CRP) is an important cardiovascular risk factor. Although the role of CRP has been implicated in atherogenesis, its direct effects on vascular cells are poorly defined. Methods: We investigated the responses to CRP in vascular smooth muscle cells (VSMC). Results: The present study shows that CRP induces parallel activation of the redox-responsive transcription factors NF-kappa B (NF-{kappa}B) and AP-1 and increases the activity of the MAP kinases (MAPKs), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38MAPK, in VSMC. C-reactive protein increased the expression of early response genes, c-fos and c-jun and inflammatory genes, monocyte chemoattractant peptide (MCP-1) and interleukin-6 (IL-6). When VSMC were incubated with CRP, the inducible nitric oxide synthase (iNOS) promoter was activated. CRP alone was a weak inducer of NO production in VSMC as measured by determining nitrite levels, and interferon-{gamma} alone was totally ineffective, whereas CRP plus interferon-{gamma} was a powerful stimulus. This synergy for NO production corresponded to the results of iNOS mRNA expression analyzed by Northern blotting. The NF-{kappa}B activation caused by CRP was inhibited by 15-deoxy-12,14-prostaglandin J2 and the PPAR{gamma} activators, rosiglitazone and pioglitazone. Fluvastatin and cerivastatin also reduced the activation of NF-{kappa}B by CRP. Conclusions: CRP causes NF-{kappa}B activation which could lead to the induction of MCP-1, IL-6, and iNOS gene expression. CRP also activates the MAPK->c-Fos/cJun->AP-1 pathway. Thus, CRP may play a role in atherogenesis by activating VSMC.

KEYWORDS Gene expression; Infection/inflammation; Nitric oxide; Signal transduction; Smooth muscle


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


This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
F. Maingrette, L. Li, and G. Renier
C-reactive protein enhances macrophage lipoprotein lipase expression
J. Lipid Res., September 1, 2008; 49(9): 1926 - 1935.
[Abstract] [Full Text] [PDF]

Home page
 Innate ImmunityHome page
H. Loppnow, K. Werdan, and M. Buerke
Invited review: Vascular cells contribute to atherosclerosis by cytokine- and innate-immunity-related inflammatory mechanisms
Innate Immunity, April 1, 2008; 14(2): 63 - 87.
[Abstract] [PDF]


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.