Skip Navigation


Cardiovascular Research Advance Access originally published online on January 10, 2008
Cardiovascular Research 2008 78(1):175-184; doi:10.1093/cvr/cvn007
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
78/1/175    most recent
cvn007v2
cvn007v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
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 ISI Web of Science
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 Tuomisto, T. T.
Right arrow Articles by Ylä-Herttuala, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tuomisto, T. T.
Right arrow Articles by Ylä-Herttuala, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2

Tiina T. Tuomisto1,{dagger}, Henri Lumivuori1,{dagger}, Emilia Kansanen1, Sanna-Kaisa Häkkinen1, Mikko P. Turunen1, Johannes V. van Thienen2, Anton J. Horrevoets2,{ddagger}, Anna-Liisa Levonen1 and Seppo Ylä-Herttuala1,3,4,*

1 Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland
2 Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
3 Department of Medicine, University of Kuopio, Kuopio, Finland
4 Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland

* Corresponding author. Tel: +358 17 162075; fax: +358 17 163751. E-mail address: seppo.ylaherttuala{at}uku.fi

Aims: Statins have beneficial vascular effects beyond their cholesterol-lowering action. Since macrophages play a central role in atherogenesis, we characterized the effects of simvastatin on gene expression profile of human peripheral blood monocyte (HPBM)-macrophages.

Methods and results: Gene expression profile was studied using Affymetrix gene chip analysis. Lentiviral gene transfer of Kruppel-like factor 2 (KLF-2) was used to further study its role in macrophages. Simvastatin treatment lead to downregulation of many pro-inflammatory genes including several chemokines [e.g. monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory proteins-1{alpha} and β, interleukin-2 receptor-β], members of the tumour necrosis factor family (e.g. lymphotoxin β), vascular cell adhesion molecule-1, and tissue factor (TF). Simvastatin also modulated the expression of several transcription factors essential for inflammation: NF-{kappa}B relA/p65 subunit and ets-1 were downregulated, and an atheroprotective transcription factor KLF-2 was upregulated. The effects of simvastatin on MCP-1 and TF could be mimicked by KLF-2 overexpression using lentiviral gene transfer.

Conclusion: Simvastatin has a strong anti-inflammatory effect on HPBM cells including upregulation of the atheroprotective factor KLF-2. This may partly explain the beneficial effects of statins on cardiovascular diseases.

KEYWORDS Atherosclerosis; Gene array analysis; Inflammation; Macrophages; Statins

Time for primary review: 27 days

{dagger}These authors contributed equally to this work.

{ddagger}Present address: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.


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
 Circ. Res.Home page
J. W. Homeister and C. Patterson
Zinc Fingers in the Pizza Pie Aorta
Circ. Res., September 26, 2008; 103(7): 687 - 689.
[Full Text] [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.