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Disruption of Stromal-Derived Factor-1/Chemokine Receptor 4 by Simvastatin

AUTHORS

M Masori , A Jalili , * , Y Nakaya

AUTHORS INFORMATION

How to Cite: Masori M , Jalili A , Nakaya Y . Disruption of Stromal-Derived Factor-1/Chemokine Receptor 4 by Simvastatin, Int Cardio Res J. 2010 ; 4(1):e67617.

ARTICLE INFORMATION

International Cardiovascular Research Journal: 4 (1); e67617
Published Online: March 31, 2010
Article Type: Research Article
Received: February 16, 2010
Accepted: March 30, 2010

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Abstract

Background: The alpha chemokine, stromal-derived factor (SDF)-1 is produced by bone marrow stromal cells
and other cells, especially damaged tissues. SDF-1 receptor, a chemokine receptor 4 (CXCR4), is expressed
on inflammatory cells and that SDF-1/CXCR4 axis plays a critical role in migration of inflammatory cells. In
cardiovascular diseases, SDF-1 is produced by endothelial cells and plaques and that SDF-1 chemoattracts
monocytes to the endothelial cells resulting in a local inflammation. Simvastatin, a cholesterol-lowering agent,
is a general drug for treatment of cardiovascular diseases. However, its molecular mechanism has not yet been
completely elucidated.
Method: Herein, we investigated the role of simvastatin on the SDF- 1/CXCR4 axis by employing flow cytometry,
RT-PCR, chemotaxis and adhesion assays.
Results: Simvastatin (i) downregulates CXCR4 expression on monocytic cell line (THP-1) and primary monocyte
in a dose-dependent manner, (ii) inhibits adhesion of monocytes to endothelial cells and (iii) decreases
SDF-1 production by endothelial cells. Moreover, preincubation with simvastatin significantly decreased the
migration of THP-1 towards the SDF-1 gradient.
Conclusion: All together our data indicate that simvastatin inhibits the binding of monocytes to endothelial cells
through disrupting of the SDF-1/CXCR4 axis.

Keywords

SDF-1 CXCR4 Monocytes Atherosclerosis Simvastatin

© 0, Shiraz University of Medical Sciences.

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