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PMID: 17304353 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Shear stress-induced changes in atherosclerotic plaque composition are modulated by chemokines.

The Journal of clinical investigation ·Vol. 117 ·No. 3 ·2007-03-00 ·Pages 616-26

Cheng C, Tempel D, van Haperen R, de Boer HC, Segers D, Huisman M, van Zonneveld AJ, Leenen PJ, van der Steen A, Serruys PW, de Crom R, Krams R

Abstract

We previously found that low shear stress (LSS) induces atherosclerotic plaques in mice with increased lipid and matrix metalloproteinase content and decreased vascular smooth muscle and collagen content. Here, we evaluated the role of chemokines in this process, using an extravascular device inducing regions of LSS, high shear stress, and oscillatory shear stress (OSS) in the carotid artery. One week of shear stress alterations induced expression of IFN-gamma-inducible protein-10 (IP-10) exclusively in the LSS region, whereas monocyte chemoattractant protein-1 (MCP-1) and the mouse homolog of growth-regulated oncogene alpha (GRO-alpha) were equally upregulated in both LSS and OSS regions. After 3 weeks, GRO-alpha and IP-10 were specifically upregulated in LSS regions. After 9 weeks, lesions with thinner fibrous caps and larger necrotic cores were found in the LSS region compared with the OSS region. Equal levels of MCP-1 expression were observed in both regions, while expression of fractalkine was found in the LSS region only. Blockage of fractalkine inhibited plaque growth and resulted in striking differences in plaque composition in the LSS region. We conclude that LSS or OSS triggers expression of chemokines involved in atherogenesis. Fractalkine upregulation is critically important for the composition of LSS-induced atherosclerotic lesions.

MeSH Terms
Animals Apolipoproteins E/genetics Atherosclerosis/etiology,pathology CX3C Chemokine Receptor 1 Carotid Arteries/chemistry,pathology Carotid Artery Diseases/etiology,pathology Chemokines/genetics,physiology Gene Expression Mice Mice, Mutant Strains Receptors, Cytokine/analysis Receptors, HIV/analysis Shear Strength Stress, Mechanical
Chemicals
Apolipoproteins E CX3C Chemokine Receptor 1 Chemokines Receptors, Cytokine Receptors, HIV
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Cheng Caroline
Department of Cardiology, Thoraxcenter, Rotterdam, The Netherlands.
Tempel Dennie
van Haperen Rien
de Boer Hetty C
Segers Dolf
Huisman Martin
van Zonneveld Anton Jan
Leenen Pieter J M
van der Steen Anton
Serruys Patrick W
de Crom Rini
Krams Rob
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
2007-03-00
Epub
2007-00-15
Pages
616-26
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1794116
Subset
IM
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