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International Journal of Inflammation
Volume 2011, Article ID 936109, 9 pages
http://dx.doi.org/10.4061/2011/936109
Research Article

Atherosclerotic Plaque Stability Is Affected by the Chemokine CXCL10 in Both Mice and Humans

1Department of Cardiology, Erasmus University Medical Center, 3522ZZ Rotterdam, The Netherlands
2Department of Immunology, Erasmus University Medical Center, 3522ZZ Rotterdam, The Netherlands
3Department of Cardiology, University Medical Center-Utrecht, 3584CX Utrecht, The Netherlands
4Department of Vascular Surgery, University Medical Center-Utrecht, 3584CX Utrecht, The Netherlands
5Department of Cell Biology and Genetics, Erasmus University Medical Center, 3522ZZ Rotterdam, The Netherlands
6Department of Bioengineering, Royal School of Mines, Imperial College, London SW7 2AZ, UK

Received 29 June 2011; Accepted 25 August 2011

Academic Editor: Elena Aikawa

Copyright © 2011 Dolf Segers et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. The chemokine CXCL10 is specifically upregulated during experimental development of plaque with an unstable phenotype. In this study we evaluated the functional consequences of these findings in mice and humans. Methods and Results. In mice, we induced unstable plaque with using a flow-altering device around the carotid artery. From week 1 to 4, mice were injected with a neutralizing CXCL10 antibody. After 9 weeks, CXCL10 inhibition resulted in a more stable plaque phenotype: collagen increased by 58% ( ), smooth muscle cell content increased 2-fold ( ), while macrophage MHC class II expression decreased by 50% ( ). Also, the size of necrotic cores decreased by 41% ( ). In 106 human carotid endarterectomy specimens we found that increasing concentrations of CXCL10 strongly associate with an increase in atheromatous plaque phenotype (ANOVA, ), with high macrophage, low smooth muscle cell, and low collagen content. Conclusions. In the present study we showed that CXCL10 is associated with the development of vulnerable plaque in human and mice. We conclude that CXCL10 might provide a new lead towards plaque-stabilizing therapy.