Thromb Haemost 2018; 118(01): 195-206
DOI: 10.1160/TH17-04-0271
Atherosclerosis and Ischaemic Disease
Schattauer GmbH Stuttgart

Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques

Sophie Merckelbach
,
Emiel P. C. van der Vorst
,
Michael Kallmayer
,
Christoph Rischpler
,
Rainer Burgkart
,
Yvonne Döring
,
Gert-Jan de Borst
,
Markus Schwaiger
,
Hans-Henning Eckstein
,
Christian Weber
,
Jaroslav Pelisek
Further Information

Publication History

24 April 2017

19 September 2017

Publication Date:
05 January 2018 (online)

Abstract

Background and Aims The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclerotic plaques.

Methods Carotid plaques (n = 58; 31 stable, 27 unstable, based on histological characterization of plaque morphology) were obtained during carotid endarterectomy, and 10 healthy vessels were used as a control. Expression of cxcr4, cxcr7, cxcl12, ccl2/ccr2 and csf1/csf1r was analysed at mRNA, and level expression of CXCR4, CXCR7 and CXCL12 was analysed at protein level. Cellular localization was determined using consecutive and double immunohistochemical (IHC) staining and microdissection.

Results At mRNA level, cxcr4, cxcr7 and cxcl12 were significantly higher expressed in stable carotid plaques compared with controls (p = 0.011, p < 0.001 and p < 0.001). Cxcl12 mRNA expression was successively augmented toward unstable plaques (p < 0.001). At protein level, CXCR4, CXCR7 and CXCL12 expression was significantly increased in both stable (p = 0.001, p < 0.001 and p = 0.035, respectively) and unstable (p = 0.003, p < 0.001 and p = 0.045, respectively) plaques compared with controls. Using IHC, CXCR4 was particularly localized in macrophages and small neovessels. Microdissection confirmed strongest expression of cxcr4 in macrophages within atherosclerotic plaques. Leukocytes and smooth muscle cells showed cxcr4 expression as well. For cxcl12, only microdissected areas with macrophages were positive.

Conclusion Expression of CXCR4 and CXCL12 was significantly increased in both stable and unstable carotid atherosclerotic plaques compared with healthy vessels, both at mRNA and protein level. CXCR4 and CXCL12 were localized particularly in macrophages.

The review process for this paper was fully handled by Gregory Y. H. Lip, Editor in Chief.


Supplementary Material

 
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