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

• Published in: Thrombosis and haemostasis Vol. 118; no. 1; p. 195
• Main Authors: Merckelbach, Sophie, van der Vorst, Emiel P C, Kallmayer, Michael, Rischpler, Christoph, Burgkart, Rainer, Döring, Yvonne, de Borst, Gert-Jan, Schwaiger, Markus, Eckstein, Hans-Henning, Weber, Christian, Pelisek, Jaroslav
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2018
• Subjects: Aged; Atherosclerosis; Carotid Arteries - metabolism; Chemokine CCL2 - metabolism; Chemokine CXCL12 - metabolism; Disease Progression; Endarterectomy, Carotid; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunohistochemistry; Macrophage Colony-Stimulating Factor - metabolism; Male; Middle Aged; Plaque, Atherosclerotic - metabolism; Receptors, CCR2 - metabolism; Receptors, CXCR - metabolism; Receptors, CXCR4 - metabolism; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; RNA, Messenger - metabolism
• ISSN: 2567-689X
• DOI: 10.1160/th17-04-0271

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