Title

Fractalkine is expressed in early and advanced atherosclerotic lesions and supports monocyte recruitment via CX3CR1.

Authors

Moritz Stolla, Cardeza Foundation and the Department of Medicine, Thomas Jefferson University, Jefferson Medical College
Jaroslav Pelisek, Abteilung für Gefäßchirurgie, Klinikum Rechts der Isar, Technische Universität München
Marie-Luise von Brühl, Deutsches Herzzentrum Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München; Munich Heart Alliance, Munich, Germany
Andreas Schäfer, Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover
Verena Barocke, Deutsches Herzzentrum Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München; Munich Heart Alliance, Munich, Germany
Peter Heider, Abteilung für Gefäßchirurgie, Klinikum Rechts der Isar, Technische Universität München
Michael Lorenz, Deutsches Herzzentrum Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München; Munich Heart Alliance, Munich, Germany
Anca Tirniceriu, Deutsches Herzzentrum Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München; Munich Heart Alliance, Munich, Germany
Alexander Steinhart, Deutsches Herzzentrum Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München; Munich Heart Alliance, Munich, Germany
Johann Bauersachs, Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover
Paul F Bray, Cardeza Foundation and the Department of Medicine, Thomas Jefferson University, Jefferson Medical CollegeFollow
Steffen Massberg, Deutsches Herzzentrum Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München; Munich Heart Alliance, Munich, Germany
Christian Schulz, Deutsches Herzzentrum Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München; Munich Heart Alliance, Munich, Germany; Centre for Molecular and Cellular Biology of Inflammation, King's College London, Great Maze Pond

Document Type

Article

Publication Date

8-20-2012

Comments

This article has been peer reviewed. It was published in: PloS One.

Volume 7, Issue 8, 20 August 2012, Article number e43572.

The published version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423360/. DOI: 10.1371/journal.pone.0043572.

Copyright © 2012 Stolla et al.

Abstract

Fractalkine (CX3CL1, FKN) is expressed in the inflamed vascular wall and absence of FKN reduces atherogenesis. Whether FKN is expressed throughout all stages of atherosclerotic disease and whether it directly contributes to monocyte recruitment to atherosclerotic lesions is not known. We collected human atherosclerotic plaque material and blood samples from patients with carotid artery disease undergoing endarterectomy. Plaques were analyzed by immunohistochemistry and qPCR. We found that FKN is expressed at all stages of atherosclerotic lesion formation, and that the number of FKN-expressing cells positively correlates with the number of CX3CR1-positive cells in human carotid artery plaques. In the circulation, soluble FKN levels are significantly elevated in the presence of high-grade (sub-occlusive) stenosis. To determine the role of the FKN-CX3CR1 axis for monocyte adhesion in vivo we then performed intravital videofluorescence microscopy of the carotid artery in ApoE(-/-) mice. Notably, FKN-CX3CR1 interactions are critical for recruitment of circulating monocytes to the injured atherosclerotic vascular wall. Thus, this chemokine dyad could represent an attractive target for anti-atherosclerotic strategies.