Fractalkine is expressed in early and advanced atherosclerotic lesions and supports monocyte recruitment via CX3CR1.
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.
Cardeza Foundation and the Department of Medicine, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
Moritz
M
Stolla
Jaroslav
J
Pelisek
Marie-Luise
ML
von Brühl
Andreas
A
Schäfer
Verena
V
Barocke
Peter
P
Heider
Michael
M
Lorenz
Anca
A
Tirniceriu
Alexander
A
Steinhart
Johann
J
Bauersachs
Paul F
PF
Bray
Steffen
S
Massberg
Christian
C
Schulz
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*
D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine