Fractalkine Is Expressed in Early and Advanced Atherosclerotic Lesions and Supports Monocyte Recruitment via CX3CR1

被引:52
作者
Stolla, Moritz [1 ,2 ]
Pelisek, Jaroslav [3 ]
von Bruehl, Marie-Luise [4 ,5 ]
Schaefer, Andreas [6 ]
Barocke, Verena [4 ,5 ]
Heider, Peter [3 ]
Lorenz, Michael [4 ,5 ]
Tirniceriu, Anca [4 ,5 ]
Steinhart, Alexander [4 ,5 ]
Bauersachs, Johann [6 ]
Bray, Paul F. [1 ,2 ]
Massberg, Steffen [4 ,5 ]
Schulz, Christian [4 ,5 ]
机构
[1] Thomas Jefferson Univ, Jefferson Med Coll, Cardeza Fdn, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA
[3] Tech Univ Munich, Klinikum Rechts Isar, Abt Gefasschirurgie, D-8000 Munich, Germany
[4] Tech Univ Munich, Klinikum Rechts Isar, Med Klin, Deutsch Herzzentrum, D-8000 Munich, Germany
[5] Munich Heart Alliance, Munich, Germany
[6] Hannover Med Sch, Klin Kardiol & Angiol, D-30623 Hannover, Germany
来源
PLOS ONE | 2012年 / 7卷 / 08期
关键词
AMERICAN-HEART-ASSOCIATION; CORONARY-ARTERY-DISEASE; IN-VIVO; RECEPTOR CX(3)CR1; PLATELET-ADHESION; VASCULAR-LESIONS; UNSTABLE ANGINA; TISSUE FACTOR; AORTIC-WALL; CHEMOKINE;
D O I
10.1371/journal.pone.0043572
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:9
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