Contribution of Platelet CX(3)CR1 to Platelet-Monocyte Complex Formation and Vascular Recruitment During Hyperlipidemia

Otilia Postea, Elena M. Vasina, Sandra Cauwenberghs, Delia Projahn, Elisa A. Liehn, Dirk Lievens, Wendy Theelen, Birgit K. Kramp, Elena D. Butoi, Oliver Soehnlein, Johan W. M. Heemskerk, Andreas Ludwig, Christian Weber, Rory R. Koenen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

67 Citations (Web of Science)

Abstract

Objective-The chemokine receptor CX(3)CR1 is an inflammatory mediator in vascular diseases. On platelets, its ligation with fractalkine (CX(3)CL1) induces platelet activation followed by leukocyte recruitment to activated endothelium. Here, we evaluated the expression and role of platelet-CX(3)CR1 during hyperlipidemia and vascular injury. Methods and Results-The existence of CX(3)CR1 on platelets at mRNA and protein level was analyzed by RT-PCR, quantitative (q)PCR, FACS analysis, and Western blot. Elevated CX(3)CR1 expression was detected on human platelets after activation and, along with increased binding of CX(3)CL1, platelet CX(3)CR1 was also involved in the formation of platelet-monocyte complexes. Interestingly, the expression of CX(3)CR1 was elevated on platelets from hyperlipidemic mice. Accordingly, CX(3)CL1-binding and the number of circulating platelet-monocyte complexes were increased. In addition, CX(3)CR1 supported monocyte arrest on inflamed smooth muscle cells in vitro, whereas CX(3)CR1-deficient platelets showed decreased adhesion to the denuded vessel wall in vivo. Conclusion-Platelets in hyperlipidemic mice display increased CX(3)CR1-expression and assemble with circulating monocytes. The formation of platelet-monocyte complexes and the detection of platelet-bound CX(3)CL1 on inflamed smooth muscle cells suggest a significant involvement of the CX(3)CL1-CX(3)CR1 axis in platelet accumulation and monocyte recruitment at sites of arterial injury in atherosclerosis. (Arterioscler Thromb Vasc Biol. 2012; 32: 1186-1193.)
Original languageEnglish
Pages (from-to)1186-+
JournalArteriosclerosis Thrombosis and Vascular Biology
Volume32
Issue number5
DOIs
Publication statusPublished - May 2012

Keywords

  • atherosclerosis
  • platelets
  • vascular biology
  • chemokines

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