Contribution of Platelet CX3CR1 to Platelet-Monocyte Complex Formation and Vascular Recruitment During Hyperlipidemia
Objective—The chemokine receptor CX3CR1 is an inflammatory mediator in vascular diseases. On platelets, its ligation with fractalkine (CX3CL1) induces platelet activation followed by leukocyte recruitment to activated endothelium. Here, we evaluated the expression and role of platelet-CX3CR1 during hyperlipidemia and vascular injury.
Methods and Results—The existence of CX3CR1 on platelets at mRNA and protein level was analyzed by RT-PCR, quantitative (q)PCR, FACS analysis, and Western blot. Elevated CX3CR1 expression was detected on human platelets after activation and, along with increased binding of CX3CL1, platelet CX3CR1 was also involved in the formation of platelet-monocyte complexes. Interestingly, the expression of CX3CR1 was elevated on platelets from hyperlipidemic mice. Accordingly, CX3CL1-binding and the number of circulating platelet-monocyte complexes were increased. In addition, CX3CR1 supported monocyte arrest on inflamed smooth muscle cells in vitro, whereas CX3CR1-deficient platelets showed decreased adhesion to the denuded vessel wall in vivo.
Conclusion—Platelets in hyperlipidemic mice display increased CX3CR1-expression and assemble with circulating monocytes. The formation of platelet-monocyte complexes and the detection of platelet-bound CX3CL1 on inflamed smooth muscle cells suggest a significant involvement of the CX3CR1–CX3CL1 axis in platelet accumulation and monocyte recruitment at sites of arterial injury in atherosclerosis.
- Received July 26, 2010.
- Accepted February 21, 2012.
- © 2012 American Heart Association, Inc.