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.