Fractalkine Activates a Signal Transduction Pathway Similar to P2Y ₁₂ and Is Associated With Impaired Clopidogrel Responsiveness

Depression and Cardiovascular Disease: The Viewpoint of Platelets

“…In addition, fractalkine, through the activation of CX 3 CR1, promotes adhesion of platelets on fibrinogen and collagen [ 326 ], and induces not only monocyte recruitment but also platelet accumulation at sites of arterial injury [ 327 ]. It has been recently demonstrated that also GPIb can acts as a fractalkine receptor [ 328 ], thus suggesting another possible target in regulating platelets activation.…”

“…It has been recently demonstrated that also GPIb can acts as a fractalkine receptor [ 328 ], thus suggesting another possible target in regulating platelets activation. Interestingly, a positive correlation between levels of fractalkine and platelet activation in patients with CVD was identified [ 326 ] ( Table 2 ).…”

Modulation of platelet and monocyte function by the chemokine fractalkine (CX3CL1) in cardiovascular disease

“…Hence, the activation of a similar pathway following platelet fractalkine stimulation was suggested. This observation was proposed to be important in the setting of antiplatelet therapy with P2Y 12 receptor inhibitors as fractalkine‐mediated signalling via CX 3 CR1 might possibly bypass therapeutic P2Y 12 receptor inhibition sustaining platelet activation . Indeed, elevated plasma fractalkine levels are associated with higher platelet reactivity during treatment with clopidogrel in CAD and heart failure .…”

“…This observation was proposed to be important in the setting of antiplatelet therapy with P2Y 12 receptor inhibitors as fractalkine‐mediated signalling via CX 3 CR1 might possibly bypass therapeutic P2Y 12 receptor inhibition sustaining platelet activation . Indeed, elevated plasma fractalkine levels are associated with higher platelet reactivity during treatment with clopidogrel in CAD and heart failure . Interestingly, although CX 3 CR1 had been described as the only destine receptor for fractalkine, there is growing evidence of other binding partners for CX 3 CL1.…”

Discordance Between VASP Phosphorylation and Platelet Aggregation in Defining High On-Clopidogrel Platelet Reactivity After ST-Segment Elevation Myocardial Infarction

“…[11][12][13] Clopidogrel can irreversibly bind to the P2Y 12 receptor, leading to the inhibition of its downstream signaling pathway and consequently contributes to vasodilator-stimulated phosphoprotein phosphorylation (VASP-P)-mediated platelet glycoprotein IIb/IIIa (GPIIb/IIIa) inhibition 14 The platelet VASP-P level can be measured by quantitative flow cytometry (FCM), which is recognized as the most specific method for evaluating the degree of P2Y 12 inhibition and lack of interference with aspirin or GPIIb/IIIa antagonists. 15,16 In addition to platelet VASP-P assay, platelet reactivity could be evaluated by the traditional light transmission aggregometry (LTA). From published literatures, the correlation between these 2 methods is modest, ranging from *0.4 to *0.5, 8,17 which indicates that these 2 methods are not interchangeable.…”