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The role of platelet P2Y12 receptors in inflammation

Journal

BRITISH JOURNAL OF PHARMACOLOGY
Volume -, Issue -, Pages -

Publisher

WILEY
DOI: 10.1111/bph.16256

Keywords

inflammation; leucocytes; P2Y(12) receptors; platelets

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Inflammation is a complex pathophysiological process where platelets play a crucial role in the thrombo-inflammatory response through activation and aggregation mediated by the P2Y(12) receptors. Studies using receptor antagonists like thienopyridines have shown the significant involvement of P2Y(12) receptors in inflammation, suggesting potential therapeutic strategies for a variety of inflammatory conditions.
Inflammation is a complex pathophysiological process underlying many clinical conditions. Platelets contribute to the thrombo-inflammatory response. Platelet P2Y(12 )receptors amplify platelet activation, potentiating platelet aggregation, degranulation and shape change. The contents of platelet alpha granules, in particular, act directly on leucocytes, including mediating platelet-leucocyte aggregation and activation via platelet P-selectin. Much evidence for the role of platelet P2Y(12) receptors in inflammation comes from studies using antagonists of these receptors, such as the thienopyridines clopidogrel and prasugrel, and the cyclopentyltriazolopyrimidine ticagrelor, in animal and human experimental models. These suggest that antagonism of P2Y(12) receptors decreases markers of inflammation with some evidence that this reduces incidence of adverse clinical sequelae during inflammatory conditions. Interpretation is complicated by pleiotropic effects such as those of the thienopyridines on circulating leucocyte numbers and of ticagrelor on adenosine reuptake. The available evidence suggests that P2Y(12) receptors are prominent mediators of inflammation and P2Y(12) receptor antagonism as a potentially powerful strategy in a broad range of inflammatory conditions.

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