Role of GPR56 in Platelet Activation and Arterial Thrombosis

Abstract

The adhesion G protein-coupled receptor GPR56 mediates cell–cell and cell–extracellular matrix interactions. To examine the function of GPR56 in platelet activation and arterial thrombosis, we generated GPR56-knockout mice and evaluated GPR56 expression in human and mouse platelets. The results revealed that the levels of the GPR56 N-terminal fragment were significantly higher on the first day after myocardial infarction than on the seventh day in the plasma of patients with ST-segment-elevation myocardial infarction. Next, we investigated the effects of GPR56 on platelet function in vitro and in vivo. We observed that collagen-induced aggregation and adenosine triphosphate release were reduced in Gpr56 ^−/− platelets. Furthermore, P-selectin expression on the Gpr56 ^−/− platelet surface was also reduced, and the spreading area on immobilized collagen was decreased in Gpr56 ^−/− platelets. Furthermore, collagen-induced platelet activation in human platelets was inhibited by an anti-GPR56 antibody. Gpr56 ^−/− mice showed an extended time to the first occlusion in models with cremaster arteriole laser injury and FeCl₃-induced carotid artery injury. GPR56 activated the G protein 13 signaling pathway following collagen stimulation, which promoted platelet adhesion and thrombus formation at the site of vascular injury. Thus, our study confirmed that GPR56 regulated the formation of arterial thrombosis. Inhibition of the initial response of GPR56 to collagen could significantly inhibit platelet activation and thrombus formation. Our results provide new insights for research into antiplatelet drugs.

Keywords

GPR56 - collagen - STEMI - platelet activation - arterial thrombosis - G13-GTP pathway - antiplatelet drugs

Author Contributions

D.L., P.Z., J.Z., Y.X., and T.Z. designed the experiments, analyzed data, and wrote the paper. K.Z. and C.B. performed the experiments. L.L. helped with the experiments.

^* First authors.

Publication History

Received: 03 January 2022

Accepted: 04 November 2022

Accepted Manuscript online:
19 November 2022

Article published online:
02 March 2023

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