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Thromb Haemost 2023; 123(03): 295-306
DOI: 10.1055/a-1983-0457
Cellular Haemostasis and Platelets

Role of GPR56 in Platelet Activation and Arterial Thrombosis

Dongsheng Liu   *
1   Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Peng Zhang   *
1   Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Kandi Zhang
1   Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Changlong Bi
1   Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Li Li
2   Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
,
Yanyan Xu
3   Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Tiantian Zhang
1   Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Junfeng Zhang
1   Department of Cardiology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
› Institutsangaben Funding This work was supported by National Natural Science Foundation of China (No.81670316 and No.81970289 to Dr. J. Zhang) and the SHIPM-mu fund from Shanghai Institute of Precision Medicine, Ninth People's Hospital Shanghai Jiao Tong University School of Medicine (No. JC202005 to Dr. T. Zhang).
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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.




Publikationsverlauf

Eingereicht: 03. Januar 2022

Angenommen: 04. November 2022

Accepted Manuscript online:
19. November 2022

Artikel online veröffentlicht:
02. März 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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