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Coagulation factor XIIIa and activated protein C activate platelets via GPVI and PAR1

De Simone, I., Baaten, C. C. F. M. J., Jandrot-Perrus, M., Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352, ten Cate, H., Heemskerk, J. W. M., Jones, C. I. ORCID: https://orcid.org/0000-0001-7537-1509 and van der Meijden, P. E. J. (2022) Coagulation factor XIIIa and activated protein C activate platelets via GPVI and PAR1. International Journal of Molecular Sciences, 23 (18). 10203. ISSN 1422-0067

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To link to this item DOI: 10.3390/ijms231810203

Abstract/Summary

Platelet and coagulation activation are highly reciprocal processes. Activated platelets secrete several coagulation factors and expose phosphatidylserine, which supports the activation of coagulation factors. On the other hand, the coagulation cascade generates known ligands for platelet receptors, such as thrombin and fibrin. Coagulation factor (F)Xa, (F)XIIIa and activated protein C (APC) can also bind to platelets, but the functional consequences are unclear. Here, we investigated the effects of the activated (anti)coagulation factors on platelets, other than thrombin. Multicolor flow cytometry and aggregation experiments revealed that the ‘supernatant of (hirudin-treated) coagulated plasma’ (SCP) enhanced CRP-XL-induced platelet responses, i.e., integrin αIIbβ3 activation, P-selectin exposure and aggregate formation. We demonstrated that FXIIIa in combination with APC enhanced platelet activation in solution, and separately immobilized FXIIIa and APC resulted in platelet spreading. Platelet activation by FXIIIa was inhibited by blockade of glycoprotein VI (GPVI) or Syk kinase. In contrast, platelet spreading on immobilized APC was inhibited by PAR1 blockade. Immobilized, but not soluble, FXIIIa and APC also enhanced in vitro adhesion and aggregation under flow. In conclusion, in coagulation, factors other than thrombin or fibrin can induce platelet activation via GPVI and PAR receptors.

Item Type:Article
Refereed:Yes
Divisions:Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:107578
Publisher:MDPI

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