Platelet GPVI (Glycoprotein VI) and Thrombotic Complications in the Venous System

G. Perrella*, M. Nagy, S.P. Watson, J.W.M. Heemskerk

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

8 Citations (Web of Science)

Abstract

The immunoglobulin receptor GPVI (glycoprotein VI) is selectively expressed on megakaryocytes and platelets and is currently recognized as a receptor for not only collagen but also a variety of plasma and vascular proteins, including fibrin, fibrinogen, laminin, fibronectin, and galectin-3. Deficiency of GPVI is protective in mouse models of experimental thrombosis, pulmonary thromboembolism as well as in thromboinflammation, suggesting a role of GPVI in arterial and venous thrombus formation. In humans, platelet GPVI deficiency is associated with a mild bleeding phenotype, whereas a common variant rs1613662 in the GP6 gene is considered a risk factor for venous thromboembolism. However, preclinical studies on the inhibition of GPVI-ligand interactions are focused on arterial thrombotic complications. In this review we discuss the emerging evidence for GPVI in venous thrombus formation and leukocyte-dependent thromboinflammation, extending to venous thromboembolism, pulmonary thromboembolism, and cancer metastasis. We also recapitulate indications for circulating soluble GPVI as a biomarker of thrombosis-related complications. Collectively, we conclude that the current evidence suggests that platelet GPVI is also a suitable cotarget in the prevention of venous thrombosis due to its role in thrombus consolidation and platelet-leukocyte complex formation.
Original languageEnglish
Pages (from-to)2681-2692
Number of pages12
JournalArteriosclerosis Thrombosis and Vascular Biology
Volume41
Issue number11
DOIs
Publication statusPublished - 1 Nov 2021

Keywords

  • embolism
  • glycoprotein
  • inflammation
  • thrombosis
  • venous thromboembolism
  • VON-WILLEBRAND-FACTOR
  • DEEP-VEIN THROMBOSIS
  • ANTITHROMBOTIC PROTECTION
  • GRANULE SECRETION
  • DOWN-REGULATION
  • SOLUBLE GPVI
  • IN-VIVO
  • IX-V
  • COLLAGEN
  • ACTIVATION

Cite this