Platelet GPVI (glycoprotein VI) and thrombotic complications in the venous system

Gina Perrella, Magdolna Nagy, Steve Watson, Johan W M Heemskerk

Research output: Contribution to journalReview articlepeer-review

35 Downloads (Pure)

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
JournalArteriosclerosis Thrombosis and Vascular Biology
Volume41
Issue number11
DOIs
Publication statusPublished - 9 Sep 2021

Keywords

  • venous thromboembolism
  • embolism
  • inflammation
  • thrombosis
  • glycoprotein

Fingerprint

Dive into the research topics of 'Platelet GPVI (glycoprotein VI) and thrombotic complications in the venous system'. Together they form a unique fingerprint.

Cite this