Von Willebrand Factor and Platelet Glycoprotein Ib: A Thromboinflammatory Axis in Stroke.

Frederik Denorme,Karen Vanhoorelbeke,Simon F De Meyer

doi:10.3389/fimmu.2019.02884

Frederik Denorme, Karen Vanhoorelbeke + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2019.02884

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Abstract

von Willebrand factor (VWF) and platelets are key mediators of normal hemostasis. At sites of vascular injury, VWF recruits platelets via binding to the platelet receptor glycoprotein Ibα (GPIbα). Over the past decades, it has become clear that many hemostatic factors, including VWF and platelets, are also involved in inflammatory processes, forming intriguing links between hemostasis, thrombosis, and inflammation. The so-called “thrombo-inflammatory” nature of the VWF-platelet axis becomes increasingly recognized in different cardiovascular pathologies, making it a potential therapeutic target to interfere with both thrombosis and inflammation. In this review, we discuss the current evidence for the thrombo-inflammatory activity of VWF with a focus on the VWF-GPIbα axis and discuss its implications in the setting of ischemic stroke.

Highlights

Specialty section: This article was submitted to Inflammation, a section of the journal Frontiers in Immunology
von Willebrand factor (VWF) is synthesized as a pre-pro-VWF that consists of a 22 amino acid signal peptide, a 741 amino acid propeptide (D1-D2) and a mature subunit of 2,050 amino acids [6]
VWF is either constitutively secreted into the blood or is stored in endothelial Weibel-Palade bodies (WPB) and platelet α-granules, from which VWF is locally released via regulated secretion [8]

Summary

Introduction

Specialty section: This article was submitted to Inflammation, a section of the journal Frontiers in Immunology. The GPIbα-VWF and GPVI/α2β1collagen interactions induce downstream intracellular platelet signaling leading to activation of platelet αIIbβ3, which mediates further stable adhesion and aggregation via binding to fibrinogen and VWF. Activated platelets bind to VWF and can interact via Pselectin or GPIbα with leukocytes, promoting local adhesion of inflammatory cells [26].

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Conclusion