Interaction of von Willebrand factor with platelets and the vessel wall

Summary

The initiation of thrombus formation at sites of vascular injury to secure haemostasis after tissue trauma requires the interaction of surface-exposed von Willebrand factor (VWF) with its primary platelet receptor, the glycoprotein (GP) Ib-IX-V complex. As an insoluble component of the extracellular matrix (ECM) of endothelial cells, VWF can directly initiate platelet adhesion. Circulating plasma VWF en-hances matrix VWF activity by binding to structures that become exposed to flowing blood, notably collagen type I and III in deeper layers of the vessel along with microfibrillar collagen type VI in the sub endothelium. Moreover, plasma VWF is required to support platelet-to-platelet adhesion – i. e. aggregation – which promotes thrombus growth and consolidation. For these reasons, understanding how plasma VWF interaction with platelet receptors is regulated, particularly any distinctive features of GPIb binding to soluble as opposed to immobilized VWF, is of paramount importance in vascular biology.

This brief review will highlight knowledge acquired and key problems that remain to be solved to elucidate fully the role of VWF in normal haemostasis and pathological thrombosis.

Zusammenfassung

Zu Beginn der Thrombusbildung in verletzten Gefäßabschnitten muss zur Sicherung der Hämostase nach einem Gewebetrauma der oberflächenexponierte von-Willebrand-Faktor (VWF) mit seinem primären Thrombozytenrezeptor, dem Glykoprotein(GP)-Ib-IXV-Komplex, interagieren. Als unlöslicher Bestandteil der extrazellulären Matrix (EZM) der Endothelzellen kann VWF die Thrombozytenadhäsion direkt auslösen. Im Plasma zirkulierender VWF erhöht die Aktivität des Matrix-VWF durch Bindung an Strukturen, die dem Blutstrom ausgesetzt werden, vor allem Kollagen I und III in tieferen Gefäßwandschichten sowie subendotheliales Kollagen VI der Mikrofibrillen. Außerdem wird der Plasma-VWF für die Adhäsion der Thrombozyten untereinander – d. h. die Aggregation – benötigt, durch die Wachstum und Konsolidierung des Thrombus gefördert werden. Deshalb ist es in der Gefäßbiologie wichtig zu verstehen, wie die Wechselwirkung zwischen Plasma-VWF und Plättchenrezeptoren reguliert wird, besonders alle Merkmale der Bindung von GPIb an löslichen oder gebundenen VWF.

Diese kurze Übersicht beleuchtet die Erkenntnisse und Probleme, die zu lösen sind, um die Rolle des VWF bei der normalen Hämostase und bei pathologischen Thrombosen gänzlich aufzuklären.

Keywords

Von Willebrand factor

Schlüsselwörter

Von-Willebrand-Faktor

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