Interaction of von Willebrand factor with platelets and the vessel wall

Abstract

SummaryThe 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 subendothelium. 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.

Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells

“…vWF is synthesized not only by endothelial cells but also megakaryocytes and stored in platelets; however, experimental evidence shows that the endothelial vWF contribution to haemostasis outweighs that of platelets1011 Soluble plasma vWF, derived from ADAMTS13 processing of the highly multimerized vWF secreted from endothelial cells can bind to substratum-adhered vWF, a homotypic association regulated by shear stress1213. At pathologically high shear rates, soluble vWF can self-associate on collagen coated substrata (a model of the sub-endothelial matrix) and generates, in a concentration-dependent manner, string-like structures capable of recruiting platelets14.…”

Von Willebrand Disease in the elderly: clinical perspectives

“…VWF binds to the glycoprotein GPIbα on the surface of platelets that results in platelet tethering in addition to platelet adherence to vessel wall collagen 10. It also functions as a carrier molecule for FVIII, protecting FVIII from proteolysis and prolonging its half-life in circulation 10,11. Mutations in VWF have been described that affect platelet binding, collagen binding, secretion, and synthesis.…”

Роль Тромбоцитов В Патогенезе Бактериальных Инфекций

“…В физиологических условиях (при отсутствии инфекции) GPIb на поверхности тромбоцитов вза-имодействует с фВ, постоянно присутствующим на Купферовских и клетках эндотелия синусоидов печени, и тромбоциты сканируют внутрисосуди-стую поверхность синусоидов, что является меха-низмом надзора над этими клетками [46].…”