The unfolded von Willebrand factor response in bloodstream: the self-association perspective

von Willebrand factor (vWF) is a multimeric glycoprotein essential for hemostasis aftervascular injury, which modulates platelet-surface and platelet-platelet interactions by linkingplatelet receptors to the extracellular matrix and to each other. The crucial role of vWF inplatelet function is particularly apparent when hemodynamic conditions create blood flowwith high shear stress. Through multiple functional domains, vWF mediates the attachment ofplatelets to exposed tissues, where immobilized vWF is able to support a homotypic and/orheterotypic self-association. The self-association of vWF is also supported by a rapidlyexpanding reservoir of novel evidences that the thiol/disulfide exchange regulates vWFmultimer size in the blood circulation. Moreover, in addition to proteolysis and reduction ofADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif,member 13), the regulation of vWF multimer size and self-association may depend on adisulfide bond reductase activity ascribed to thrombospondin-1 (TSP-1). Along with theclassical signaling pathways in activated platelets, evidence is emerging that lipid rafts alsoplay important roles in various phases of hemostasis and thrombosis and facilitate theinteraction between the key signaling molecules. Developments in these areas will refine ourunderstanding of the role played by vWF self-association in physiological hemostasis andpathological thrombosis.

via Journal of Hematology & Oncology