On the Versatility of Von Willebrand Factor

Abstract

Von Willebrand factor (VWF) is a large multimeric protein, the function of which has been demonstrated to be pivotal to the haemostatic system. Indeed, quantitative and/or qualitative abnormalities of VWF are associated with the bleeding disorder Von Willebrand disease (VWD). Moreover, increased plasma concentrations of VWF have been linked to an increased risk for thrombotic complications. In the previous decades, many studies have contributed to our understanding of how VWF is connected to the haemostatic system, particularly with regard to structure-function relationships. Interactive sites for important ligands of VWF (such as factor VIII, collagen, glycoprotein Ibα, integrin αIIbβ3 and protease ADAMTS13) have been identified, and mutagenesis studies have confirmed the physiological relevance of the interactions between VWF and these ligands. However, we have also become aware that VWF has a more versatile character than previously thought, given its potential role in various non-hemostatic processes, like intimal thickening, tumor cell apoptosis and inflammatory processes. In the presence review, a summary of our knowledge on VWF structure-function relationships is provided in the context of the “classical” haemostatic task of VWF and in perspective of pathological processes beyond haemostasis.

von Willebrand factor regulation of blood vessel formation

“…1 The importance of VWF in hemostasis is illustrated by the fact that its deficiency and/ or abnormality causes von Willebrand disease (VWD), the most frequent inherited bleeding disorder. Over the past 2 decades, other roles for VWF in the vasculature have been identified, including inflammation, permeability, and angiogenesis (reviewed in Rauch et al 2 ). The function of VWF is linked to its interaction with multiple cellular and extracellular proteins and to its ability to coordinate the formation of Weibel-Palade bodies (WPBs).…”

Von Willebrand Factor Interacts with Surface-Bound C1q and Induces Platelet Rolling

“…Whereas the classical functions of VWF are considered to be the initiation of thrombus formation on ruptured surfaces and the stabilization of coagulation factor VIII, a major enhancer of the coagulation cascade, more versatile functions have been elucidated recently, such as intima thickening, tumor cell apoptosis, and inflammatory processes (12). Most of these functions require a particular conformational change in the VWF protein.…”

Molecular suitability of the chacma baboon in human‐targeted Von Willebrand factor directed studies

“…5 The VWF protein contains distinct domains that are arranged as follows: SP-D1-D2-D'-D3-A1-A2-A3-D4-C1-C2-C3-C4-C5-C6-CK. 6,7 The human VWF gene exon 28 encodes for a total of 457 amino acids, starting at His1226 in the D3 domain and ending at Pro1682 in the A3 domain. 4 Thus, exon 28 encodes for the whole A1 and A2 domains, and part of the D3 and A3 domains.…”