von Willebrand factor: the old, the new and the unknown

Abstract

Summary. von Willebrand factor (VWF) is a protein best known from its critical role in hemostasis. Indeed, any dysfunction of VWF is associated with a severe bleeding tendency known as von Willebrand disease (VWD). Since the first description of the disease by Erich von Willebrand in 1926, remarkable progress has been made with regard to our understanding of the pathogenesis of this disease. The cloning of the gene encoding VWF has allowed numerous breakthroughs, and our knowledge of the epidemiology, genetics and molecular basis of VWD has been rapidly expanding since then. These studies have taught us that VWF is rather unique in terms of its multimeric structure and the unusual mechanisms regulating its participation in the hemostatic process. Moreover, it has become increasingly clear that VWF is a more all‐round protein than originally thought, given its involvement in several pathologic processes beyond hemostasis. These include angiogenesis, cell proliferation, inflammation, and tumor cell survival. In the present article, an overview of advances concerning the various structural and functional aspects of VWF will be provided.

Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis

“…14,26 It has been documented that VWF:Ag is released by the ECs and that under pathologic conditions, VWF serves as a biomarker of endothelial damage and dysfunction 14,26 and is involved in hemostasis and inflammatory activation. 27,28 The specific mechanism of increased VWF:Ag in AL amyloidosis probably implicates ECs, because these are the most important producer of these molecules.…”

ADAMTS13 controls vascular remodeling by modifying VWF reactivity during stroke recovery

“…37 Of the 10 genes analyzed, Ang-2 and Gal-3 showed the largest alteration in gene expression, with more than 5.5-fold downregulation in Adamts13 2/2 mice ( Figure 4A). In contrast, VWF deficiency resulted in a significant increase in Ang-2 and Gal-3 levels in the isolated brain microvessels ( Figure 4B).…”

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

“…The vWF allows platelets to adhere to ECs and can travel via blood to sites of blood vessel injury and attach to exposed collagen fibers. These functions ascribe vWF an important role in the responses of ECs, which cause coagulation, form thrombi, and repair damaged tissue (for a detailed review on vWF, see Lenting et al, 2012;De Ceunynck et al, 2013).…”