Von Willebrand factor, angiodysplasia and angiogenesis

Anna M Randi, Mike A Laffan, Richard D Starke, Anna M Randi, Mike A Laffan, Richard D Starke

Abstract

The large multimeric glycoprotein Von Willebrand factor (VWF) is best known for its role in haemostasis; however in recent years other functions of VWF have been identified, indicating that this protein is involved in multiple vascular processes. We recently described a new role for VWF in controlling angiogenesis, which may have significant clinical implications for patients with Von Willebrand disease (VWD), a genetic or acquired condition caused by the deficiency or dysfunction of VWF. VWD can be associated with angiodysplasia, a condition of degenerative blood vessels often present in the gastrointestinal tract, linked to dysregulated angiogenesis. Angiodysplasia can cause severe intractable bleeding, often refractory to conventional VWD treatments. In this review we summarise the evidence showing that VWF controls angiogenesis, and review the angiogenic pathways which have been implicated in this process. We discuss the possible mechanisms though which VWF regulates angiopoietin-2 (Ang-2) and integrin αvβ3, leading to signalling through vascular endothelial growth factor receptor-2 (VEGFR2), one of the most potent activators of angiogenesis. We also review the evidence that links VWF with angiodysplasia, and how the newly identified function of VWF in controlling angiogenesis may pave the way for the development of novel therapies for the treatment of angiodysplasia in congenital VWD and in acquired conditions such as Heyde syndrome.

Figures

Figure 1
Figure 1
VWF and Angiopoietin-2 (Ang-2) co-localise in Weibel Palade Bodies (WPB) in Human Umbilical Vein Endothelial Cells (HUVEC). WPB are visible as discrete rod-like structures inside the cell. See text for details.
Figure 2
Figure 2
VWF controls angiogenesis through intracellular and extracellular pathways, involving Ang-2 and integrin αvβ3 respectively. These pathways converge to regulate angiogenesis through VEGF Receptor 2 signalling – see text for details.

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