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.