Figure 1.

Model of von Willebrand factor regulation of angiogenesis. von Willebrand factor (VWF) is likely to modulate angiogenesis via various pathways. VWF is critical to the formation of Weibel-Palade bodies that store the growth factor angiopoetin-2 (Angpt2). Loss of VWF leads to increased Angpt2 release from endothelial cells and subsequent increased Angpt2 signaling. Upon its release, Angpt2 can bind the tyrosine kinase receptor Tie2 which promotes angiogenesis by synergizing with vascular endothelial growth factor (VEGF) signaling. VWF can also bind to integrin αvβ3 on the endothelial cell surface which modulates VEGF receptor 2 (VEGFR2) signaling downstream. However, loss of VWF decreases αvβ3 surface expression which might modify sensitivity to VEGF/VEGFR2 signaling. The ability of VWF to bind multiple receptors and ligands may result in VWF-dependent cross-linking of cell surface receptors αvβ3, Tie2 and VEGFR2, which may explain why its effects in angiogenesis are dependent on high molecular weight multimers. EC: endothelial cell; HMWM: high molecular weight multimer; WPB: Weibel-Palade body.