Figure 2.

Therapeutic targets in vascular malformation syndromes with possible relevance to von Willebrand disease angiodysplasia. There appear to be multiple overlapping routes to vascular malformations which may help to identify overlaps between von Willebrand disease (VWD) and other vascular abnormality syndromes. The place of von Willebrand factor (VWF) in this web of molecular pathways remains unclear but may point to therapeutic alternatives in VWD. The figure shows current therapeutic alternatives that have targets within established VWF pathways (red) and those within pathways of other established vascular malformation syndromes (gray). HMWM: high molecular weight multimers; Angpt2: angiopoetin-2; Tie2: tyrosine kinase receptor; VEGF: vascular endothelial growth factor; VEGFR2: vascular endothelial growth factor receptor 2; RAS: rat sarcoma; MEK: mitogen-activated protein kinase kinase 1; ERK: extracellular signal-regulated kinase; PI3K: phosphoinositide 3 kinase; AKT: serine-thre-onine protein kinase; mTOR: mammalian target of rapamycin; BMP: bone morphogenetic protein; ALK1: activin receptor-like kinase 1; PTEN: phosphatase and tensin homolog; SMAD: mothers against decapentaplegic homolog; EC: endothelial cell.