TIE1 and vascular malformation: MMP-9 is a key downstream consequence of VEGF and Ang-2 activity, contributing to the angiogenic phenotype 21, whereas Ang-2/Tie pathway is also associated with Notch signalling 22 Taken together, the action of these factors alone is not sufficient to explain the complex patterning of the brain AVMS; many factors or pathways may be involved in the development of vascular malformations.