Upregulation of Ang2 expression and enhanced secretion of Ang2 in ECs are highly reactive processes that occur in any unstable and stimulatory conditions, including acute inflammation, chronic hyperglycemia, cerebral cavernous malformation and excess of vascular stimulating factors and cytokines, which definitively contribute to further exacerbation of vascular destabilization in a positive feedback manner57, 58, 59, 60. Here, ANGPT2 is linked to famililal cerebral cavernous malformations.