Figure 2.

The angiopoietin/Tie receptor system. Angiopoietin 1 (ANGPT1), released by perivascular cells, is a Tie2 agonist that induces the formation of Tie2 clusters on endothelial cells (ECs) [39]. The phosphorylation of Tie2 leads to the activation of several downstream signaling pathways involved in vessel stability and endothelial barrier function. Thus, Tie2 activation by ANGPT1 promotes EC survival, migration, and proliferation, and inhibits vascular permeability [39,40]. By contrast, ANGPT2, released from EC Weibel–Palade bodies in response to various stimuli [41,42], activates Tie2 only weakly [43] and antagonizes ANGPT1 at the Tie2 receptor. Therefore, ANGPT2 increases vascular permeability and exerts proinflammatory effects [41]. ANGPT1 and/or ANGPT2 are also released from human macrophages [44,45], mast cells [9], and neutrophils [46]. ANGPT2 may also bind to and signal via integrin heterodimers [47,48]. The Tie1, homolog of Tie2, is considered an orphan receptor expressed by ECs.