Ang2

Angiopoietin-2 (Ang2) is a secreted glycoprotein in the angiopoietin family that binds the Tie2 receptor (TEK) on endothelial cells. It is encoded by the ANGPT2 gene and is produced mainly by endothelial cells. Ang2 is stored in Weibel-Palade bodies and released in response to inflammatory stimuli, hypoxia, or other stress signals.

Ang2 plays a context-dependent role in blood vessel remodeling. When Ang2 engages Tie2, it generally destabilizes established vessels by reducing pericyte coverage and loosening intercellular junctions. This destabilization makes the endothelium more responsive to pro-angiogenic signals. In the presence of vascular endothelial growth factor (VEGF), Ang2 promotes angiogenesis; in the absence of VEGF, Ang2 can contribute to vessel regression and pruning by enabling endothelial cell death.

Ang1, another angiopoietin family member, activates Tie2 to stabilize vessels. Ang2 can act as a competitive antagonist of Ang1, shifting the balance toward remodeling or leakiness. Regulation of Ang2 involves inflammatory cytokines and hypoxic conditions and its effects are highly tissue- and context-dependent.

Clinically, elevated Ang2 levels have been observed in sepsis, acute lung injury and acute respiratory distress syndrome, as well as in various cancers, where they are associated with vascular leak and poor outcomes. Consequently, Ang2 is explored as a therapeutic target in oncology and inflammatory diseases, with strategies that aim to inhibit Ang2 alone or in combination with VEGF blockade.