AngiopoietinsTie2

The Angiopoietins-Tie2 axis refers to the signaling interactions between the angiopoietin ligands and the endothelial receptor tyrosine kinase Tie2 (also known as TEK). The core ligands are Angiopoietin-1 (Angpt1), Angiopoietin-2 (Angpt2), and, in some species, Angiopoietin-4 (Angpt4). This axis regulates blood vessel maturation, stability, and permeability, and it plays a central role in vascular remodeling during development as well as in adult tissue responses to injury or inflammation.

Tie2 is predominantly expressed on endothelial cells. Angpt1 is typically produced by perivascular cells such as pericytes and acts as a Tie2 agonist to promote vessel stabilization and anti-inflammatory, anti-permeability effects. Angpt2 is often stored in endothelial cell Weibel-Palade bodies and released in response to signals of vascular remodeling or stress; its effect on Tie2 is context-dependent and can function as an antagonist of Angpt1-Tie2 signaling, promoting vessel destabilization and leakage, or act as a partial agonist in certain environments, particularly when vascular endothelial growth factor (VEGF) is present.

Functionally, Angpt1-Tie2 signaling supports endothelial cell survival, maintains barrier integrity, and facilitates pericyte recruitment and vessel maturation. Angpt2-mediated destabilization can enable remodeling and sprouting in development or in pathological angiogenesis, but excessive Angpt2 activity is associated with vascular leakage and inflammatory escalation in diseases.

Clinical and research implications center on modulating this axis to normalize or stabilize vasculature. Therapeutic strategies include Angpt2 inhibition, Angpt1 mimetics, or Tie2-activating agents, with several candidates investigated in preclinical and clinical studies for cancer, inflammatory diseases, and ocular neovascular disorders.