angiopoietins

Angiopoietins are a family of secreted vascular growth factors that regulate angiogenesis, vessel maturation, and vascular stability through signaling via the Tie2 receptor (TEK) on endothelial cells. The best characterized members in humans are ANGPT1 and ANGPT2; ANGPT4 is present in several species and its status in humans is less well defined.

ANGPT1 acts as a Tie2 agonist, promoting endothelial cell survival, tightening intercellular junctions, and reducing vascular permeability to stabilize mature blood vessels. ANGPT2 binds Tie2 with lower agonist activity and can antagonize ANGPT1 signaling; its effects are highly context dependent. In the presence of vascular endothelial growth factor (VEGF), ANGPT2 facilitates angiogenic remodeling and sprouting, whereas in the absence of VEGF it can promote vessel regression and destabilization.

Expression and release: ANGPT2 is stored in Weibel-Palade bodies in endothelial cells and released in response to inflammatory stimuli or hypoxia; ANGPT1 is produced by pericytes and other supporting cells in the vasculature and maintains basal Tie2 signaling. The balance between ANGPT1 and ANGPT2 influences vascular quiescence versus remodeling.

Clinical relevance: Altered angiopoietin signaling is implicated in cancer angiogenesis, diabetic retinopathy, sepsis, and inflammatory diseases. Therapeutic strategies under investigation target ANGPT2 or Tie2 signaling to modulate vessel stability and angiogenesis, and ANGPT2 levels can serve as a biomarker of endothelial dysfunction in critical illness.