ANGPTs

The angiopoietins (ANGPTs) are a family of secreted growth factors that regulate blood vessel development, remodeling, and stability. In humans, the best characterized members are ANGPT1 and ANGPT2; ANGPT3 and ANGPT4 are less well defined in humans and show species-specific variation.

ANGPTs share structural features, including an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain, and typically form dimers or higher-order multimers. They signal primarily through the endothelial receptor tyrosine kinase Tie2 (TEK), which mediates their effects on vascular cells.

ANGPT1 activates Tie2 signaling to promote endothelial junction integrity, reduce vascular permeability, and support vessel maturation. ANGPT2, by contrast, acts as a context-dependent antagonist of ANGPT1-Tie2 signaling and facilitates vascular remodeling. In the presence of VEGF, ANGPT2 promotes angiogenesis and permeability; in the absence of VEGF, ANGPT2 can destabilize vessels and contribute to regression.

Expression patterns and roles vary by tissue. ANGPT1 is commonly produced by perivascular cells and supporting cells in various tissues, while ANGPT2 is largely endothelial. Their expression is regulated by hypoxia and inflammatory signals, and they participate in development, tumor angiogenesis, retinopathy, wound healing, and inflammatory diseases.

Therapeutically, targeting the ANGPT–Tie2 axis is an area of interest in cancer and ocular diseases. Agents include ANGPT2 inhibitors and Tie2 modulators, sometimes in combination with VEGF inhibitors, with several candidates evaluated in preclinical and clinical studies.