Background:

The angiopoietin (Ang) family of growth factors includes four members, all of which bind to the endothelial receptor tyrosine kinase Tie2. Two of the Angs, Ang-1 and Ang-4, activate the Tie2 receptor, whereas Ang-2 and Ang-3 inhibit Ang-1-induced Tie2 phosphorylation. Angiopoietin-1 (Ang-1) is a secreted growth factor which binds to and activates the Tie-2 receptor tyrosine kinase. The factor enhances endothelial cell survival and capillary morphogenesis, and also limits capillary permeability. Ang-2 binds the same receptor but fails to activate it: hence, it is a natural inhibitor of Ang-1. Ang-2 destabilises capillary integrity, facilitating sprouting when ambient vascular endothelial growth factor (VEGF) levels are high, but causing vessel regression when VEGF levels are low. Tie -1 is a Tie -2 homologue but its ligands are unknown. Angiopoietin and Tie genes are expressed in the mammalian metanephros, the precursor of the adult kidney, where they may play a role in endothelial precursor growth. Angiopoietin 2 is elevated in patients with angiosarcoma. Vaccination against TIE-2 +ve cells appears to reduce atheroma formation in experimental animals. Human and mouse Ang-2 share 85% amino acid sequence identity and are 60% identical to their Ang-1 homologs.