The Tie1 and Tie2 receptor tyrosine kinases and the angiopoietin growth factor ligands, Ang1-4, are essential for vascular maturation. Targeted deletion of any of the Tie1,Tie2 or Ang1 genes in mice results in embryonic lethality during embryonic days 9.5–13.5. The receptors are expressed mainly in endothelial cells, while Ang1 is produced by perivascular cells and thought to stabilize quiescent endothelium. In contrast, Ang2 is secreted by endothelial cells in angiogenic vasculature, such as in tumors, leading to destabilization of the endothelium. Ang1 multimers stimulate the phosphorylation of Tie1 and Tie2, while Ang2 functions as a context-dependent agonist/antagonist for Tie2. Ang1 has promising vascular protective effects as an anti-permeability, anti-inflammatory and cell survival factor, but it can also induce vessel remodelling. The angiopoietin-Tie signalling pathway may be a therapeutically useful target in the treatment of a number of diseases, including oedema, endotoxaemia, transplant arteriosclerosis and cancer.
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Saharinen, P., Eklund, L., Alitalo, K. (2008). Angiopoietins and Tie Receptors. In: Figg, W.D., Folkman, J. (eds) Angiogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71518-6_10
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