The role of the Angiopoietins in vascular morphogenesis

• Published in: Angiogenesis (London) Vol. 12; no. 2; pp. 125 - 137
• Main Authors: Thomas, Markus, Augustin, Hellmut G.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-06-2009; Springer Nature B.V
• Subjects: Angiopoietins - metabolism; Animals; Biomedical and Life Sciences; Biomedicine; Blood Vessels - embryology; Blood Vessels - metabolism; Blood Vessels - pathology; Cancer Research; Cardiology; Cell Biology; Humans; Ligands; Morphogenesis; Oncology; Ophthalmology; Original Paper; Receptors, TIE - chemistry; Receptors, TIE - metabolism; Signal Transduction; Angiogenesis; Tie; Endothelial cell; Angiopoietin
• ISSN: 0969-6970; 1573-7209
• DOI: 10.1007/s10456-009-9147-3

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The Angiopoietin/Tie system acts as a vascular specific ligand/receptor system to control endothelial cell survival and vascular maturation. The Angiopoietin family includes four ligands (Angiopoietin-1, Angiopoietin-2 and Angiopoietin-3/4) and two corresponding tyrosine kinase receptors (Tie1 and Tie2). Ang-1 and Ang-2 are specific ligands of Tie2 binding the receptor with similar affinity. Tie2 activation promotes vessel assembly and maturation by mediating survival signals for endothelial cells and regulating the recruitment of mural cells. Ang-1 acts in a paracrine agonistic manner inducing Tie2 phosphorylation and subsequent vessel stabilization. In contrast, Ang-2 is produced by endothelial cells and acts as an autocrine antagonist of Ang-1-mediated Tie2 activation. Ang-2 thereby primes the vascular endothelium to exogenous cytokines and induces vascular destabilization at higher concentrations. Ang-2 is strongly expressed in the vasculature of many tumors and it has been suggested that Ang-2 may act synergistically with other cytokines such as vascular endothelial growth factor to promote tumor-associated angiogenesis and tumor progression. The better mechanistic understanding of the Ang/Tie system is gradually paving the way toward the rationale exploitation of this vascular signaling system as a therapeutic target for neoplastic and non-neoplastic diseases.