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The yin, the yang, and the Angiopoietin-1
Pipsa Saharinen, Kari Alitalo
Pipsa Saharinen, Kari Alitalo
Published May 23, 2011
Citation Information: J Clin Invest. 2011;121(6):2157-2159. https://doi.org/10.1172/JCI58196.
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Commentary

The yin, the yang, and the Angiopoietin-1

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Abstract

Twenty years after the discovery of the vascular endothelial Tie receptor tyrosine kinases and 15 years after the discovery of the Tie2 ligand, angiopoietin-1 (Angpt1, also known as Ang1), a study published in the current issue of the JCI reveals an unexpected loss-of-function phenotype of mice conditionally deleted of the Angpt1 gene. The results suggest that Angpt1 is needed as a vascular stabilizing factor that organizes and limits the angiogenesis response and protects from pathological consequences, such as tissue fibrosis.

Authors

Pipsa Saharinen, Kari Alitalo

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Figure 1

The Angpt-Tie system in stable vessels and sprouting angiogenesis.

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The Angpt-Tie system in stable vessels and sprouting angiogenesis.
In st...
In stable vessels, Angpt1 is produced by pericytes, Tie2 is activated in endothelial cells, and Angpt2 is stored in Weibel-Palade bodies. However, the data by Jeansson et al. in this issue of the JCI indicates that Angpt1 function is not necessary for normal vascular physiology (7), although Tie2 has been found to be constitutively phosphorylated in quiescent endothelium (6). In vessels undergoing angiogenesis in response to VEGF secreted by nearby hypoxic cells, Angpt2 is expressed predominantly in the tip cells of angiogenic sprouts, where it may regulate cell-matrix interactions by binding to integrins and connective tissue matrix. The Tie2 receptor is expressed in the stalk cells, which become coated with pericytes and the basement membrane matrix that accumulates in between the cells in the stabilization phase of angiogenesis. Angpt1, from the perivascular cells, interacts with the Tie2 receptor. In this context, Angpt1 is necessary for the stabilization of the newly formed vessels, for attenuation of angiogenesis, and for limiting the production of excess of connective tissue. Whether Angpt2 counteracts the Angpt1-induced Tie2 activation in the stalk cells located behind the angiogenic tip cell area is as yet not clear. Angpt2 may also facilitate leukocyte adhesion to the endothelium of newly forming sprouts.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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