Functional inhibition of secreted angiopoietin: a novel role for angiopoietin 1 in coronary vessel patterning

Biochemical and Biophysical Research Communications
Nicole L WardDaniel J Dumont

Abstract

The angiopoietins are a family of growth factors critical for development and maintenance of the vasculature. The primary amino acid sequence of the angiopoietins predicts that they are comprised of a coiled-coiled and a fibrinogen-like domain. The coiled-coiled domain mediates ligand multimerization, whereas the fibrinogen domain engages the receptor. This multimerization is required to elicit a ligand-mediated biological effect via activation of their receptor Tie2. In vitro and in vivo knockout studies have suggested that the angiopoietins are chemotactic for endothelial cells. We were interested in ascertaining whether the angiopoietins have this activity within the animal proper. To accomplish this we engineered a dominant-interfering form of angiopoietin (Ang) 1, called Ang1cc. Ang1cc contains the coiled-coiled domain, which can heterodimerize with other angiopoietins produced in the same cell. We show that Ang1cc can inhibit Tie2 activation and can inhibit Ang1 activity in vitro and in vivo.

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Citations

Feb 24, 2009·Nature Reviews. Molecular Cell Biology·Hellmut G AugustinKari Alitalo
Nov 26, 2008·The Journal of Biological Chemistry·Chuanxi CaiJianjie Ma
Oct 23, 2008·Tissue Engineering. Part a·Paul Van SlykeDan Dumont
Apr 4, 2009·The American Journal of Pathology·Julie A WolframNicole L Ward
Jul 1, 2009·International Journal of Experimental Pathology·Nicola SmartPaul R Riley
Jan 30, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew JohnstonNicole L Ward
Mar 17, 2005·The Journal of Biological Chemistry·Kyung-Tae KimGou Young Koh

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