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Angiopoietin-1 is essential in mouse vasculature during development and in response to injury
Marie Jeansson, … , Mark Henkelman, Susan E. Quaggin
Marie Jeansson, … , Mark Henkelman, Susan E. Quaggin
Published May 23, 2011
Citation Information: J Clin Invest. 2011;121(6):2278-2289. https://doi.org/10.1172/JCI46322.
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Research Article

Angiopoietin-1 is essential in mouse vasculature during development and in response to injury

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Abstract

Angiopoietin-1/Tek signaling is a critical regulator of blood vessel development, with conventional knockout of angiopoietin-1 or Tek in mice being embryonically lethal due to vascular defects. In addition, angiopoietin-1 is thought to be required for the stability of mature vessels. Using a Cre-Lox conditional gene targeting approach, we have studied the role of angiopoietin-1 in embryonic and adult vasculature. We report here that angiopoietin-1 is critical for regulating both the number and diameter of developing vessels but is not required for pericyte recruitment. Cardiac-specific knockout of angiopoietin-1 reproduced the phenotype of the conventional knockout, demonstrating that the early vascular abnormalities arise from flow-dependent defects. Strikingly, deletion in the entire embryo after day E13.5 produced no immediate vascular phenotype. However, when combined with injury or microvascular stress, angiopoietin-1 deficiency resulted in profound organ damage, accelerated angiogenesis, and fibrosis. These findings redefine our understanding of the biological roles of angiopoietin-1: it is dispensable in quiescent vessels but has a powerful ability to modulate the vascular response after injury.

Authors

Marie Jeansson, Alexander Gawlik, Gregory Anderson, Chengjin Li, Dontscho Kerjaschki, Mark Henkelman, Susan E. Quaggin

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Figure 2

Angpt1 is critical in early vascular development.

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Angpt1 is critical in early vascular development.
Simplification of the ...
Simplification of the cardiac trabeculation pattern of E10.5 Angpt1del/del embryos as shown by immunohistochemistry for (A) Ng2 (scale bar: 100 μm) and (B) Desmin (scale bar: 100 μm). (C) Dissection microscope photos show that Angpt1del/del embryos are markedly growth restricted at E10.5 and have disorganized vasculature as evident in embryos carrying a Kdr-GFP transgene reporter (scale bar: 1 mm).

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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