[PDF][PDF] Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1

NW Gale, G Thurston, SF Hackett, R Renard, Q Wang… - Developmental cell, 2002 - cell.com
NW Gale, G Thurston, SF Hackett, R Renard, Q Wang, J McClain, C Martin, C Witte…
Developmental cell, 2002cell.com
VEGF and Angiopoietin-1 requisitely collaborate during blood vessel development. While
Angiopoietin-1 obligately activates its Tie2 receptor, Angiopoietin-2 can activate Tie2 on
some cells, while it blocks Tie2 activation on others. Our analysis of mice lacking
Angiopoietin-2 reveals that Angiopoietin-2 is dispensable for embryonic vascular
development but is requisite for subsequent angiogenic remodeling. Unexpectedly, mice
lacking Angiopoietin-2 also exhibit major lymphatic vessel defects. Genetic rescue with …
Abstract
VEGF and Angiopoietin-1 requisitely collaborate during blood vessel development. While Angiopoietin-1 obligately activates its Tie2 receptor, Angiopoietin-2 can activate Tie2 on some cells, while it blocks Tie2 activation on others. Our analysis of mice lacking Angiopoietin-2 reveals that Angiopoietin-2 is dispensable for embryonic vascular development but is requisite for subsequent angiogenic remodeling. Unexpectedly, mice lacking Angiopoietin-2 also exhibit major lymphatic vessel defects. Genetic rescue with Angiopoietin-1 corrects the lymphatic, but not the angiogenesis, defects, suggesting that Angiopoietin-2 acts as a Tie2 agonist in the former setting, but as an antagonist in the latter setting. Our studies define a vascular growth factor whose primary role is in postnatal angiogenic remodeling and also demonstrate that members of the VEGF and Angiopoietin families collaborate during development of the lymphatic vasculature.
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