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

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.

Pubmed ID: 12361603

Authors

  • Gale NW
  • Thurston G
  • Hackett SF
  • Renard R
  • Wang Q
  • McClain J
  • Martin C
  • Witte C
  • Witte MH
  • Jackson D
  • Suri C
  • Campochiaro PA
  • Wiegand SJ
  • Yancopoulos GD

Journal

Developmental cell

Publication Data

September 3, 2002

Associated Grants

None

Mesh Terms

  • Angiogenesis Inducing Agents
  • Angiopoietin-1
  • Angiopoietin-2
  • Animals
  • Body Patterning
  • Chylous Ascites
  • DNA, Complementary
  • Edema
  • Eye
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Homozygote
  • Lymphatic System
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Neovascularization, Physiologic
  • Promoter Regions, Genetic
  • Retinal Vessels