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.
D043925:Angiogenesis Inducing Agents / Q000502:physiology*; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D019521:Body Patterning; D002915:Chylous Ascites / Q000235:genetics / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D004487:Edema / Q000235:genetics / Q000473:pathology; D005123:Eye / Q000098:blood supply; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006720:Homozygote; D008208:Lymphatic System / Q000254:growth & development* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012171:Retinal Vessels / Q000473:pathology
D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; D018076:DNA, Complementary; D008562:Membrane Glycoproteins