Tie2 Receptor Ligands, Angiopoietin-1 and Angiopoietin-2, Modulate VEGF-Induced Postnatal Neovascularization

Angiopoietin-1 (Ang1) has been recently identified as the major physiological ligand for the tyrosine kinase receptor Tie2 and assigned responsibility for recruiting and sustaining periendothelial support cells. Angiopoietin-2 (Ang2) was found to disrupt blood vessel formation in the developing embr...

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Bibliographic Details
Published in:Circulation research 1998-08, Vol.83 (3), p.233-240
Main Authors: Asahara, Takayuki, Chen, Donghui, Takahashi, Tomono, Fujikawa, Koshi, Kearney, Marianne, Magner, Meredith, Yancopoulos, George D, Isner, Jeffrey M
Format: Article
Language:English
Subjects:
Angiopoietin-1
Angiopoietin-2
Animals
Biological and medical sciences
Blood vessels and receptors
Cornea - blood supply
Culture Techniques
Endothelial Growth Factors - metabolism
Enzyme Inhibitors - metabolism
Fundamental and applied biological sciences. Psychology
Humans
Lymphokines - metabolism
Male
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Neovascularization, Physiologic
Proteins - metabolism
Receptor Protein-Tyrosine Kinases - antagonists & inhibitors
Receptor Protein-Tyrosine Kinases - metabolism
Receptor, TIE-2
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Vertebrates: cardiovascular system
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Summary:Angiopoietin-1 (Ang1) has been recently identified as the major physiological ligand for the tyrosine kinase receptor Tie2 and assigned responsibility for recruiting and sustaining periendothelial support cells. Angiopoietin-2 (Ang2) was found to disrupt blood vessel formation in the developing embryo by antagonizing the effects of Ang1 and Tie2 and was thus considered to represent a natural Ang1/Tie2 inhibitor. In vivo effects of either angiopoietin on postnatal neovascularization, however, have not been previously described. Accordingly, we used the cornea micropocket assay of neovascularization to investigate the impact of angiopoietins on neovascularization in vivo. Neither Ang1 nor Ang2 alone promoted neovascularization. Pellets containing vascular endothelial growth factor (VEGF) alone induced corneal neovascularity extending from the limbus across the cornea. Addition of Ang1 to VEGF (Ang1+VEGF) produced an increase in macroscopically evident perfusion of the corneal neovasculature without affecting macroscopic measurements of length (0.58 +/- 0.03 mm) or circumferential neovascularity (136 +/- 10[degree sign]). In contrast, pellets containing Ang2+VEGF promoted significantly longer (0.67 +/- 0.05 mm) and more circumferential (160 +/- 15[degree sign]) neovascularity than VEGF alone or Ang1+VEGF (P
ISSN:0009-7330
1524-4571
DOI:10.1161/01.res.83.3.233