Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo.
Modulation of Tie2 receptor activity by its angiopoietin ligands is crucial for angiogenesis, blood vessel maturation, and vascular endothelium integrity. It has been proposed that angiopoietins 1 (Ang1) and 2 (Ang2) are pro- and anti-angiogenic owing to their respective agonist and antagonist signaling action through the Tie2 receptor. The function of Ang2 has remained controversial, however, with recent reports suggesting that in some circumstances, it may be pro-angiogenic. We have examined this issue using the transient ocular microvessel network called the pupillary membrane as a unique in vivo model for studying the effects of vascular regulators. We show that in vivo, in the presence of endogenous vascular endothelial growth factor (VEGF)-A, Ang2 promotes a rapid increase in capillary diameter, remodeling of the basal lamina, proliferation and migration of endothelial cells, and stimulates sprouting of new blood vessels. By contrast, Ang2 promotes endothelial cell death and vessel regression if the activity of endogenous VEGF is inhibited. These observations support a model for regulation of vascularity where VEGF can convert the consequence of Ang2 stimulation from anti- to pro-angiogenic.
Lobov
Ivan B
IB
Division of Developmental Biology, Department of Ophthalmology, Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
Brooks
Peter C
PC
Lang
Richard A
RA
D042702:Angiopoietin-2; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002196:Capillaries / Q000166:cytology* / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003315:Cornea / Q000098:blood supply*; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D042702:Angiopoietin-2; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D008222:Lymphokines; D011506:Proteins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors