Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1.
Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) are endothelial cell-specific growth factors. Direct comparison of transgenic mice overexpressing these factors in the skin revealed that the VEGF-induced blood vessels were leaky, whereas those induced by Ang1 were nonleaky. Moreover, vessels in Ang1-overexpressing mice were resistant to leaks caused by inflammatory agents. Coexpression of Ang1 and VEGF had an additive effect on angiogenesis but resulted in leakage-resistant vessels typical of Ang1. Ang1 therefore may be useful for reducing microvascular leakage in diseases in which the leakage results from chronic inflammation or elevated VEGF and, in combination with VEGF, for promoting growth of nonleaky vessels.
Thurston
G
G
Department of Anatomy and Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0452, USA. gavint@itsa.ucsf.edu
Suri
C
C
Smith
K
K
McClain
J
J
Sato
T N
TN
Yancopoulos
G D
GD
McDonald
D M
DM
D042683:Angiopoietin-1; D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000502:physiology; D001665:Binding Sites; D002196:Capillaries / Q000033:anatomy & histology / Q000502:physiology; D002199:Capillary Permeability; D004423:Ear; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced; D018836:Inflammation Mediators / Q000494:pharmacology; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000033:anatomy & histology / Q000502:physiology*; D009149:Mustard Plant; D018919:Neovascularization, Physiologic; D010936:Plant Extracts / Q000494:pharmacology; D037121:Plant Lectins; D010938:Plant Oils; D010946:Plants, Medicinal; D010972:Platelet Activating Factor / Q000494:pharmacology; D012276:Ricin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D012867:Skin / Q000098:blood supply / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014699:Venules / Q000033:anatomy & histology / Q000502:physiology
D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D016228:Endothelial Growth Factors; D018836:Inflammation Mediators; D008222:Lymphokines; D008562:Membrane Glycoproteins; D010936:Plant Extracts; D037121:Plant Lectins; D010938:Plant Oils; D010972:Platelet Activating Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012701:Serotonin; D012276:Ricin; C027793:mustard oil