title: Beta3-integrin regulates vascular endothelial growth factor-A-dependent permeability.
abstract: OBJECTIVE
  Beta3-integrin deficiency has been implicated in increasing levels of Flk-1 expression on endothelial cells and enhancing vascular endothelial growth factor (VEGF)-induced angiogenesis. We determined the role of beta3-integrin in mediating VEGF-A-induced blood vessel permeability through Flk-1.
  
  
  RESULTS
  Using the Miles assay, we demonstrated that VEGF-A-induced plasma leakage was enhanced in beta3-null mice when compared with wild-type controls. This was not caused by any changes in blood vessel structure (as detected by light or electron microscopy) or by changes in endothelial cell-cell adhesion proteins (as determined by Western blot analysis, flow cytometry, and immunofluorescence). Circulating levels of VEGF, baseline blood vessel leakage, and leakage in response to an acute inflammatory stimulus were identical in wild-type and beta3-null mice. However, VEGF-A-induced leakage was abolished in beta3-null mice by the inhibition of Flk-1, indicating that the elevated levels of Flk-1 on beta3-null endothelial cells enhance VEGF-A-induced permeability.
  
  
  CONCLUSIONS
  beta3-integrin-deficiency increases the sensitivity of endothelial cells to VEGF-A by elevating Flk-1 expression and, as a consequence, enhances VEGF-A-mediated permeability.
authors.affiliation: Cell Adhesion and Disease/Tumour Biology Laboratory, Cancer Research UK Clinical Centre, Queen Mary's School of Medicine & Dentistry at Barts & The London, John Vane Science Centre, London, United Kingdom. s.d.robinson@cancer.org.uk
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Robinson
authors.forename: Louise E
authors.initials: LE
authors.lastname: Reynolds
authors.forename: Lorenza
authors.initials: L
authors.lastname: Wyder
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hicklin
authors.forename: Kairbaan M
authors.initials: KM
authors.lastname: Hodivala-Dilke
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology; D007249:Inflammation / Q000473:pathology; D039661:Integrin beta3 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D039661:Integrin beta3; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2