title: Vitronectin regulation of vascular endothelial growth factor-mediated angiogenesis.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) plays a key role in regulating angiogenesis, and this process is largely dependent on the newly formed extracellular matrix (ECM). The levels of vitronectin (VN) are increased in patients with various cardiovascular diseases. A role for VN in regulating VEGF-induced angiogenesis has not been previously reported. We tested the hypothesis that VN regulates VEGFR-2 activation via effects on αvβ3, thus contributing to angiogenesis.
  
  
  METHODS
  We used a 3-dimensional angiogenesis assay, and examined the effects of VN on VEGF-mediated angiogenesis in aortic endothelial cells (ECs) isolated from wild-type and VN-deficient mice.
  
  
  RESULTS
  The addition of multimeric VN significantly enhanced VEGF-induced increases in EC migration and capillary formation. In vitro, Vn(-/-) ECs migrated significantly slower than wild-type ECs. The addition of VN to Vn(-/-) ECs increased EC migration and augmented the promigratory effect of VEGF in a manner that involved VEGFR-2 and Src signaling. Analysis of the mechanisms involved revealed that multimeric VN, but not monomeric VN, binds VEGF and enhances VEGF-induced VEGFR-2/Src activation in ECs.
  
  
  CONCLUSIONS
  These results underscore the importance of VN in the regulation of angiogenesis induced by VEGF.
authors.affiliation: Drug Discovery Research Center, Luzhou Medical College, Luzhou, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Mao
authors.initials: M
authors.lastname: Luo
authors.forename: Meiping
authors.initials: M
authors.lastname: Ren
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.forename: Jiyi
authors.initials: J
authors.lastname: Xia
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Min
authors.initials: M
authors.lastname: Zeng
authors.forename: Kai
authors.initials: K
authors.lastname: Yan
authors.forename: Tingting
authors.initials: T
authors.lastname: Luo
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D019096:Vitronectin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D039302:Integrin alphaVbeta3; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019096:Vitronectin; D040301:Vascular Endothelial Growth Factor Receptor-2; D019061:src-Family Kinases