title: Important role of Nox4 type NADPH oxidase in angiogenic responses in human microvascular endothelial cells in vitro.
abstract: OBJECTIVE
  Redox signaling mediated by Nox2-containing NADPH oxidase has been implicated in angiogenic responses both in vitro and in vivo. Because Nox4 type NADPH oxidase is also highly expressed in endothelial cells, we studied the role of Nox4 in angiogenic responses in human endothelial cells in culture.
  
  
  RESULTS
  Inhibition of Nox4 expression by small interfering RNA reduced angiogenic responses as assessed by the tube formation and wound healing assays, in both human microvascular and umbilical vein endothelial cells. Overexpression of wild-type Nox4 enhanced, whereas expression of a dominant negative form of Nox4 suppressed the angiogenic responses in endothelial cells. These effects were mimicked by exogenous H2O2 and the antioxidant compound ebselen, respectively. Overexpression of Nox4 enhanced receptor tyrosine kinase phosphorylation and the activation of extracellular signal-regulated kinase (Erk). Inhibition of the Erk pathway reduced the endothelial angiogenic responses. Nox4 expression also promotes proliferation and migration of endothelial cells, and reduced serum deprivation-induced apoptosis.
  
  
  CONCLUSIONS
  Nox4 type NADPH oxidase promotes endothelial angiogenic responses, at least partly, via enhanced activation of receptor tyrosine kinases and the downstream Erk pathway.
authors: Bernard O'Brien Institute of Microsurgery, University of Melbourne, Victoria 3065, Australia.
authors: Srinivasa Raju
authors: SR
authors: Datla
authors: Hitesh
authors: H
authors: Peshavariya
authors: Gregory J
authors: GJ
authors: Dusting
authors: Kalyankar
authors: K
authors: Mahadev
authors: Barry J
authors: BJ
authors: Goldstein
authors: Fan
authors: F
authors: Jiang
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human