The Cytosolic NADPH Oxidase Subunit NoxO1 Promotes an Endothelial Stalk Cell Phenotype

Ralf P. Brandes, Sabine Harenkamp, Christoph Schürmann, Ivana Josipovic, Beliza Rashid, Flavia Rezende, Oliver Löwe, Franziska Moll, Jeremy Epah, Jeanette Eresch, Arnab Nayak, Irakli Kopaliani, Cornelia Penski, Michel Mittelbronn, Norbert Weissmann, Katrin Schröder*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)


Objective - Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases contribute to angiogenesis and vascular repair. NADPH oxidase organizer 1 (NoxO1) is a cytosolic protein facilitating assembly of constitutively active NADPH oxidases. We speculate that NoxO1 also contributes to basal reactive oxygen species formation in the vascular system and thus modulates angiogenesis. Approach and Results - A NoxO1 knockout mouse was generated, and angiogenesis was studied in cultured cells and in vivo. Angiogenesis of the developing retina and after femoral artery ligation was increased in NoxO1 -/- when compared with wild-type animals. Spheroid outgrowth assays revealed greater angiogenic capacity of NoxO1 -/- lung endothelial cells (LECs) and a more tip-cell-like phenotype than wild-type LECs. Usually signaling by the Notch pathway switches endothelial cells from a tip into a stalk cell phenotype. NoxO1 -/- LECs exhibited attenuated Notch signaling as a consequence of an attenuated release of the Notch intracellular domain on ligand stimulation. This release is mediated by proteolytic cleavage involving the α-secretase ADAM17. For maximal activity, ADAM17 has to be oxidized, and overexpression of NoxO1 promoted this mode of activation. Moreover, the activity of ADAM17 was reduced in NoxO1 -/- LECs when compared with wild-type LECs. Conclusions - NoxO1 stimulates α-secretase activity probably through reactive oxygen species-mediated oxidation. Deletion of NoxO1 attenuates Notch signaling and thereby promotes a tip-cell phenotype that results in increased angiogenesis.

Original languageEnglish
Pages (from-to)1558-1565
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number8
Publication statusPublished - 1 Aug 2016
Externally publishedYes


  • ADAM17 protein
  • Notch
  • NoxO1 protein, mouse
  • angiogenesis effect
  • dibenzazepine
  • reactive oxygen species


Dive into the research topics of 'The Cytosolic NADPH Oxidase Subunit NoxO1 Promotes an Endothelial Stalk Cell Phenotype'. Together they form a unique fingerprint.

Cite this