Novel role of NADPH oxidase in angiogenesis and stem/progenitor cell function

Masuko Ushio-Fukai, Norifumi Urao

Research output: Contribution to journalReview articlepeer-review

115 Scopus citations


Neovascularization is involved in normal development and wound repair as well as ischemic heart disease and peripheral artery disease. Both angiogenesis and vasculogenesis [de novo new vessel formation through mobilization of stem/progenitor cells from bone marrow (BM) and their homing to the ischemic sites] contribute to the formation of new blood vessels after tissue ischemia. Angiogenesis is dependent on cell proliferation, migration, and capillary tube formation in endothelial cells (ECs). Stem/progenitor cells have been used for cell-based therapy to promote revascularization after peripheral or myocardial ischemia. Excess amounts of reactive oxygen species (ROS) are involved in senescence and apoptosis of ECs and stem/progenitor cells, causing defective neovascularization. ROS at low levels function as signaling molecules to mediate cell proliferation, migration, differentiation, and gene expression. NADPH oxidase is one of the major sources of ROS in ECs and stem/progenitor cells, and is activated by various growth factors, cytokines, hypoxia, and ischemia. ROS derived from NADPH oxidase play an important role in redox signaling linked to angiogenesis ECs, as well as stem/progenitor cell mobilization, homing, and differentiation, thereby promoting neovascularization. Understanding these mechanisms may provide insight into NADPH oxidase and its mediators as potential therapeutic targets for ischemic heart and limb disease. Antioxid. Redox Signal. 11, 2517-2533.

Original languageEnglish (US)
Pages (from-to)2517-2533
Number of pages17
JournalAntioxidants and Redox Signaling
Issue number10
StatePublished - Oct 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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