Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARα Mediated Mechanism
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Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies.
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Knockdown of NOX1 can decrease angiogenesis.
“For instance, knockdown of NOX1 can decrease angiogenesis (343), whereas increased NOX1 promotes tumor angiogenesis and growth (582).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [343]
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- Authors
- Garrido-Urbani, S., Jemelin, S., Deffert, C., Carnesecchi, S., Basset, O., Szyndralewiez, C., Heitz, F., Page, P., Montet, X., Michalik, L., Arbiser, J., Rüegg, C., Krause, K. H., & Imhof, B.
- Affiliations
- University of Geneva (CH)
- Genkyotex (Switzerland) (CH)
- University of Lausanne (CH)
- Emory University (US)
- University of Fribourg (CH)
- Corresponding author
- Imhof, Beat
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-02-07
- Volume
- 6
- Issue
- 2
- Pages
- e14665
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3034713
- OpenAlex
- W1977185778
- Cited by
- 143
- References
- 73
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 11 · 2016: 7 · 2015: 14 · 2014: 21 · 2013: 17 · 2012: 19
- FWCI
- 8.43
- Type
- journal article
- Language
- en
- Update notices
- correction (2011-02-17)
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation (310030)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (120184, 310030)
- Université de Lausanne
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- NOX1, tumor angiogenesis, PPARα, reactive oxygen species, endothelial cells, endothelial cell migration, tube formation, NF-κB, NOX inhibitors, anti-angiogenic therapy, NOX2, NOX4
- MeSH terms
- NADPH Oxidase 1, Animals, Cells, Cultured, Female, Humans, Mice, Inbred C57BL, Models, Biological, NADH, NADPH Oxidoreductases, Neoplasms, Neovascularization, Pathologic, Pyrazoles, Pyridones, Signal Transduction, Mice, Knockout, Gene Targeting, Angiogenesis Inhibitors, RNA, Small Interfering, Endothelial Cells, PPAR alpha, Mice, Gene Knockdown Techniques, Molecular Targeted Therapy
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