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Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism

Deffert, Christine
Szyndralewiez, Cédric
Page, Patrick
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Published in PLOS ONE. 2011, vol. 6, no. 2, e14665
Abstract 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.
Keywords Angiogenesis Inhibitors/pharmacology/therapeutic useAnimalsCells, CulturedEndothelial Cells/drug effects/metabolismFemaleGene Knockdown TechniquesGene TargetingHumansMiceMice, Inbred C57BLMice, KnockoutModels, BiologicalMolecular Targeted TherapyNADH, NADPH Oxidoreductases/antagonists & inhibitors/genetics/physiologyNeoplasms/blood supply/drug therapy/geneticsNeovascularization, Pathologic/drug therapy/geneticsPPAR alpha/genetics/physiologyPyrazoles/pharmacology/therapeutic usePyridones/pharmacology/therapeutic useRNA, Small Interfering/pharmacologySignal Transduction/drug effects/genetics
PMID: 21326871
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Article (Published version) (671 Kb) - public document Free access
Research groups Molécules d'adhésion et processus de migration cellulaire (167)
Radicaux libres et cellules souches embryonnaires (60)
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GARRIDO-URBANI, Sarah et al. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism. In: PLOS ONE, 2011, vol. 6, n° 2, p. e14665. doi: 10.1371/journal.pone.0014665 https://archive-ouverte.unige.ch/unige:25344

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Deposited on : 2013-01-10

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