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Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARα Mediated Mechanism

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...

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Detalles Bibliográficos
Autores principales: Garrido-Urbani, Sarah, Jemelin, Stephane, Deffert, Christine, Carnesecchi, Stéphanie, Basset, Olivier, Szyndralewiez, Cédric, Heitz, Freddy, Page, Patrick, Montet, Xavier, Michalik, Liliane, Arbiser, Jack, Rüegg, Curzio, Krause, Karl Heinz, Imhof, Beat
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034713/
https://www.ncbi.nlm.nih.gov/pubmed/21326871
http://dx.doi.org/10.1371/journal.pone.0014665
Descripción
Sumario: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.