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Cardiovascular Disorders

Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARa Mediated Mechanism
Published: Monday, February 07, 2011
Author: Sarah Garrido-Urbani et al.

by Sarah Garrido-Urbani, Stephane Jemelin, Christine Deffert, Stéphanie Carnesecchi, Olivier Basset, Cédric Szyndralewiez, Freddy Heitz, Patrick Page, Xavier Montet, Liliane Michalik, Jack Arbiser, Curzio Rüegg, Karl Heinz Krause, Beat Imhof

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 PPARa, a regulator of NF-?B. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARa dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies.