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

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Serval ID
serval:BIB_E36D61042E0B
Type
Article: article from journal or magazin.
Collection
Publications
Title
Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism.
Journal
PloS One
Author(s)
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.A., Imhof B.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2011
Volume
6
Number
2
Pages
e14665
Language
english
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, Angiogenesis Inhibitors/therapeutic use, Animals, Cells, Cultured, Endothelial Cells/drug effects, Endothelial Cells/metabolism, Female, Gene Knockdown Techniques, Gene Targeting, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Biological, Molecular Targeted Therapy, NADH, NADPH Oxidoreductases/antagonists & inhibitors, NADH, NADPH Oxidoreductases/genetics, Neoplasms/blood supply, Neoplasms/drug therapy, Neovascularization, Pathologic/drug therapy, Neovascularization, Pathologic/genetics, PPAR alpha/genetics, PPAR alpha/physiology, Pyrazoles/pharmacology, Pyrazoles/therapeutic use, Pyridones/pharmacology, Pyridones/therapeutic use, RNA, Small Interfering/pharmacology, Signal Transduction/drug effects, Signal Transduction/genetics
Pubmed
Web of science
Open Access
Yes
Create date
22/03/2011 16:28
Last modification date
20/08/2019 17:07
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