title: Nox1 in cardiovascular diseases: regulation and pathophysiology.
abstract: Since its discovery in 1999, a number of studies have evaluated the role of Nox1 NADPH oxidase in the cardiovascular system. Nox1 is activated in vascular cells in response to several different agonists, with its activity regulated at the transcriptional level as well as by NADPH oxidase complex formation, protein stabilization and post-translational modification. Nox1 has been shown to decrease the bioavailability of nitric oxide, transactivate the epidermal growth factor receptor, induce pro-inflammatory signalling, and promote cell migration and proliferation. Enhanced expression and activity of Nox1 under pathologic conditions results in excessive production of reactive oxygen species and dysregulated cellular function. Indeed, studies using genetic models of Nox1 deficiency or overexpression have revealed roles for Nox1 in the pathogenesis of cardiovascular diseases ranging from atherosclerosis to hypertension, restenosis and ischaemia/reperfusion injury. These data suggest that Nox1 is a potential therapeutic target for vascular disease, and drug development efforts are ongoing to identify a specific bioavailable inhibitor of Nox1.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Gimenez
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Schickling
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Lucia R
authors.initials: LR
authors.lastname: Lopes
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, U.S.A. Veterans Affairs Medical Center of Iowa City, Iowa City, IA 52246, U.S.A. francis-miller@uiowa.edu.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human
keywords: NADPH oxidase; cell signalling; oxidative stress; reactive oxygen species; vascular disease