Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome

Campuzano Uceda, María Victoria; Segura Puimedon, Maria, 1985-; Terrado, Verena; Sánchez Rodríguez, Carolina; Coustets, Mathilde; Menacho Márquez, Mauricio; Nevado, Julián; Francke, Uta; Pérez Jurado, Luis Alberto

Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome

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dc.contributor.author Campuzano Uceda, María Victoriaca
dc.contributor.author Segura Puimedon, Maria, 1985-ca
dc.contributor.author Terrado, Verenaca
dc.contributor.author Sánchez Rodríguez, Carolinaca
dc.contributor.author Coustets, Mathildeca
dc.contributor.author Menacho Márquez, Mauricioca
dc.contributor.author Nevado, Juliánca
dc.contributor.author Francke, Utaca
dc.contributor.author Pérez Jurado, Luis Albertoca
dc.date.accessioned 2015-04-20T07:05:15Z
dc.date.available 2015-04-20T07:05:15Z
dc.date.issued 2012ca
dc.description.abstract A hallmark feature of Williams-Beuren Syndrome (WBS) is a generalized arteriopathy due to elastin deficiency, presenting as stenoses of medium and large arteries and leading to hypertension and other cardiovascular complications. Deletion of a functional NCF1 gene copy has been shown to protect a proportion of WBS patients against hypertension, likely through reduced NADPH-oxidase (NOX)–mediated oxidative stress. DD mice, carrying a 0.67 Mb heterozygous deletion including the Eln gene, presented with a generalized arteriopathy, hypertension, and cardiac hypertrophy, associated with elevated angiotensin II (angII), oxidative stress parameters, and Ncf1 expression. Genetic (by crossing with Ncf1 mutant) and/or pharmacological (with ang II type 1 receptor blocker, losartan, or NOX inhibitor apocynin) reduction of NOX activity controlled hormonal and biochemical parameters in DD mice, resulting in normalized blood pressure and improved cardiovascular histology. We provide strong evidence for implication of the redox system in the pathophysiology of the cardiovascular disease in a mouse model of WBS. The phenotype of these mice can be ameliorated by either genetic or pharmacological intervention reducing NOX activity, likely through reduced angII–mediated oxidative stress. Therefore, anti-NOX therapy merits evaluation to prevent the potentially serious cardiovascular complications of WBS, as well as in other cardiovascular disorders mediated by similar pathogenic mechanism.en
dc.description.sponsorship This work was supported by grants from the Spanish Ministry of Science and Innovation of Health (FIS 07/0059 to VC, FIS 10/2512 to LAP-J, RD06/0020/0001 to XRB) and the VI Framework Programme of the European Union (LSHG-CT-2006-037627 to LAP-J). VC is a Miguel Servet FIS Investigator (CP04/00068). MS-P is supported by a CIBERER Fellowship. MM-M is supported by the CSIC JAE-Doc program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripten
dc.format.mimetype application/pdfca
dc.identifier.citation Campuzano V, Segura-Puimedon M, Terrado V, Sanchez-Rodriguez C, Coustets M, Menacho-Marquez M et al. Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome. PLoS Genetics. 2012;8(2):e1002458. DOI: 10.1371/journal.pgen.1002458ca
dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1002458
dc.identifier.issn 1553-7390ca
dc.identifier.uri http://hdl.handle.net/10230/23439
dc.language.iso engca
dc.publisher Public Library of Science (PLoS)ca
dc.relation.ispartof PLoS Genetics. 2012;8(2):e1002458
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/37627ca
dc.rights © 2012 Campuzano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other Williams, Síndrome deca
dc.subject.other Inhibidors enzimàticsca
dc.subject.other Pressió sanguíniaca
dc.title Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndromeen
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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