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dc.creatorIbarrola Ulzurrun, Jaime Franciscoes_ES
dc.creatorSádaba Sagredo, Rafaeles_ES
dc.creatorMartínez Martínez, Ernestoes_ES
dc.creatorGarcía Peña, Amaiaes_ES
dc.creatorGaínza Calleja, Aliciaes_ES
dc.date.accessioned2020-11-12T13:59:55Z
dc.date.available2020-11-12T13:59:55Z
dc.date.issued2018
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/2454/38628
dc.description.abstractAldosterone (Aldo) contributes to mitochondrial dysfunction and cardiac oxidative stress. Using a proteomic approach, A-kinase anchor protein (AKAP)-12 has been identified as a down-regulated protein by Aldo in human cardiac fibroblasts. We aim to characterize whether AKAP-12 down-regulation could be a deleterious mechanism which induces mitochondrial dysfunction and oxidative stress in cardiac cells. Aldo down-regulated AKAP-12 via its mineralocorticoid receptor, increased oxidative stress and induced mitochondrial dysfunction characterized by decreased mitochondrial-DNA and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expressions in human cardiac fibroblasts. CRISPR/Cas9-mediated knock-down of AKAP-12 produced similar deleterious effects in human cardiac fibroblasts. CRISPR/Cas9-mediated activation of AKAP-12 blunted Aldo effects on mitochondrial dysfunction and oxidative stress in human cardiac fibroblasts. In Aldo-salt-treated rats, cardiac AKAP-12, mitochondrial-DNA and PGC-1α expressions were decreased and paralleled increased oxidative stress. In myocardial biopsies from patients with aortic stenosis (AS, n = 26), AKAP-12, mitochondrial-DNA and PGC-1α expressions were decreased as compared to Controls (n = 13). Circulating Aldo levels inversely correlated with cardiac AKAP-12. PGC-1α positively associated with AKAP-12 and with mitochondrial-DNA. Aldo decreased AKAP-12 expression, impairing mitochondrial biogenesis and increasing cardiac oxidative stress. AKAP-12 down-regulation triggered by Aldo may represent an important event in the development of mitochondrial dysfunction and cardiac oxidative stress.en
dc.description.sponsorshipThis work was supported by: Miguel Servet contract CP13/00221 from the 'Instituto de Salud Carlos III-FEDER', Fondo de Investigaciones Sanitarias [PI15/02160], FIBROTARGETS project (FP7 #602904), ANR-MR focus (15-CE14-0032), Plan Estatal I+D+I 2013-2016 and Ministry of Economy and Competitiveness (SAF2016-79151-R). The Proteomics Unit of Navarrabiomed is a member of Proteored, PRB2-ISCIII, and is supported by grant PT13/0001, of the PE I+D+I 2013–2016 funded by ISCIII and FEDER.en
dc.format.extent11 p.
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherSpringeren
dc.relation.ispartofScientific Reports, 2018, 8, 6801en
dc.rights© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHeart failureen
dc.subjectMechanisms of diseaseen
dc.titleAldosterone impairs mitochondrial function in human cardiac fibroblasts via A-kinase anchor protein 12en
dc.typeinfo:eu-repo/semantics/articleen
dc.typeArtículo / Artikuluaes
dc.contributor.departmentUniversidad Pública de Navarra. Departamento de Ciencias de la Saludes_ES
dc.contributor.departmentNafarroako Unibertsitate Publikoa. Osasun Zientziak Sailaeu
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.identifier.doi10.1038/s41598-018-25068-6
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/1PE/SAF2016-79151-Ren
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/602904en
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-018-25068-6
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.type.versionVersión publicada / Argitaratu den bertsioaes


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© The Author(s) 2018.  This article is licensed under a Creative Commons Attribution 4.0 International
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder.
Except where otherwise noted, this item's license is described as © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.