The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation

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dc.contributor.author Romero, Alejandra
dc.contributor.author San Hipólito-Luengo, Álvaro
dc.contributor.author Villalobos, Laura A.
dc.contributor.author Vallejo, Susana
dc.contributor.author Valencia, Inés
dc.contributor.author Michalska, Patrycja
dc.contributor.author Pajuelo-Lozano, Natalia
dc.contributor.author Sánchez-Pérez, Isabel
dc.contributor.author León, Rafael
dc.contributor.author Bartha, José Luis
dc.contributor.author Sanz, María Jesús
dc.contributor.author Erusalimsky, Jorge D.
dc.contributor.author Sánchez-Ferrer, Carlos F.
dc.contributor.author Romacho, Tania
dc.contributor.author Peiró, Concepción
dc.contributor.other UAM. Departamento de Bioquímica es_ES
dc.contributor.other UAM. Departamento de Farmacología es_ES
dc.contributor.other UAM. Departamento de Obstetricia y Ginecología es_ES
dc.contributor.other Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM) es_ES
dc.date.accessioned 2019-09-16T14:51:02Z
dc.date.available 2019-09-16T14:51:02Z
dc.date.issued 2019-06-01
dc.identifier.citation Aging Cell 18.3 (2019): :e12913. en_US
dc.identifier.issn 1474-9718 (print) es_ES
dc.identifier.issn 1474-9726 (online) es_ES
dc.identifier.uri http://hdl.handle.net/10486/688597
dc.description.abstract Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin–angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence-associated galactosidase (SA-β-gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers. By activating the G protein-coupled receptor Mas, Ang-(1-7) inhibited the pro-senescence action of Ang II, but also of a non-RAS stressor such as the cytokine IL-1β. Moreover, Ang-(1-7) enhanced endothelial klotho levels, while klotho silencing resulted in the loss of the anti-senescence action of the heptapeptide. Indeed, both Ang-(1-7) and recombinant klotho activated the cytoprotective Nrf2/heme oxygenase-1 (HO-1) pathway. The HO-1 inhibitor tin protoporphyrin IX prevented the anti-senescence action evoked by Ang-(1-7) or recombinant klotho. Overall, the present study identifies Ang-(1-7) as an anti-senescence peptide displaying its protective action beyond the RAS by consecutively activating klotho and Nrf2/HO-1. Ang-(1-7) mimetic drugs may thus prove useful to prevent endothelial cell senescence and its related vascular complications. en_US
dc.description.sponsorship Plan Nacional I+D+i, Grant/Award Number: SAF2017-84776-R, SAF2017-89714-R; Fundación La Caixa, Grant/Award Number: CaixaImpulse CI17/00048; IS Carlos III, Grant/Award Number: PI17/01700 and PI17/01401 en_US
dc.format.extent 12 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Anatomical Society and John Wiley & Sons Ltd. en_US
dc.relation.ispartof Aging Cell en_US
dc.rights © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley&Sons Ltd. en_US
dc.subject.other Angiotensin-(1-7) en_US
dc.subject.other Endothelial senescence en_US
dc.subject.other Heme oxygenase-1 en_US
dc.subject.other Klotho en_US
dc.subject.other Nuclear factor (erythroid-derived 2)-like 2 en_US
dc.subject.other Vascular aging en_US
dc.title The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation en-US
dc.type article en
dc.subject.eciencia Farmacia es_ES
dc.relation.publisherversion https://doi.org/10.1111/acel.12913 es_ES
dc.identifier.doi 10.1111/acel.12913 es_ES
dc.identifier.publicationfirstpage e12913-12 es_ES
dc.identifier.publicationissue 3 es_ES
dc.identifier.publicationlastpage e12913-12 es_ES
dc.identifier.publicationvolume 18 es_ES
dc.relation.projectID Gobierno de España. SAF2017-84776-R es_ES
dc.relation.projectID Gobierno de España. SAF2017-89714-R es_ES
dc.relation.projectID Gobierno de España. PI17/01700 es_ES
dc.relation.projectID Gobierno de España. PI17/01401 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en
dc.authorUAM San Hipólito Luengo, Álvaro (278899)
dc.authorUAM Sánchez Pérez, María Isabel (261233)
dc.authorUAM León Martínez, Rafael (264118)
dc.authorUAM Bartha Rasero, José Luis (262515)
dc.authorUAM Sánchez Ferrer, Carlos Félix (259402)
dc.authorUAM Romacho Romero, Tania Del Mar (263921)
dc.authorUAM Peiró Vallejo, M. Concepción (259003)


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