Show simple item record

Authordc.contributor.authorRomero, Alejandra
Authordc.contributor.authorDongil, Pilar
Authordc.contributor.authorValencia, Inés
Authordc.contributor.authorVallejo, Susana
Authordc.contributor.authorSan Hipólito Luengo, Álvaro
Authordc.contributor.authorDíaz Araya, Guillermo
Authordc.contributor.authorBartha, José L.
Authordc.contributor.authorGonzález Arlanzón, María M.
Authordc.contributor.authorRivilla, Fernando
Authordc.contributor.authorCuesta, Fernando de la
Authordc.contributor.authorSánchez Ferrer, Carlos
Authordc.contributor.authorPeiró, Concepción
Admission datedc.date.accessioned2022-07-15T14:11:07Z
Available datedc.date.available2022-07-15T14:11:07Z
Publication datedc.date.issued2022
Cita de ítemdc.identifier.citationAging and Disease (2022) 13:284-297es_ES
Identifierdc.identifier.other10.14336/AD.2021.0617
Identifierdc.identifier.urihttps://repositorio.uchile.cl/handle/2250/186749
Abstractdc.description.abstractThe clinical relevance of IL-1 beta in chronic inflammation underlying atherosclerosis has been reinforced by recent evidence associating pharmacological inhibition of the cytokine with lower cardiovascular risk. Previously, we have demonstrated a direct involvement of IL-1 beta in endothelial senescence. Therefore, this can be a key mechanism contributing to the sterile inflammatory milieu associated with aging, termed inflammaging. In the present study, we have evaluated whether a positive feedback of IL-1 beta in the NLRP3 inflammasome via NF-kappa B could promote human endothelial senescence in vitro and murine endothelial dysfunction in vivo. Our results indicate that the NLRP3 inflammasome is pivotal in mediating the detrimental effects of IL-1 beta, showing that auto-activation is a crucial feature boosting endothelial cell senescence in vitro, which is paralleled by vascular dysfunction in vivo. Hence, the inhibitor of NLRP3 inflammasome assembly, MCC 950, was able to disrupt the aforementioned positive loop, thus alleviating inflammation, cell senescence and vascular dysfunction. Besides, we explored alternative NLRP3 inflammasome inhibitory agents such as the RAS heptapeptide Ang-(1-7) and the anti-aging protein klotho, both of which demonstrated protective effects in vitro and in vivo. Altogether, our results highlight a fundamental role for the hereby described NLRP3 inflammasome/IL-1 beta positive feedback loop in stress-induced inflammaging and the associated vascular dysfunction, additionally providing evidence of a potential therapeutic use of MCC 950, Ang-(1-7) and recombinant klotho to block this loop and its deleterious effects.es_ES
Patrocinadordc.description.sponsorshipComunidad de Madrid 2019-T1/IND-13794 PEJ-2018-AI/SAL-9955 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1130300 European Social Fund (ESF) FPU-MECD fellowship FPU16/02612es_ES
Lenguagedc.language.isoenes_ES
Publisherdc.publisherInternational Society on Aging and Diseasees_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
Sourcedc.sourceAging and Diseasees_ES
Keywordsdc.subjectInterleukin-1 betaes_ES
Keywordsdc.subjectNLRP3 inflammasomees_ES
Keywordsdc.subjectEndothelial celles_ES
Keywordsdc.subjectSenescencees_ES
Keywordsdc.subjectVascular dysfunctiones_ES
Keywordsdc.subjectAngiotensin-(1-7)es_ES
Keywordsdc.subjectKlothoes_ES
Títulodc.titlePharmacological blockade of NLRP3 inflammasome/IL1β-positive loop mitigates endothelial cell senescence and dysfunctiones_ES
Document typedc.typeArtículo de revistaes_ES
dc.description.versiondc.description.versionVersión publicada - versión final del editores_ES
dcterms.accessRightsdcterms.accessRightsAcceso abiertoes_ES
Catalogueruchile.catalogadorapces_ES
Indexationuchile.indexArtículo de publícación WoSes_ES


Files in this item

Icon

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivs 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States