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dc.contributor.author | Santamans, Ayelén M | |
dc.contributor.author | Cicuéndez, Beatriz | |
dc.contributor.author | Mora, Alfonso | |
dc.contributor.author | Villalba-Orero, María | |
dc.contributor.author | Rajlic, Sanela | |
dc.contributor.author | Crespo, María | |
dc.contributor.author | Vo, Paula | |
dc.contributor.author | Jerome, Madison | |
dc.contributor.author | Macías, Álvaro | |
dc.contributor.author | López, Juan Antonio | |
dc.contributor.author | Leiva, Magdalena | |
dc.contributor.author | Rocha, Susana F | |
dc.contributor.author | León, Marta | |
dc.contributor.author | Rodríguez, Elena | |
dc.contributor.author | Leiva, Luis | |
dc.contributor.author | Pintor Chocano, Aránzazu | |
dc.contributor.author | García Lunar, Inés | |
dc.contributor.author | García-Álvarez, Ana | |
dc.contributor.author | Hernansanz-Agustín, Pablo | |
dc.contributor.author | Peinado, Víctor I | |
dc.contributor.author | Barberá, Joan Albert | |
dc.contributor.author | Ibáñez, Borja | |
dc.contributor.author | Vázquez, Jesús | |
dc.contributor.author | Spinelli, Jessica B | |
dc.contributor.author | Daiber, Andreas | |
dc.contributor.author | Oliver, Eduardo | |
dc.contributor.author | Sabio, Guadalupe | |
dc.date.accessioned | 2024-03-11T14:46:13Z | |
dc.date.available | 2024-03-11T14:46:13Z | |
dc.date.issued | 2024-01-19 | |
dc.identifier.citation | Sci Adv. 2024 Jan 19;10(3):eadk6524. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/18917 | |
dc.description.abstract | Pulmonary hypertension (PH) can affect both pulmonary arterial tree and cardiac function, often leading to right heart failure and death. Despite the urgency, the lack of understanding has limited the development of effective cardiac therapeutic strategies. Our research reveals that MCJ modulates mitochondrial response to chronic hypoxia. MCJ levels elevate under hypoxic conditions, as in lungs of patients affected by COPD, mice exposed to hypoxia, and myocardium from pigs subjected to right ventricular (RV) overload. The absence of MCJ preserves RV function, safeguarding against both cardiac and lung remodeling induced by chronic hypoxia. Cardiac-specific silencing is enough to protect against cardiac dysfunction despite the adverse pulmonary remodeling. Mechanistically, the absence of MCJ triggers a protective preconditioning state mediated by the ROS/mTOR/HIF-1α axis. As a result, it preserves RV systolic function following hypoxia exposure. These discoveries provide a potential avenue to alleviate chronic hypoxia-induced PH, highlighting MCJ as a promising target against this condition. | es_ES |
dc.description.sponsorship | This study was financially supported by the following: Interacciones celulares y sistémicas entre el cáncer y la señalización metabólica, exp: RED2022-134397-T (G.S.); Proyectos I+D+i 2019 - Proyecto MINECO-PID2019-104399RB-I00 financiado por MCIN/AEI/10.13039/501100011033 (G.S.); Proyectos de I+D de Generación de Conocimiento 2018 funded by Ministerio de Economía y Competitividad (PGC2018-097019-B-I00) (G.S.); PreMed-Exp: PMP21/00057 (G.S.); Fundación Jesús Serra (G.S.); EFSD/Lilly European Diabetes Research Programme (G.S.); BBVA Foundation Leonardo Grants program for Researchers and Cultural Creators (Investigadores-BBVA-2017) (G.S.); Fundación AECC PROYE19047SABI (G.S.); Comunidad de Madrid IMMUNOTHERCAN-CM S2010/BMD-2326 (G.S.); FPI Severo Ochoa CNIC program (BES-2016-077635) (A.M.S.); JDC-2020 Incorporación (IJC2020-042679-I) (P.H.-A.); Fondo Europeo de Desarrollo Regional (FEDER) Instituto de Salud Carlos III-Fondo de Investigación Sanitaria PI17/00995 (A.G.-Á.); Fondo Europeo de Desarrollo Regional (FEDER) Instituto de Salud Carlos III-Fondo de Investigación Sanitaria (PI20/00742) (A.G.-Á.); Intensificación AES2019 (AGA); Fundación “La Caixa”: Macromoleculopathies (LCF/PR/HR19/52160013) of the call HEALTH RESEARCH 2018 (Á.Ma.); Programa de Atracción de Talento (2017-T1/BMD-5185) funded by Comunidad de Madrid (E.O.); Ramón y Cajal grant (RYC2020-028884-I) funded by MCIN/ AEI/10.13039/501100011033 and by “ESF Investing in your future” (E.O.); Juan de la Cierva Incorporación Grant (IJCI-2016-27698) (M.V.O.); Worcester Foundation for Biomedical Research (J.B.S.); Boehringer Ingelheim Foundation (collaborative research group “Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutics”) (A.D.); Foundation Heart of Mainz (A.D.); DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany (A.D.); Ministerio de Ciencia e Innovación (PGC2018-097019-B-I00, PID2021-122348NB-I00, PLEC2022-009235, and PLEC2022-009298) (J.V.); Fundación “La Caixa” (HR17-00247 and HR22-00253) (J.V.); Carlos III Institute of Health-Fondo de Investigación Sanitaria grant PRB3 (PT17/0019/0003- ISCIII-SGEFI/ERDF, ProteoRed) (J.V.); and Comunidad de Madrid (IMMUNO-VAR, P2022/BMD-7333) (J.V.). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Association for the Advancement of Science (AAAS) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Hypertension, Pulmonary | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Hypoxia | es_ES |
dc.subject.mesh | Lung | es_ES |
dc.subject.mesh | Myocardium | es_ES |
dc.subject.mesh | Pulmonary Artery | es_ES |
dc.subject.mesh | Swine | es_ES |
dc.title | MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 38241373 | es_ES |
dc.format.volume | 10 | es_ES |
dc.format.number | 3 | es_ES |
dc.format.page | eadk6524 | es_ES |
dc.identifier.doi | 10.1126/sciadv.adk6524 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Agencia Estatal de Investigación (España) | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | es_ES |
dc.contributor.funder | Fundación BBVA | es_ES |
dc.contributor.funder | Asociación Española Contra el Cáncer | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2375-2548 | es_ES |
dc.relation.publisherversion | 10.1126/sciadv.adk6524 | es_ES |
dc.identifier.journal | Science advances | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Papel de las quinasas activadas por el estrés en el desarrollo de enfermedades cardiovasculares, diabetes y cáncer | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RED2022-134397-T | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/MINECO-PID2019-104399RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/ MCIN/AEI/10.13039/501100011033 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PGC2018-097019-BI00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PMP21/00057 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/AECC/PROYE19047SABI | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IMMUNOTHERCANCMS2010/BMD-2326 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/BES-2016-077635 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IJC2020-042679-I | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI17/00995 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI20/00742 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/LCF/PR/HR19/52160013 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/2017T1/BMD-5185 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IJCI-2016-27698 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PGC2018-097019-BI00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2021-122348NB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PLEC2022-009298 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR17-00247 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR22-00253 | es_ES |