dc.contributor.author | Pun-García, Andrés | |
dc.contributor.author | Clemente-Moragón, Agustín | |
dc.contributor.author | Villena-Gutierrez, Rocio | |
dc.contributor.author | Gómez, Monica | |
dc.contributor.author | Sanz-Rosa, David | |
dc.contributor.author | Díaz-Guerra, Anabel | |
dc.contributor.author | Prados, Belén | |
dc.contributor.author | Medina, Juan Pablo | |
dc.contributor.author | Montó, Fermí | |
dc.contributor.author | Ivorra, Maria Dolores | |
dc.contributor.author | Márquez-López, Cristina | |
dc.contributor.author | Cannavo, Alessandro | |
dc.contributor.author | Bernal, Juan A | |
dc.contributor.author | Koch, Walter J | |
dc.contributor.author | Fuster, Valentin | |
dc.contributor.author | de la Pompa, Jose Luis | |
dc.contributor.author | Oliver, Eduardo | |
dc.contributor.author | Ibáñez, Borja | |
dc.date.accessioned | 2022-12-15T12:32:25Z | |
dc.date.available | 2022-12-15T12:32:25Z | |
dc.date.issued | 2022-11-29 | |
dc.identifier.citation | Basic Res Cardiol. 2022 Nov 29;117(1):62 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/15275 | |
dc.description.abstract | Aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and heart failure (HF). There is a lack of therapies able to prevent/revert AS-induced HF. Beta3 adrenergic receptor (β3AR) signaling is beneficial in several forms of HF. Here, we studied the potential beneficial effect of β3AR overexpression on AS-induced HF. Selective β3AR stimulation had a positive inotropic effect. Transgenic mice constitutively overexpressing human β3AR in the heart (c-hβ3tg) were protected from the development of HF in response to induced AS, and against cardiomyocyte mitochondrial dysfunction (fragmented mitochondria with remodeled cristae and metabolic reprogramming featuring altered substrate use). Similar beneficial effects were observed in wild-type mice inoculated with adeno-associated virus (AAV9) inducing cardiac-specific overexpression of human β3AR before AS induction. Moreover, AAV9-hβ3AR injection into wild-type mice at late disease stages, when cardiac hypertrophy and metabolic reprogramming are already advanced, reversed the HF phenotype and restored balanced mitochondrial dynamics, demonstrating the potential of gene-therapy-mediated β3AR overexpression in AS. Mice with cardiac specific ablation of Yme1l (cYKO), characterized by fragmented mitochondria, showed an increased mortality upon AS challenge. AAV9-hβ3AR injection in these mice before AS induction reverted the fragmented mitochondria phenotype and rescued them from death. In conclusion, our results step out that β3AR overexpression might have translational potential as a therapeutic strategy in AS-induced HF. | es_ES |
dc.description.sponsorship | Spanish Ministry of Science and Innovation (MICINN)
RETOS2019-107332RB-I00, European Commission (ERC-CoG
grant N° 819775), ERA-CVD Joint Translational Call 2016 (funded
through the Instituto de Salud Carlos III (ISCIII) and the European
Regional Development Fund (ERDF), # AC16/00021), and BBVA
foundation grant (# BIO CAR 0265) to B.I. PID2019-104776RB-I00,
CB16/11/00399 (CIBER CV), and RD16/0011/0021 (TERCEL) from
MCIN/AEI/ https://doi.org/10.13039/501100011033and a grant from
the Fundación BBVA (Ref.: BIO14_298) to J.L.d.l.P. E.O. is recipient
of funds from Programa de Atracción de Talento (2017-T1/BMD-5185)
of Comunidad de Madrid and from a Ramón y Cajal grant (RYC2020-
028884-I) funded by MCIN/AEI/ https://doi.org/10.13039/50110
0011033 and by “ESF Investing in your future. A.P. is benefciary of
a FPI fellowship by the MCI (BES-2012–061091), R.V-G. of a Spanish National doctorate fellowship funded by ISCIII (Contratos PFIS
FI17/00045) and A.C-M. is benefciary of a FPU fellowship from the MCI (FPU2017/01932). This study was partially supported by the
Comunidad de Madrid (RENIM-CM, S2017/BMD-3867 & P2022/
BMD-7403) and cofunded with European structural and investment
funds. The CNIC is supported by the ISCIII, the MICINN and the Pro
CNIC Foundation, and is a Center of Excellence Severo Ochoa (grant
CEX2020-001041-S funded by MICIN/AEI/https://doi.org/10.13039/
501100011033). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Heart Failure | es_ES |
dc.subject.mesh | Aortic Valve Stenosis | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Receptors, Adrenergic, beta-3 | es_ES |
dc.subject.mesh | Mitochondrial Dynamics | es_ES |
dc.subject.mesh | Hypertrophy, Left Ventricular | es_ES |
dc.subject.mesh | Myocytes, Cardiac | es_ES |
dc.subject.mesh | Mice, Transgenic | es_ES |
dc.subject.mesh | Metalloendopeptidases | es_ES |
dc.title | Beta-3 adrenergic receptor overexpression reverses aortic stenosis-induced heart failure and restores balanced mitochondrial dynamics. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 36445563 | es_ES |
dc.format.volume | 117 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 62 | es_ES |
dc.identifier.doi | 10.1007/s00395-022-00966-z | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Fundación BBVA | es_ES |
dc.contributor.funder | Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares) | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | European Science Foundation | es_ES |
dc.contributor.funder | Fundación ProCNIC | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1435-1803 | es_ES |
dc.relation.publisherversion | 10.1007/s00395-022-00966-z | es_ES |
dc.identifier.journal | Basic research in cardiology | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Laboratorio Traslacional para la Imagen y Terapia Cardiovascular | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/AC16/00021 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RETOS2019-107332RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/ERC-CoG/819775 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-104776RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/CB16/11/00399 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RD16/0011/0021 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/BBVA/BIO14_298 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/2017-T1/BMD-5185 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RYC2020- 028884-I | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/BES-2012–061091 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PFIS FI17/00045 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/FPU2017/01932 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/S2017/BMD-3867 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/P2022/ BMD-7403 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/CEX2020-001041-S | es_ES |