dc.contributor.author | Benedicto, Ignacio | |
dc.contributor.author | Carmona, Rosa M | |
dc.contributor.author | Barettino, Ana | |
dc.contributor.author | Espinós-Estévez, Carla | |
dc.contributor.author | Gonzalo, Pilar | |
dc.contributor.author | Nevado, Rosa M | |
dc.contributor.author | de la Fuente-Pérez, Miguel | |
dc.contributor.author | Andres-Manzano, Maria J. | |
dc.contributor.author | Gonzalez-Gomez, Cristina | |
dc.contributor.author | Rolas, Loïc | |
dc.contributor.author | Dorado, Beatriz | |
dc.contributor.author | Nourshargh, Sussan | |
dc.contributor.author | Hamczyk, Magda R. | |
dc.contributor.author | Andres, Vicente | |
dc.date.accessioned | 2024-04-24T15:39:00Z | |
dc.date.available | 2024-04-24T15:39:00Z | |
dc.date.issued | 2024-04-30 | |
dc.identifier.citation | Proc Natl Acad Sci USA. 2024 Apr 30;121(18):e2400752121. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19193 | |
dc.description.abstract | Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by the expression of progerin, a mutant protein that accelerates aging and precipitates death. Given that atherosclerosis complications are the main cause of death in progeria, here, we investigated whether progerin-induced atherosclerosis is prevented in HGPSrev-Cdh5-CreERT2 and HGPSrev-SM22α-Cre mice with progerin suppression in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), respectively. HGPSrev-Cdh5-CreERT2 mice were undistinguishable from HGPSrev mice with ubiquitous progerin expression, in contrast with the ameliorated progeroid phenotype of HGPSrev-SM22α-Cre mice. To study atherosclerosis, we generated atheroprone mouse models by overexpressing a PCSK9 gain-of-function mutant. While HGPSrev-Cdh5-CreERT2 and HGPSrev mice developed a similar level of excessive atherosclerosis, plaque development in HGPSrev-SM22α-Cre mice was reduced to wild-type levels. Our studies demonstrate that progerin suppression in VSMCs, but not in ECs, prevents exacerbated atherosclerosis in progeroid mice. | es_ES |
dc.description.sponsorship | We thank R.H. Adams for Tg(Cdh5-cre/ERT2)1Rha mice, J.F.
Bentzon for rAAV8-mPCSK9D377Y, and S. Bartlett for English editing. Aorta and mouse
icons were made with BioRender.com licensed to V.A. Work supported by grant
PID2022-141211OB-I00 funded by MICIU/AEI/10.13039/501100011033 and ERDF/
EU. I.B. was supported by Comunidad de Madrid (2017-T1/BMD-5247 and 2021-5A/
BMD-20944) with cofunding from European Structural and Investment Fund, RYC2021-
033805-I (MICIU/AEI/10.13039/501100011033, European Union NextGenerationEU/
PRTR), and PID2022-137111OA-I00 (MICIU/AEI/10.13039/501100011033, ERDF/EU).
Salary support to A.B. (BES-2017-079705, MICIU/AEI/10.13039/501100011033,
ESF), C.E.-E. (Fundación “la Caixa”, LCF/BQ/DR19/1170012), R.M.N (Ministerio
de Educación, Cultura y Deporte, FPU16/05027), and M.R.H. (MICIU, IJC2019-
040798-I). CNIC is supported by Instituto de Salud Carlos III (ISCIII), Ministerio
de Ciencia, Innovación y Universidades (MICIU), Pro-CNIC Foundation and is a
Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIU/
AEI/10.13039/501100011033). Generation of anti-progerin antibody funded by
Wellcome Trust (098291/Z/12/Z, 221699/Z/20/Z). Microscopy and Dynamic Imaging
Unit-CNIC/ICTS-ReDib supported by ICTS-2018-04-CNIC-16 funded by MICIU/
AEI/10.13039/501100011033 and ERDF–A way to make Europe. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | National Academy of Sciences | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 38648484 | es_ES |
dc.format.volume | 121 | es_ES |
dc.format.number | 18 | es_ES |
dc.format.page | e2400752121 | es_ES |
dc.identifier.doi | 10.1073/pnas.2400752121 | es_ES |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1091-6490 | es_ES |
dc.relation.publisherversion | 10.1073/pnas.2400752121 | es_ES |
dc.identifier.journal | Proceedings of the National Academy of Sciences of the United States of America | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genética | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2022-141211OB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/MICIU/AEI/10.13039/501100011033 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/2017-T1/BMD-5247 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/2021-5A/BMD-20944 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2022-137111OA-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/LCF/BQ/DR19/1170012 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IJC2019-040798-I | es_ES |