دورية أكاديمية
Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells
| العنوان: | Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells |
|---|---|
| المؤلفون: | Benedicto, Ignacio, Carmona, Rosa María, Barettino, Ana, Espinós-Estévez, Carla, Gonzalo, Pilar, Nevado, Rosa M., De la Fuente Pérez, Miguel, Andrés-Manzano, María J., González-Gómez, Cristina, Rolas, Löic, Dorado, Beatriz, Nourshargh, Sussan, Hamczyk, Magda R., Andrés, Vicente |
| المساهمون: | Ministerio de Ciencia e Innovación (España), Comunidad de Madrid, European Commision, Fundación la Caixa, Ministerio de Educación, Cultura y Deporte (España), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Pro-CNIC Foundation, Benedicto, Ignacio, Carmona, Rosa María, Barettino, Ana, Espinós-Estévez, Carla, Gonzalo, Pilar, Nevado, Rosa M., De la Fuente Pérez, Miguel, Andrés-Manzano, María J., Rolas, Löic, Dorado, Beatriz, Nourshargh, Sussan, Hamczyk, Magda R., Andrés, Vicente |
| بيانات النشر: | National Academy of Sciences (U.S.) |
| سنة النشر: | 2024 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Hutchinson–Gilford progeria syndrome, Atherosclerosis, Endothelial cells, Vascular smooth muscle cells |
| الوصف: | 3 p.-2 fig. ; 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. ; 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0027-8424 1091-6490 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-141211OB-I00/ES/SINDROME DE PROGERIA DE HUTCHINSON-GILFORD: NUEVOS PARADIGMAS MECANISTICOS Y DESARROLLO DE TERAPIAS INNOVADORAS EN MODELOS PRECLINICOS/; 2017- T1/BMD- 5247; 2021- 5A/BMD- 20944; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-137111OA-I00/ES/CONDICIONAMIENTO VASOPROTECTOR PARA MEJORAR LA MECANOTRANSDUCCION ENDOTELIAL EN TEJIDOS ENVEJECIDOS: IMPLICACIONES EN REGENERACION HEPATICA/; Publisher's version; https://doi.org/10.1073/pnas.2400752121Test; Sí; Proceedings of the National Academy of Sciences of the USA 121(18) e2400752121 (2024); http://hdl.handle.net/10261/356114Test |
| DOI: | 10.1073/pnas.2400752121 |
| الإتاحة: | https://doi.org/10.1073/pnas.2400752121Test http://hdl.handle.net/10261/356114Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.A7D381B3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00278424 10916490 |
|---|---|
| DOI: | 10.1073/pnas.2400752121 |