Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms

This article belongs to the Special Issue Molecular and Cellular Mechanisms of Marfan Syndrome.

Detalles Bibliográficos
Autores: Marcos-Ríos, Daniel, Rochano-Ortiz, Antonio, Méndez-Barbero, Nerea, Oller, Jorge
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/391306
Acceso en línea:http://hdl.handle.net/10261/391306
Access Level:acceso abierto
Palabra clave:Mitochondria
Aneurysm
Marfan syndrome
Loeys-Dietz syndrome
Familial thoracic aortic aneurysm
Nicotinamide riboside
Vascular smith muscle cells
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spelling Defective Mitochondrial Respiration in Hereditary Thoracic AneurysmsMarcos-Ríos, DanielRochano-Ortiz, AntonioMéndez-Barbero, NereaOller, JorgeMitochondriaAneurysmMarfan syndromeLoeys-Dietz syndromeFamilial thoracic aortic aneurysmNicotinamide ribosideVascular smith muscle cellsThis article belongs to the Special Issue Molecular and Cellular Mechanisms of Marfan Syndrome.Thoracic aortic aneurysms are life-threatening vascular conditions linked to inherited disorders such as Marfan syndrome, Loeys–Dietz syndrome, vascular Ehlers–Danlos syndrome, and familial thoracic aortic aneurysms and dissections. While traditionally associated with the extracellular matrix and contractile defects in vascular smooth muscle cells, emerging evidence suggests the key role of mitochondrial dysfunction. Here, we show that the overexpression of ACTA2R179H and TGFBR2G357W in murine aortic VSMCs reduces Mitochondrial Transcription Factor A (Tfam) expression, decreases mitochondrial DNA (mtDNA) content, and impairs oxidative phosphorylation, shifting metabolism toward glycolysis. Notably, nicotinamide riboside, a NAD+ precursor, restores mitochondrial respiration, increases Tfam and mtDNA levels, and promotes a contractile phenotype by enhancing actin polymerization and reducing matrix metalloproteinase activity. These findings identify mitochondrial dysfunction as a shared feature in hereditary thoracic aortic aneurysm, not only in Marfan syndrome, but also in other genetic forms, and highlight mitochondrial boosters as a potential therapeutic strategy.A.R.-O. is supported by the Conchita-Rábago Foundation 2024 grant. N.M.-B. is supported by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (ISCiii/FEDER, PI21/01126 and PI24/00180, CP19/00151 Miguel Servet contract), Sociedad Española de Arteriosclerosis, and CIBERCV, Spain. J.O. is supported by a Ramón y Cajal contract (RYC2021-033343-I), and grant from Spanish Science Ministry (PID2022-137730OA-I00/ AEI/10.13039/501100011033/ FEDER, UE) and Marfan Spanish association (SIMA, www.Marfan.es).Peer reviewedMultidisciplinary Digital Publishing InstituteFundación Conchita Rábago de Jiménez DíazInstituto de Salud Carlos IIISociedad Española de ArteriosclerosisCentro de Investigación Biomédica en Red Enfermedades Cardiovaculares (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionThe Marfan FoundationRochano-Ortiz, Antonio [0009-0006-1456-2946]Oller, Jorge [0000-0002-2224-2954]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/391306reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F01126info:eu-repo/grantAgreement/ISCIII//PI24info:eu-repo/grantAgreement/ISCIII//CP19info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-137730OA-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/cells14110768https://doi.org/10.3390/cells14110768Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3913062026-05-22T06:33:51Z
dc.title.none.fl_str_mv Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms
title Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms
spellingShingle Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms
Marcos-Ríos, Daniel
Mitochondria
Aneurysm
Marfan syndrome
Loeys-Dietz syndrome
Familial thoracic aortic aneurysm
Nicotinamide riboside
Vascular smith muscle cells
title_short Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms
title_full Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms
title_fullStr Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms
title_full_unstemmed Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms
title_sort Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms
dc.creator.none.fl_str_mv Marcos-Ríos, Daniel
Rochano-Ortiz, Antonio
Méndez-Barbero, Nerea
Oller, Jorge
author Marcos-Ríos, Daniel
author_facet Marcos-Ríos, Daniel
Rochano-Ortiz, Antonio
Méndez-Barbero, Nerea
Oller, Jorge
author_role author
author2 Rochano-Ortiz, Antonio
Méndez-Barbero, Nerea
Oller, Jorge
author2_role author
author
author
dc.contributor.none.fl_str_mv Fundación Conchita Rábago de Jiménez Díaz
Instituto de Salud Carlos III
Sociedad Española de Arteriosclerosis
Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (España)
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
European Commission
The Marfan Foundation
Rochano-Ortiz, Antonio [0009-0006-1456-2946]
Oller, Jorge [0000-0002-2224-2954]
dc.subject.none.fl_str_mv Mitochondria
Aneurysm
Marfan syndrome
Loeys-Dietz syndrome
Familial thoracic aortic aneurysm
Nicotinamide riboside
Vascular smith muscle cells
topic Mitochondria
Aneurysm
Marfan syndrome
Loeys-Dietz syndrome
Familial thoracic aortic aneurysm
Nicotinamide riboside
Vascular smith muscle cells
description This article belongs to the Special Issue Molecular and Cellular Mechanisms of Marfan Syndrome.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/391306
url http://hdl.handle.net/10261/391306
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F01126
info:eu-repo/grantAgreement/ISCIII//PI24
info:eu-repo/grantAgreement/ISCIII//CP19
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-137730OA-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/cells14110768
https://doi.org/10.3390/cells14110768
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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