Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretin

A proteomic approach was used to characterize potential mediators involved in the improvement in cardiac fibrosis observed with the administration of the mitochondrial antioxidant MitoQ in obese rats. Male Wistar rats were fed a standard diet (3.5% fat; CT) or a high-fat diet (35% fat; HFD) and trea...

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Autores: Martínez-Martínez, Ernesto, Fernández-Irigoyen, Joaquín, Santamaría, Enrique, Nieto, María Luisa, Bravo-San-Pedro, José Manuel, Cachofeiro, Victoria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/288716
Acceso en línea:http://hdl.handle.net/10261/288716
Access Level:acceso abierto
Palabra clave:Endoplasmic reticulum stress
Fibrosis
Mitochondrial oxidative stress
Obesity
Transthyretin
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spelling Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretinMartínez-Martínez, ErnestoFernández-Irigoyen, JoaquínSantamaría, EnriqueNieto, María LuisaBravo-San-Pedro, José ManuelCachofeiro, VictoriaEndoplasmic reticulum stressFibrosisMitochondrial oxidative stressObesityTransthyretinA proteomic approach was used to characterize potential mediators involved in the improvement in cardiac fibrosis observed with the administration of the mitochondrial antioxidant MitoQ in obese rats. Male Wistar rats were fed a standard diet (3.5% fat; CT) or a high-fat diet (35% fat; HFD) and treated with vehicle or MitoQ (200 μM) in drinking water for 7 weeks. Obesity modulated the expression of 33 proteins as compared with controls of the more than 1000 proteins identified. These include proteins related to endoplasmic reticulum (ER) stress and oxidative stress. Proteomic analyses revealed that HFD animals presented with an increase in cardiac transthyretin (TTR) protein levels, an effect that was prevented by MitoQ treatment in obese animals. This was confirmed by plasma levels, which were associated with those of cardiac levels of both binding immunoglobulin protein (BiP), a marker of ER stress, and fibrosis. TTR stimulated collagen I production and BiP in cardiac fibroblasts. This upregulation was prevented by the presence of MitoQ. In summary, the results suggest a role of TTR in cardiac fibrosis development associated with obesity and the beneficial effects of treatment with mitochondrial antioxidants.This research was funded by Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (FEDER) (PI18/00257, PI21/00431, CIBERCV, Madrid, Spain).Multidisciplinary Digital Publishing InstituteInstituto de Salud Carlos IIIEuropean CommissionCentro de Investigación Biomédica en Red Enfermedades Cardiovaculares (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10261/288716reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3390/ijms23158080Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2887162026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretin
title Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretin
spellingShingle Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretin
Martínez-Martínez, Ernesto
Endoplasmic reticulum stress
Fibrosis
Mitochondrial oxidative stress
Obesity
Transthyretin
title_short Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretin
title_full Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretin
title_fullStr Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretin
title_full_unstemmed Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretin
title_sort Mitochondrial oxidative stress induces cardiac fibrosis in obese rats through modulation of transthyretin
dc.creator.none.fl_str_mv Martínez-Martínez, Ernesto
Fernández-Irigoyen, Joaquín
Santamaría, Enrique
Nieto, María Luisa
Bravo-San-Pedro, José Manuel
Cachofeiro, Victoria
author Martínez-Martínez, Ernesto
author_facet Martínez-Martínez, Ernesto
Fernández-Irigoyen, Joaquín
Santamaría, Enrique
Nieto, María Luisa
Bravo-San-Pedro, José Manuel
Cachofeiro, Victoria
author_role author
author2 Fernández-Irigoyen, Joaquín
Santamaría, Enrique
Nieto, María Luisa
Bravo-San-Pedro, José Manuel
Cachofeiro, Victoria
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
European Commission
Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Endoplasmic reticulum stress
Fibrosis
Mitochondrial oxidative stress
Obesity
Transthyretin
topic Endoplasmic reticulum stress
Fibrosis
Mitochondrial oxidative stress
Obesity
Transthyretin
description A proteomic approach was used to characterize potential mediators involved in the improvement in cardiac fibrosis observed with the administration of the mitochondrial antioxidant MitoQ in obese rats. Male Wistar rats were fed a standard diet (3.5% fat; CT) or a high-fat diet (35% fat; HFD) and treated with vehicle or MitoQ (200 μM) in drinking water for 7 weeks. Obesity modulated the expression of 33 proteins as compared with controls of the more than 1000 proteins identified. These include proteins related to endoplasmic reticulum (ER) stress and oxidative stress. Proteomic analyses revealed that HFD animals presented with an increase in cardiac transthyretin (TTR) protein levels, an effect that was prevented by MitoQ treatment in obese animals. This was confirmed by plasma levels, which were associated with those of cardiac levels of both binding immunoglobulin protein (BiP), a marker of ER stress, and fibrosis. TTR stimulated collagen I production and BiP in cardiac fibroblasts. This upregulation was prevented by the presence of MitoQ. In summary, the results suggest a role of TTR in cardiac fibrosis development associated with obesity and the beneficial effects of treatment with mitochondrial antioxidants.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
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/10261/288716
url http://hdl.handle.net/10261/288716
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3390/ijms23158080
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
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
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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