Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload
Background The mitochondrial unfolded protein response (UPRmt) is activated when misfolded proteins accumulate within mitochondria and leads to increased expression of mitochondrial chaperones and proteases to maintain protein quality and mitochondrial function. Cardiac mitochondria are essential fo...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/63144 |
| Acceso en línea: | https://hdl.handle.net/10171/63144 |
| Access Level: | acceso abierto |
| Palabra clave: | Cardiomyocyte Heart Mitochondria Pressure overload Unfolded protein response |
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Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overloadSmyrnias, I. (Ioannis)|||/items/d5ab339a-af96-4b6c-a384-6588f4d711a2Gray, S.P. (Stephen P.)|||/items/33ad7431-c580-46c5-928a-0d50a219dc7eOkonko, D. (Darlington)|||/items/d79a3fa8-adcf-4905-bc75-e4fcacb383f0Sawyer, G. (Greta)|||/items/22d9a898-ace6-4a51-a94b-1d2b76ceb15dZoccarato, A. (Anna)|||/items/bdd86a00-0deb-42de-a739-a2268fd2d6c0Catibog, N. (Norman)|||/items/b2c6e5cc-a4b8-439c-919b-6b62d995c705Lopez-Salazar, M.B. (María Begoña)|||/items/153e0e37-14b0-403e-afab-8af00c4edde0Gonzalez, A. (Arantxa)|||/items/9c64c0f4-66b4-4b51-8593-0e50c091a515Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1Diez-Espino, J. (Javier)|||/items/125690ae-ba81-4d29-a748-e644f3584853Shah, A.M. (Ajay M.)|||/items/3bc739ce-1498-4741-8de7-e054feba2801CardiomyocyteHeartMitochondriaPressure overloadUnfolded protein responseBackground The mitochondrial unfolded protein response (UPRmt) is activated when misfolded proteins accumulate within mitochondria and leads to increased expression of mitochondrial chaperones and proteases to maintain protein quality and mitochondrial function. Cardiac mitochondria are essential for contractile function and regulation of cell viability, while mitochondrial dysfunction characterizes heart failure. The role of the UPRmt in the heart is unclear. Objectives The purpose of this study was to: 1) identify conditions that activate the UPRmt in the heart; and 2) study the relationship among the UPRmt, mitochondrial function, and cardiac contractile function. Methods Cultured cardiac myocytes were subjected to different stresses in vitro. Mice were subjected to chronic pressure overload. Tissues and blood biomarkers were studied in patients with aortic stenosis. Results Diverse neurohumoral or mitochondrial stresses transiently induced the UPRmt in cultured cardiomyocytes. The UPRmt was also induced in the hearts of mice subjected to chronic hemodynamic overload. Boosting the UPRmt with nicotinamide riboside (which augments NAD+ pools) in cardiomyocytes in vitro or hearts in vivo significantly mitigated the reductions in mitochondrial oxygen consumption induced by these stresses. In mice subjected to pressure overload, nicotinamide riboside reduced cardiomyocyte death and contractile dysfunction. Myocardial tissue from patients with aortic stenosis also showed evidence of UPRmt activation, which correlated with reduced tissue cardiomyocyte death and fibrosis and lower plasma levels of biomarkers of cardiac damage (high-sensitivity troponin T) and dysfunction (N-terminal pro–B-type natriuretic peptide). Conclusions These results identify the induction of the UPRmt in the mammalian (including human) heart exposed to pathological stresses. Enhancement of the UPRmt ameliorates mitochondrial and contractile dysfunction, suggesting that it may serve an important protective role in the stressed heart.Elsevier BVDadun. Depósito Académico Digital Universidad de Navarra20222022-03-1120192019-01-0120192019-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/63144reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/631442026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload |
| title |
Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload |
| spellingShingle |
Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload Smyrnias, I. (Ioannis)|||/items/d5ab339a-af96-4b6c-a384-6588f4d711a2 Cardiomyocyte Heart Mitochondria Pressure overload Unfolded protein response |
| title_short |
Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload |
| title_full |
Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload |
| title_fullStr |
Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload |
| title_full_unstemmed |
Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload |
| title_sort |
Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload |
| dc.creator.none.fl_str_mv |
Smyrnias, I. (Ioannis)|||/items/d5ab339a-af96-4b6c-a384-6588f4d711a2 Gray, S.P. (Stephen P.)|||/items/33ad7431-c580-46c5-928a-0d50a219dc7e Okonko, D. (Darlington)|||/items/d79a3fa8-adcf-4905-bc75-e4fcacb383f0 Sawyer, G. (Greta)|||/items/22d9a898-ace6-4a51-a94b-1d2b76ceb15d Zoccarato, A. (Anna)|||/items/bdd86a00-0deb-42de-a739-a2268fd2d6c0 Catibog, N. (Norman)|||/items/b2c6e5cc-a4b8-439c-919b-6b62d995c705 Lopez-Salazar, M.B. (María Begoña)|||/items/153e0e37-14b0-403e-afab-8af00c4edde0 Gonzalez, A. (Arantxa)|||/items/9c64c0f4-66b4-4b51-8593-0e50c091a515 Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1 Diez-Espino, J. (Javier)|||/items/125690ae-ba81-4d29-a748-e644f3584853 Shah, A.M. (Ajay M.)|||/items/3bc739ce-1498-4741-8de7-e054feba2801 |
| author |
Smyrnias, I. (Ioannis)|||/items/d5ab339a-af96-4b6c-a384-6588f4d711a2 |
| author_facet |
Smyrnias, I. (Ioannis)|||/items/d5ab339a-af96-4b6c-a384-6588f4d711a2 Gray, S.P. (Stephen P.)|||/items/33ad7431-c580-46c5-928a-0d50a219dc7e Okonko, D. (Darlington)|||/items/d79a3fa8-adcf-4905-bc75-e4fcacb383f0 Sawyer, G. (Greta)|||/items/22d9a898-ace6-4a51-a94b-1d2b76ceb15d Zoccarato, A. (Anna)|||/items/bdd86a00-0deb-42de-a739-a2268fd2d6c0 Catibog, N. (Norman)|||/items/b2c6e5cc-a4b8-439c-919b-6b62d995c705 Lopez-Salazar, M.B. (María Begoña)|||/items/153e0e37-14b0-403e-afab-8af00c4edde0 Gonzalez, A. (Arantxa)|||/items/9c64c0f4-66b4-4b51-8593-0e50c091a515 Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1 Diez-Espino, J. (Javier)|||/items/125690ae-ba81-4d29-a748-e644f3584853 Shah, A.M. (Ajay M.)|||/items/3bc739ce-1498-4741-8de7-e054feba2801 |
| author_role |
author |
| author2 |
Gray, S.P. (Stephen P.)|||/items/33ad7431-c580-46c5-928a-0d50a219dc7e Okonko, D. (Darlington)|||/items/d79a3fa8-adcf-4905-bc75-e4fcacb383f0 Sawyer, G. (Greta)|||/items/22d9a898-ace6-4a51-a94b-1d2b76ceb15d Zoccarato, A. (Anna)|||/items/bdd86a00-0deb-42de-a739-a2268fd2d6c0 Catibog, N. (Norman)|||/items/b2c6e5cc-a4b8-439c-919b-6b62d995c705 Lopez-Salazar, M.B. (María Begoña)|||/items/153e0e37-14b0-403e-afab-8af00c4edde0 Gonzalez, A. (Arantxa)|||/items/9c64c0f4-66b4-4b51-8593-0e50c091a515 Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1 Diez-Espino, J. (Javier)|||/items/125690ae-ba81-4d29-a748-e644f3584853 Shah, A.M. (Ajay M.)|||/items/3bc739ce-1498-4741-8de7-e054feba2801 |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Cardiomyocyte Heart Mitochondria Pressure overload Unfolded protein response |
| topic |
Cardiomyocyte Heart Mitochondria Pressure overload Unfolded protein response |
| description |
Background The mitochondrial unfolded protein response (UPRmt) is activated when misfolded proteins accumulate within mitochondria and leads to increased expression of mitochondrial chaperones and proteases to maintain protein quality and mitochondrial function. Cardiac mitochondria are essential for contractile function and regulation of cell viability, while mitochondrial dysfunction characterizes heart failure. The role of the UPRmt in the heart is unclear. Objectives The purpose of this study was to: 1) identify conditions that activate the UPRmt in the heart; and 2) study the relationship among the UPRmt, mitochondrial function, and cardiac contractile function. Methods Cultured cardiac myocytes were subjected to different stresses in vitro. Mice were subjected to chronic pressure overload. Tissues and blood biomarkers were studied in patients with aortic stenosis. Results Diverse neurohumoral or mitochondrial stresses transiently induced the UPRmt in cultured cardiomyocytes. The UPRmt was also induced in the hearts of mice subjected to chronic hemodynamic overload. Boosting the UPRmt with nicotinamide riboside (which augments NAD+ pools) in cardiomyocytes in vitro or hearts in vivo significantly mitigated the reductions in mitochondrial oxygen consumption induced by these stresses. In mice subjected to pressure overload, nicotinamide riboside reduced cardiomyocyte death and contractile dysfunction. Myocardial tissue from patients with aortic stenosis also showed evidence of UPRmt activation, which correlated with reduced tissue cardiomyocyte death and fibrosis and lower plasma levels of biomarkers of cardiac damage (high-sensitivity troponin T) and dysfunction (N-terminal pro–B-type natriuretic peptide). Conclusions These results identify the induction of the UPRmt in the mammalian (including human) heart exposed to pathological stresses. Enhancement of the UPRmt ameliorates mitochondrial and contractile dysfunction, suggesting that it may serve an important protective role in the stressed heart. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-01-01 2019 2019-01-01 2022 2022-03-11 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/63144 |
| url |
https://hdl.handle.net/10171/63144 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier BV |
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Elsevier BV |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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1869406912413433856 |
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15.301603 |