Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy

Autores
Donato, Pablo Martín; Buchholz, Bruno; Morales, Celina; Valdez, Laura Batriz; Zaobornyj, Tamara; Baratta, Sergio; Paez, Diamela T.; Matoso, Mirian; Vaccarino, Guillermo; Chejtman, Demian; Agüero, Oscar; Telayna, Juan; Navia, José; Hita, Alejandro; Boveris, Alberto Antonio; Gelpi, Ricardo Jorge
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Transition from compensated to decompensated left ventricular hypertrophy (LVH) is accompanied by functional and structural changes. Here, the aim was to evaluate dystrophin expression in murine models and human subjects with LVH by transverse aortic constriction (TAC) and aortic stenosis (AS), respectively. We determined whether doxycycline (Doxy) prevented dystrophin expression and myocardial stiffness in mice. Additionally, ventricular function recovery was evaluated in patients 1 year after surgery. Mice were subjected to TAC and monitored for 3 weeks. A second group received Doxy treatment after TAC. Patients with AS were stratified by normal left ventricular end-diastolic wall stress (LVEDWS) and high LVEDWS, and groups were compared. In mice, LVH decreased inotropism and increased myocardial stiffness associated with a dystrophin breakdown and a decreased mitochondrial O2 uptake (MitoMVO2). These alterations were attenuated by Doxy. Patients with high LVEDWS showed similar results to those observed in mice. A correlation between dystrophin and myocardial stiffness was observed in both mice and humans. Systolic function at 1 year post-surgery was only recovered in the normal-LVEDWS group. In summary, mice and humans present diastolic dysfunction associated with dystrophin degradation. The recovery of ventricular function was observed only in patients with normal LVEDWS and without dystrophin degradation. In mice, Doxy improved MitoMVO2. Based on our results it is concluded that the LVH with high LVEDWS is associated to a degradation of dystrophin and increase of myocardial stiffness. At least in a murine model these alterations were attenuated after the administration of a matrix metalloprotease inhibitor.
Fil: Donato, Pablo Martín. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Buchholz, Bruno. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Morales, Celina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Valdez, Laura Batriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Zaobornyj, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Baratta, Sergio. Hospital Austral; Argentina
Fil: Paez, Diamela T.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Matoso, Mirian. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Vaccarino, Guillermo. Hospital Austral; Argentina
Fil: Chejtman, Demian. Hospital Austral; Argentina
Fil: Agüero, Oscar. Hospital Austral; Argentina
Fil: Telayna, Juan. Hospital Austral; Argentina
Fil: Navia, José. Hospital Austral; Argentina
Fil: Hita, Alejandro. Hospital Austral; Argentina
Fil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Estenosis Aortica
Diastole
Ratones
Pacientes
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/47390
Acceder
id CONICETDig_f93de5df8068d7f3f5a2c2e540dfe3b1
oai_identifier_str oai:ri.conicet.gov.ar:11336/47390
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophyDonato, Pablo MartínBuchholz, BrunoMorales, CelinaValdez, Laura BatrizZaobornyj, TamaraBaratta, SergioPaez, Diamela T.Matoso, MirianVaccarino, GuillermoChejtman, DemianAgüero, OscarTelayna, JuanNavia, JoséHita, AlejandroBoveris, Alberto AntonioGelpi, Ricardo JorgeEstenosis AorticaDiastoleRatonesPacienteshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Transition from compensated to decompensated left ventricular hypertrophy (LVH) is accompanied by functional and structural changes. Here, the aim was to evaluate dystrophin expression in murine models and human subjects with LVH by transverse aortic constriction (TAC) and aortic stenosis (AS), respectively. We determined whether doxycycline (Doxy) prevented dystrophin expression and myocardial stiffness in mice. Additionally, ventricular function recovery was evaluated in patients 1 year after surgery. Mice were subjected to TAC and monitored for 3 weeks. A second group received Doxy treatment after TAC. Patients with AS were stratified by normal left ventricular end-diastolic wall stress (LVEDWS) and high LVEDWS, and groups were compared. In mice, LVH decreased inotropism and increased myocardial stiffness associated with a dystrophin breakdown and a decreased mitochondrial O2 uptake (MitoMVO2). These alterations were attenuated by Doxy. Patients with high LVEDWS showed similar results to those observed in mice. A correlation between dystrophin and myocardial stiffness was observed in both mice and humans. Systolic function at 1 year post-surgery was only recovered in the normal-LVEDWS group. In summary, mice and humans present diastolic dysfunction associated with dystrophin degradation. The recovery of ventricular function was observed only in patients with normal LVEDWS and without dystrophin degradation. In mice, Doxy improved MitoMVO2. Based on our results it is concluded that the LVH with high LVEDWS is associated to a degradation of dystrophin and increase of myocardial stiffness. At least in a murine model these alterations were attenuated after the administration of a matrix metalloprotease inhibitor.Fil: Donato, Pablo Martín. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Buchholz, Bruno. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morales, Celina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Valdez, Laura Batriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Zaobornyj, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Baratta, Sergio. Hospital Austral; ArgentinaFil: Paez, Diamela T.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Matoso, Mirian. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Vaccarino, Guillermo. Hospital Austral; ArgentinaFil: Chejtman, Demian. Hospital Austral; ArgentinaFil: Agüero, Oscar. Hospital Austral; ArgentinaFil: Telayna, Juan. Hospital Austral; ArgentinaFil: Navia, José. Hospital Austral; ArgentinaFil: Hita, Alejandro. Hospital Austral; ArgentinaFil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaSpringer2017-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47390Donato, Pablo Martín; Buchholz, Bruno; Morales, Celina; Valdez, Laura Batriz; Zaobornyj, Tamara; et al.; Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy; Springer; Molecular and Cellular Biochemistry; 432; 1-2; 3-2017; 169-1780300-81771573-4919CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s11010-017-3007-zinfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs11010-017-3007-zinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:51:16Zoai:ri.conicet.gov.ar:11336/47390instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:51:16.29CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy
title Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy
spellingShingle Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy
Donato, Pablo Martín
Estenosis Aortica
Diastole
Ratones
Pacientes
title_short Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy
title_full Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy
title_fullStr Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy
title_full_unstemmed Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy
title_sort Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy
dc.creator.none.fl_str_mv Donato, Pablo Martín
Buchholz, Bruno
Morales, Celina
Valdez, Laura Batriz
Zaobornyj, Tamara
Baratta, Sergio
Paez, Diamela T.
Matoso, Mirian
Vaccarino, Guillermo
Chejtman, Demian
Agüero, Oscar
Telayna, Juan
Navia, José
Hita, Alejandro
Boveris, Alberto Antonio
Gelpi, Ricardo Jorge
author Donato, Pablo Martín
author_facet Donato, Pablo Martín
Buchholz, Bruno
Morales, Celina
Valdez, Laura Batriz
Zaobornyj, Tamara
Baratta, Sergio
Paez, Diamela T.
Matoso, Mirian
Vaccarino, Guillermo
Chejtman, Demian
Agüero, Oscar
Telayna, Juan
Navia, José
Hita, Alejandro
Boveris, Alberto Antonio
Gelpi, Ricardo Jorge
author_role author
author2 Buchholz, Bruno
Morales, Celina
Valdez, Laura Batriz
Zaobornyj, Tamara
Baratta, Sergio
Paez, Diamela T.
Matoso, Mirian
Vaccarino, Guillermo
Chejtman, Demian
Agüero, Oscar
Telayna, Juan
Navia, José
Hita, Alejandro
Boveris, Alberto Antonio
Gelpi, Ricardo Jorge
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Estenosis Aortica
Diastole
Ratones
Pacientes
topic Estenosis Aortica
Diastole
Ratones
Pacientes
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Transition from compensated to decompensated left ventricular hypertrophy (LVH) is accompanied by functional and structural changes. Here, the aim was to evaluate dystrophin expression in murine models and human subjects with LVH by transverse aortic constriction (TAC) and aortic stenosis (AS), respectively. We determined whether doxycycline (Doxy) prevented dystrophin expression and myocardial stiffness in mice. Additionally, ventricular function recovery was evaluated in patients 1 year after surgery. Mice were subjected to TAC and monitored for 3 weeks. A second group received Doxy treatment after TAC. Patients with AS were stratified by normal left ventricular end-diastolic wall stress (LVEDWS) and high LVEDWS, and groups were compared. In mice, LVH decreased inotropism and increased myocardial stiffness associated with a dystrophin breakdown and a decreased mitochondrial O2 uptake (MitoMVO2). These alterations were attenuated by Doxy. Patients with high LVEDWS showed similar results to those observed in mice. A correlation between dystrophin and myocardial stiffness was observed in both mice and humans. Systolic function at 1 year post-surgery was only recovered in the normal-LVEDWS group. In summary, mice and humans present diastolic dysfunction associated with dystrophin degradation. The recovery of ventricular function was observed only in patients with normal LVEDWS and without dystrophin degradation. In mice, Doxy improved MitoMVO2. Based on our results it is concluded that the LVH with high LVEDWS is associated to a degradation of dystrophin and increase of myocardial stiffness. At least in a murine model these alterations were attenuated after the administration of a matrix metalloprotease inhibitor.
Fil: Donato, Pablo Martín. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Buchholz, Bruno. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Morales, Celina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Valdez, Laura Batriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Zaobornyj, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Baratta, Sergio. Hospital Austral; Argentina
Fil: Paez, Diamela T.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Matoso, Mirian. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Vaccarino, Guillermo. Hospital Austral; Argentina
Fil: Chejtman, Demian. Hospital Austral; Argentina
Fil: Agüero, Oscar. Hospital Austral; Argentina
Fil: Telayna, Juan. Hospital Austral; Argentina
Fil: Navia, José. Hospital Austral; Argentina
Fil: Hita, Alejandro. Hospital Austral; Argentina
Fil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Transition from compensated to decompensated left ventricular hypertrophy (LVH) is accompanied by functional and structural changes. Here, the aim was to evaluate dystrophin expression in murine models and human subjects with LVH by transverse aortic constriction (TAC) and aortic stenosis (AS), respectively. We determined whether doxycycline (Doxy) prevented dystrophin expression and myocardial stiffness in mice. Additionally, ventricular function recovery was evaluated in patients 1 year after surgery. Mice were subjected to TAC and monitored for 3 weeks. A second group received Doxy treatment after TAC. Patients with AS were stratified by normal left ventricular end-diastolic wall stress (LVEDWS) and high LVEDWS, and groups were compared. In mice, LVH decreased inotropism and increased myocardial stiffness associated with a dystrophin breakdown and a decreased mitochondrial O2 uptake (MitoMVO2). These alterations were attenuated by Doxy. Patients with high LVEDWS showed similar results to those observed in mice. A correlation between dystrophin and myocardial stiffness was observed in both mice and humans. Systolic function at 1 year post-surgery was only recovered in the normal-LVEDWS group. In summary, mice and humans present diastolic dysfunction associated with dystrophin degradation. The recovery of ventricular function was observed only in patients with normal LVEDWS and without dystrophin degradation. In mice, Doxy improved MitoMVO2. Based on our results it is concluded that the LVH with high LVEDWS is associated to a degradation of dystrophin and increase of myocardial stiffness. At least in a murine model these alterations were attenuated after the administration of a matrix metalloprotease inhibitor.
publishDate 2017
dc.date.none.fl_str_mv 2017-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/47390
Donato, Pablo Martín; Buchholz, Bruno; Morales, Celina; Valdez, Laura Batriz; Zaobornyj, Tamara; et al.; Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy; Springer; Molecular and Cellular Biochemistry; 432; 1-2; 3-2017; 169-178
0300-8177
1573-4919
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47390
identifier_str_mv Donato, Pablo Martín; Buchholz, Bruno; Morales, Celina; Valdez, Laura Batriz; Zaobornyj, Tamara; et al.; Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy; Springer; Molecular and Cellular Biochemistry; 432; 1-2; 3-2017; 169-178
0300-8177
1573-4919
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s11010-017-3007-z
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs11010-017-3007-z
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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