Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown to prevent heart failure progression, although the mechanisms remain poorly understood. Here we evaluated the effect of empagliflozin (EMPA, SGLT2i) in cardiac remodeling after myocardial infarction, the interplay with diabetes status an...

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Autores: Asensio Lopez, Maria Del Carmen, Lax, Antonio, Hernandez Vicente, Alvaro, Saura Guillen, Elena, Hernandez-Martinez, Antonio, Fernandez Del Palacio, Maria Josefa, Bayes-Genis, Antoni, Pascual-Figal, Domingo A
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/12869
Acceso en línea:http://hdl.handle.net/20.500.12105/12869
Access Level:acceso abierto
Palabra clave:Animals
Benzhydryl Compounds
Diabetes Mellitus, Experimental
GTP Cyclohydrolase
Glucosides
Male
Myocardial Infarction
Rats
Rats, Wistar
Sodium-Glucose Transporter 2 Inhibitors
Ventricular Dysfunction, Left
Ventricular Remodeling
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/12869
network_acronym_str ES
network_name_str España
repository_id_str
spelling Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.Asensio Lopez, Maria Del CarmenLax, AntonioHernandez Vicente, AlvaroSaura Guillen, ElenaHernandez-Martinez, AntonioFernandez Del Palacio, Maria JosefaBayes-Genis, AntoniPascual-Figal, Domingo AAnimalsBenzhydryl CompoundsDiabetes Mellitus, ExperimentalGTP CyclohydrolaseGlucosidesMaleMyocardial InfarctionRatsRats, WistarSodium-Glucose Transporter 2 InhibitorsVentricular Dysfunction, LeftVentricular RemodelingSodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown to prevent heart failure progression, although the mechanisms remain poorly understood. Here we evaluated the effect of empagliflozin (EMPA, SGLT2i) in cardiac remodeling after myocardial infarction, the interplay with diabetes status and the role of cardiac GTP enzyme cyclohydrolase 1 (cGCH1). A rat model of diabetes (50 mg/kg streptozotocin, i.p.) was subjected to myocardial infarction and left ventricular systolic dysfunction, by ligation of the left anterior descending coronary artery. EMPA therapy significantly improved cardiac remodeling parameters and ameliorated processes of fibrosis and hypertrophy, in both non-diabetic and diabetic rats. This cardioprotective effect related with a significant increase in myocardial expression levels of cGCH1, which led to activation of nNOS and eNOS, and inhibition of iNOS, and subsequently resulted in increasing of NO levels and decreasing O2.- and nitrotyrosine levels. These effects were replicated in a cardiomyocyte biomechanical stretching diabetic model, where silencing cGCH1 blocked the preventive effect of EMPA. The beneficial effects were observed irrespective of diabetes status, although the magnitude was greater in presence of diabetes. Empagliflozin improves myocardial remodeling after myocardial infarction through overexpression of cGCH1, and irrespective of diabetes status.Nature Publishing GroupInstituto de Salud Carlos IIIFundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia20212021-05-0520202020-08-0120202020-08-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/mswordhttp://hdl.handle.net/20.500.12105/12869reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES 20652 JLIES PI19 00519open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/128692026-06-12T12:43:37Z
dc.title.none.fl_str_mv Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.
title Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.
spellingShingle Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.
Asensio Lopez, Maria Del Carmen
Animals
Benzhydryl Compounds
Diabetes Mellitus, Experimental
GTP Cyclohydrolase
Glucosides
Male
Myocardial Infarction
Rats
Rats, Wistar
Sodium-Glucose Transporter 2 Inhibitors
Ventricular Dysfunction, Left
Ventricular Remodeling
title_short Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.
title_full Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.
title_fullStr Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.
title_full_unstemmed Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.
title_sort Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.
dc.creator.none.fl_str_mv Asensio Lopez, Maria Del Carmen
Lax, Antonio
Hernandez Vicente, Alvaro
Saura Guillen, Elena
Hernandez-Martinez, Antonio
Fernandez Del Palacio, Maria Josefa
Bayes-Genis, Antoni
Pascual-Figal, Domingo A
author Asensio Lopez, Maria Del Carmen
author_facet Asensio Lopez, Maria Del Carmen
Lax, Antonio
Hernandez Vicente, Alvaro
Saura Guillen, Elena
Hernandez-Martinez, Antonio
Fernandez Del Palacio, Maria Josefa
Bayes-Genis, Antoni
Pascual-Figal, Domingo A
author_role author
author2 Lax, Antonio
Hernandez Vicente, Alvaro
Saura Guillen, Elena
Hernandez-Martinez, Antonio
Fernandez Del Palacio, Maria Josefa
Bayes-Genis, Antoni
Pascual-Figal, Domingo A
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia
dc.subject.none.fl_str_mv Animals
Benzhydryl Compounds
Diabetes Mellitus, Experimental
GTP Cyclohydrolase
Glucosides
Male
Myocardial Infarction
Rats
Rats, Wistar
Sodium-Glucose Transporter 2 Inhibitors
Ventricular Dysfunction, Left
Ventricular Remodeling
topic Animals
Benzhydryl Compounds
Diabetes Mellitus, Experimental
GTP Cyclohydrolase
Glucosides
Male
Myocardial Infarction
Rats
Rats, Wistar
Sodium-Glucose Transporter 2 Inhibitors
Ventricular Dysfunction, Left
Ventricular Remodeling
description Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown to prevent heart failure progression, although the mechanisms remain poorly understood. Here we evaluated the effect of empagliflozin (EMPA, SGLT2i) in cardiac remodeling after myocardial infarction, the interplay with diabetes status and the role of cardiac GTP enzyme cyclohydrolase 1 (cGCH1). A rat model of diabetes (50 mg/kg streptozotocin, i.p.) was subjected to myocardial infarction and left ventricular systolic dysfunction, by ligation of the left anterior descending coronary artery. EMPA therapy significantly improved cardiac remodeling parameters and ameliorated processes of fibrosis and hypertrophy, in both non-diabetic and diabetic rats. This cardioprotective effect related with a significant increase in myocardial expression levels of cGCH1, which led to activation of nNOS and eNOS, and inhibition of iNOS, and subsequently resulted in increasing of NO levels and decreasing O2.- and nitrotyrosine levels. These effects were replicated in a cardiomyocyte biomechanical stretching diabetic model, where silencing cGCH1 blocked the preventive effect of EMPA. The beneficial effects were observed irrespective of diabetes status, although the magnitude was greater in presence of diabetes. Empagliflozin improves myocardial remodeling after myocardial infarction through overexpression of cGCH1, and irrespective of diabetes status.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-08-01
2020
2020-08-01
2021
2021-05-05
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/12869
url http://hdl.handle.net/20.500.12105/12869
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES 20652 JLI
ES PI19 00519
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/msword
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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