Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity

Autores
Yeves, Alejandra del Milagro; Burgos, Juan Ignacio; Caicedo Medina, Julian Alberto; Villa-Abrille, María Celeste; Ennis, Irene Lucia
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Aim: Myocardial Na+/H+ exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF-1—key humoral mediator of exercise training—inhibits myocardial NHE-1, at least in normotensive rats. Therefore, we hypothesize that IGF-1 by hampering NHE-1 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR. Methods: NHE-1 activity [proton efflux (JH+) mmol L−1 min−1], expression and phosphorylation; H2O2 production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence/absence of IGF-1. Results: IGF-1 significantly decreased NHE-1 activity (JH+ at pHi 6.95: 1.39 ± 0.32, n = 9 vs C 3.27 ± 0.3, n = 20, P <.05); effect prevented by AG1024, an antagonist of IGF-1 receptor (2.7 ± 0.4, n = 7); by the PI3K inhibitor wortmannin (3.14 ± 0.41, n = 7); and the AKT inhibitor MK2206 (3.37 ± 0.43, n = 14). Moreover, IGF-1 exerted an antioxidant effect revealed by a significant reduction in H2O2 production accompanied by an increase in SOD activity. In addition, IGF-1 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients. Conclusion: IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players.
Fil: Yeves, Alejandra del Milagro. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
Fil: Burgos, Juan Ignacio. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
Fil: Caicedo Medina, Julian Alberto. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
Fil: Villa-Abrille, María Celeste. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
Fil: Ennis, Irene Lucia. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
Materia
CONTRACTILITY
HYPERTENSION
INSULIN-LIKE GROWTH FACTOR 1
NHE-1
OXIDATIVE STRESS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/95514
Acceder
id CONICETDig_19b0e7c415b2beb1139dbbb602fc8576
oai_identifier_str oai:ri.conicet.gov.ar:11336/95514
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activityYeves, Alejandra del MilagroBurgos, Juan IgnacioCaicedo Medina, Julian AlbertoVilla-Abrille, María CelesteEnnis, Irene LuciaCONTRACTILITYHYPERTENSIONINSULIN-LIKE GROWTH FACTOR 1NHE-1OXIDATIVE STRESShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Aim: Myocardial Na+/H+ exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF-1—key humoral mediator of exercise training—inhibits myocardial NHE-1, at least in normotensive rats. Therefore, we hypothesize that IGF-1 by hampering NHE-1 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR. Methods: NHE-1 activity [proton efflux (JH+) mmol L−1 min−1], expression and phosphorylation; H2O2 production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence/absence of IGF-1. Results: IGF-1 significantly decreased NHE-1 activity (JH+ at pHi 6.95: 1.39 ± 0.32, n = 9 vs C 3.27 ± 0.3, n = 20, P <.05); effect prevented by AG1024, an antagonist of IGF-1 receptor (2.7 ± 0.4, n = 7); by the PI3K inhibitor wortmannin (3.14 ± 0.41, n = 7); and the AKT inhibitor MK2206 (3.37 ± 0.43, n = 14). Moreover, IGF-1 exerted an antioxidant effect revealed by a significant reduction in H2O2 production accompanied by an increase in SOD activity. In addition, IGF-1 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients. Conclusion: IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players.Fil: Yeves, Alejandra del Milagro. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); ArgentinaFil: Burgos, Juan Ignacio. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); ArgentinaFil: Caicedo Medina, Julian Alberto. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); ArgentinaFil: Villa-Abrille, María Celeste. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); ArgentinaFil: Ennis, Irene Lucia. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); ArgentinaWiley Blackwell Publishing, Inc2018-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95514Yeves, Alejandra del Milagro; Burgos, Juan Ignacio; Caicedo Medina, Julian Alberto; Villa-Abrille, María Celeste; Ennis, Irene Lucia; Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity; Wiley Blackwell Publishing, Inc; Acta Physiologica; 224; 2; 10-2018; 1-131748-1708CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/apha.13092info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/apha.13092info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:19:54Zoai:ri.conicet.gov.ar:11336/95514instacron: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:34982025-10-22 12:19:54.434CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity
title Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity
spellingShingle Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity
Yeves, Alejandra del Milagro
CONTRACTILITY
HYPERTENSION
INSULIN-LIKE GROWTH FACTOR 1
NHE-1
OXIDATIVE STRESS
title_short Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity
title_full Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity
title_fullStr Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity
title_full_unstemmed Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity
title_sort Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity
dc.creator.none.fl_str_mv Yeves, Alejandra del Milagro
Burgos, Juan Ignacio
Caicedo Medina, Julian Alberto
Villa-Abrille, María Celeste
Ennis, Irene Lucia
author Yeves, Alejandra del Milagro
author_facet Yeves, Alejandra del Milagro
Burgos, Juan Ignacio
Caicedo Medina, Julian Alberto
Villa-Abrille, María Celeste
Ennis, Irene Lucia
author_role author
author2 Burgos, Juan Ignacio
Caicedo Medina, Julian Alberto
Villa-Abrille, María Celeste
Ennis, Irene Lucia
author2_role author
author
author
author
dc.subject.none.fl_str_mv CONTRACTILITY
HYPERTENSION
INSULIN-LIKE GROWTH FACTOR 1
NHE-1
OXIDATIVE STRESS
topic CONTRACTILITY
HYPERTENSION
INSULIN-LIKE GROWTH FACTOR 1
NHE-1
OXIDATIVE STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Aim: Myocardial Na+/H+ exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF-1—key humoral mediator of exercise training—inhibits myocardial NHE-1, at least in normotensive rats. Therefore, we hypothesize that IGF-1 by hampering NHE-1 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR. Methods: NHE-1 activity [proton efflux (JH+) mmol L−1 min−1], expression and phosphorylation; H2O2 production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence/absence of IGF-1. Results: IGF-1 significantly decreased NHE-1 activity (JH+ at pHi 6.95: 1.39 ± 0.32, n = 9 vs C 3.27 ± 0.3, n = 20, P <.05); effect prevented by AG1024, an antagonist of IGF-1 receptor (2.7 ± 0.4, n = 7); by the PI3K inhibitor wortmannin (3.14 ± 0.41, n = 7); and the AKT inhibitor MK2206 (3.37 ± 0.43, n = 14). Moreover, IGF-1 exerted an antioxidant effect revealed by a significant reduction in H2O2 production accompanied by an increase in SOD activity. In addition, IGF-1 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients. Conclusion: IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players.
Fil: Yeves, Alejandra del Milagro. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
Fil: Burgos, Juan Ignacio. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
Fil: Caicedo Medina, Julian Alberto. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
Fil: Villa-Abrille, María Celeste. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
Fil: Ennis, Irene Lucia. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentina
description Aim: Myocardial Na+/H+ exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF-1—key humoral mediator of exercise training—inhibits myocardial NHE-1, at least in normotensive rats. Therefore, we hypothesize that IGF-1 by hampering NHE-1 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR. Methods: NHE-1 activity [proton efflux (JH+) mmol L−1 min−1], expression and phosphorylation; H2O2 production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence/absence of IGF-1. Results: IGF-1 significantly decreased NHE-1 activity (JH+ at pHi 6.95: 1.39 ± 0.32, n = 9 vs C 3.27 ± 0.3, n = 20, P <.05); effect prevented by AG1024, an antagonist of IGF-1 receptor (2.7 ± 0.4, n = 7); by the PI3K inhibitor wortmannin (3.14 ± 0.41, n = 7); and the AKT inhibitor MK2206 (3.37 ± 0.43, n = 14). Moreover, IGF-1 exerted an antioxidant effect revealed by a significant reduction in H2O2 production accompanied by an increase in SOD activity. In addition, IGF-1 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients. Conclusion: IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players.
publishDate 2018
dc.date.none.fl_str_mv 2018-10
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/11336/95514
Yeves, Alejandra del Milagro; Burgos, Juan Ignacio; Caicedo Medina, Julian Alberto; Villa-Abrille, María Celeste; Ennis, Irene Lucia; Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity; Wiley Blackwell Publishing, Inc; Acta Physiologica; 224; 2; 10-2018; 1-13
1748-1708
CONICET Digital
CONICET
url http://hdl.handle.net/11336/95514
identifier_str_mv Yeves, Alejandra del Milagro; Burgos, Juan Ignacio; Caicedo Medina, Julian Alberto; Villa-Abrille, María Celeste; Ennis, Irene Lucia; Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity; Wiley Blackwell Publishing, Inc; Acta Physiologica; 224; 2; 10-2018; 1-13
1748-1708
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/apha.13092
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/apha.13092
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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
_version_ 1846782641629560832
score 12.982451

Publicaciones similares