Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II

Autores
Medina, Andrés Javier; Pinilla, Oscar Andres; Portiansky, Enrique Leo; Caldiz, Claudia Irma; Ennis, Irene Lucia
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chronic activation of the renin angiotensin system (RAS) favors several cardiac diseases, among which myocardial hypertrophy occupies an outstanding place. In this context, the hyperactivity of the cardiac Na+/H+ (NHE-1) exchanger plays a key role. The pathologic remodeling of the myocardium constitutes an independent risk factor for morbidity and mortality with continuously increasing healthcare cost. Therefore, the development of better therapeutic strategies emerges as highly mandatory. Our goal was to prevent angiotensin II (ANGII)-induced cardiac hypertrophy by NHE-1 gene silencing in Wistar rats. The intramyocardial injection of a lentivirus coding a specific small interference RNA (l-shNHE1) significantly reduced NHE-1 expression exclusively in the heart (~ 50 %) and prevented cardiac remodeling in rats exposed to chronic infusion of ANG II (heart weigh/tibia length: 24,03 ± 0,7915 mg/mm vs 28,45 ± 0,9779 mg/mm and collagen volume fraction 2,526 ± 0,5003 vs 5,982 ± 1,043 in l-shNHE1 + ANGII and ANGII, respectively).Interestingly, this was accompanied by an improvement in cardiac function determined by echocardiography even though blood pressure remained elevated (Fractional shortening 0,5960 ± 0,4228 vs -0,9567± 0,06888 and blood pressure at the end of ANGII treatment 141,2 ± 6,117 mm Hg vs 134,1 ± 6,723 mm Hg ; in l-shNHE1 + ANGII and ANGII, respectively). ANGII infusion increased myocardial NADPH oxidase activity but the l-shNHE1 injection prevented oxidative stressas revealed by the normalization of lipid peroxidation (T-BARS 12,40 ± 2,887.vs 23,05 ± 1,537 in lshNHE1 + ANGII and ANGII, respectively). These results allow as to propose the partial silencing of the cardiac NHE-1 through lentiviralinjection as a promising tool in the prevention of ANGII-induced cardiac hypertrophy.
Fil: Medina, Andrés Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Pinilla, Oscar Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Caldiz, Claudia Irma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Materia
ANGIOTENSIN II
CARDIAC HYPERTROPHY
LENTIVIRUS
NHE-1
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:11336/105394
Acceder
id CONICETDig_6ae9599497c4df1275cf8fe503f3696f
oai_identifier_str oai:ri.conicet.gov.ar:11336/105394
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin IIMedina, Andrés JavierPinilla, Oscar AndresPortiansky, Enrique LeoCaldiz, Claudia IrmaEnnis, Irene LuciaANGIOTENSIN IICARDIAC HYPERTROPHYLENTIVIRUSNHE-1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Chronic activation of the renin angiotensin system (RAS) favors several cardiac diseases, among which myocardial hypertrophy occupies an outstanding place. In this context, the hyperactivity of the cardiac Na+/H+ (NHE-1) exchanger plays a key role. The pathologic remodeling of the myocardium constitutes an independent risk factor for morbidity and mortality with continuously increasing healthcare cost. Therefore, the development of better therapeutic strategies emerges as highly mandatory. Our goal was to prevent angiotensin II (ANGII)-induced cardiac hypertrophy by NHE-1 gene silencing in Wistar rats. The intramyocardial injection of a lentivirus coding a specific small interference RNA (l-shNHE1) significantly reduced NHE-1 expression exclusively in the heart (~ 50 %) and prevented cardiac remodeling in rats exposed to chronic infusion of ANG II (heart weigh/tibia length: 24,03 ± 0,7915 mg/mm vs 28,45 ± 0,9779 mg/mm and collagen volume fraction 2,526 ± 0,5003 vs 5,982 ± 1,043 in l-shNHE1 + ANGII and ANGII, respectively).Interestingly, this was accompanied by an improvement in cardiac function determined by echocardiography even though blood pressure remained elevated (Fractional shortening 0,5960 ± 0,4228 vs -0,9567± 0,06888 and blood pressure at the end of ANGII treatment 141,2 ± 6,117 mm Hg vs 134,1 ± 6,723 mm Hg ; in l-shNHE1 + ANGII and ANGII, respectively). ANGII infusion increased myocardial NADPH oxidase activity but the l-shNHE1 injection prevented oxidative stressas revealed by the normalization of lipid peroxidation (T-BARS 12,40 ± 2,887.vs 23,05 ± 1,537 in lshNHE1 + ANGII and ANGII, respectively). These results allow as to propose the partial silencing of the cardiac NHE-1 through lentiviralinjection as a promising tool in the prevention of ANGII-induced cardiac hypertrophy.Fil: Medina, Andrés Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Pinilla, Oscar Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Caldiz, Claudia Irma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaAcademic Press Inc Elsevier Science2019-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/105394Medina, Andrés Javier; Pinilla, Oscar Andres; Portiansky, Enrique Leo; Caldiz, Claudia Irma; Ennis, Irene Lucia; Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II; Academic Press Inc Elsevier Science; Experimental and Molecular Pathology; 107; 4-2019; 1-90014-4800CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0014480018303691info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexmp.2019.01.007info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:34Zoai:ri.conicet.gov.ar:11336/105394instacron: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:34982025-09-03 09:48:35.181CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II
title Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II
spellingShingle Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II
Medina, Andrés Javier
ANGIOTENSIN II
CARDIAC HYPERTROPHY
LENTIVIRUS
NHE-1
title_short Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II
title_full Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II
title_fullStr Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II
title_full_unstemmed Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II
title_sort Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II
dc.creator.none.fl_str_mv Medina, Andrés Javier
Pinilla, Oscar Andres
Portiansky, Enrique Leo
Caldiz, Claudia Irma
Ennis, Irene Lucia
author Medina, Andrés Javier
author_facet Medina, Andrés Javier
Pinilla, Oscar Andres
Portiansky, Enrique Leo
Caldiz, Claudia Irma
Ennis, Irene Lucia
author_role author
author2 Pinilla, Oscar Andres
Portiansky, Enrique Leo
Caldiz, Claudia Irma
Ennis, Irene Lucia
author2_role author
author
author
author
dc.subject.none.fl_str_mv ANGIOTENSIN II
CARDIAC HYPERTROPHY
LENTIVIRUS
NHE-1
topic ANGIOTENSIN II
CARDIAC HYPERTROPHY
LENTIVIRUS
NHE-1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chronic activation of the renin angiotensin system (RAS) favors several cardiac diseases, among which myocardial hypertrophy occupies an outstanding place. In this context, the hyperactivity of the cardiac Na+/H+ (NHE-1) exchanger plays a key role. The pathologic remodeling of the myocardium constitutes an independent risk factor for morbidity and mortality with continuously increasing healthcare cost. Therefore, the development of better therapeutic strategies emerges as highly mandatory. Our goal was to prevent angiotensin II (ANGII)-induced cardiac hypertrophy by NHE-1 gene silencing in Wistar rats. The intramyocardial injection of a lentivirus coding a specific small interference RNA (l-shNHE1) significantly reduced NHE-1 expression exclusively in the heart (~ 50 %) and prevented cardiac remodeling in rats exposed to chronic infusion of ANG II (heart weigh/tibia length: 24,03 ± 0,7915 mg/mm vs 28,45 ± 0,9779 mg/mm and collagen volume fraction 2,526 ± 0,5003 vs 5,982 ± 1,043 in l-shNHE1 + ANGII and ANGII, respectively).Interestingly, this was accompanied by an improvement in cardiac function determined by echocardiography even though blood pressure remained elevated (Fractional shortening 0,5960 ± 0,4228 vs -0,9567± 0,06888 and blood pressure at the end of ANGII treatment 141,2 ± 6,117 mm Hg vs 134,1 ± 6,723 mm Hg ; in l-shNHE1 + ANGII and ANGII, respectively). ANGII infusion increased myocardial NADPH oxidase activity but the l-shNHE1 injection prevented oxidative stressas revealed by the normalization of lipid peroxidation (T-BARS 12,40 ± 2,887.vs 23,05 ± 1,537 in lshNHE1 + ANGII and ANGII, respectively). These results allow as to propose the partial silencing of the cardiac NHE-1 through lentiviralinjection as a promising tool in the prevention of ANGII-induced cardiac hypertrophy.
Fil: Medina, Andrés Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Pinilla, Oscar Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina
Fil: Caldiz, Claudia Irma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
description Chronic activation of the renin angiotensin system (RAS) favors several cardiac diseases, among which myocardial hypertrophy occupies an outstanding place. In this context, the hyperactivity of the cardiac Na+/H+ (NHE-1) exchanger plays a key role. The pathologic remodeling of the myocardium constitutes an independent risk factor for morbidity and mortality with continuously increasing healthcare cost. Therefore, the development of better therapeutic strategies emerges as highly mandatory. Our goal was to prevent angiotensin II (ANGII)-induced cardiac hypertrophy by NHE-1 gene silencing in Wistar rats. The intramyocardial injection of a lentivirus coding a specific small interference RNA (l-shNHE1) significantly reduced NHE-1 expression exclusively in the heart (~ 50 %) and prevented cardiac remodeling in rats exposed to chronic infusion of ANG II (heart weigh/tibia length: 24,03 ± 0,7915 mg/mm vs 28,45 ± 0,9779 mg/mm and collagen volume fraction 2,526 ± 0,5003 vs 5,982 ± 1,043 in l-shNHE1 + ANGII and ANGII, respectively).Interestingly, this was accompanied by an improvement in cardiac function determined by echocardiography even though blood pressure remained elevated (Fractional shortening 0,5960 ± 0,4228 vs -0,9567± 0,06888 and blood pressure at the end of ANGII treatment 141,2 ± 6,117 mm Hg vs 134,1 ± 6,723 mm Hg ; in l-shNHE1 + ANGII and ANGII, respectively). ANGII infusion increased myocardial NADPH oxidase activity but the l-shNHE1 injection prevented oxidative stressas revealed by the normalization of lipid peroxidation (T-BARS 12,40 ± 2,887.vs 23,05 ± 1,537 in lshNHE1 + ANGII and ANGII, respectively). These results allow as to propose the partial silencing of the cardiac NHE-1 through lentiviralinjection as a promising tool in the prevention of ANGII-induced cardiac hypertrophy.
publishDate 2019
dc.date.none.fl_str_mv 2019-04
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/11336/105394
Medina, Andrés Javier; Pinilla, Oscar Andres; Portiansky, Enrique Leo; Caldiz, Claudia Irma; Ennis, Irene Lucia; Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II; Academic Press Inc Elsevier Science; Experimental and Molecular Pathology; 107; 4-2019; 1-9
0014-4800
CONICET Digital
CONICET
url http://hdl.handle.net/11336/105394
identifier_str_mv Medina, Andrés Javier; Pinilla, Oscar Andres; Portiansky, Enrique Leo; Caldiz, Claudia Irma; Ennis, Irene Lucia; Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II; Academic Press Inc Elsevier Science; Experimental and Molecular Pathology; 107; 4-2019; 1-9
0014-4800
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0014480018303691
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexmp.2019.01.007
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
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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 13.13397

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