Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart

Autores
Schuman, Mariano Luis; Peres Diaz, Ludmila Soledad; Landa, Maria Silvina; Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Alvarez, Azucena L.; Finkielman, Samuel; Pirola, Carlos Jose; Garcia, Silvia Ines
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Thyrotropin-releasing hormone (TRH) hyperactivity has been observed in the left ventricle of spontaneously hypertensive rats. Its long-term inhibition suppresses the development of hypertrophy, specifically preventing fibrosis. The presence of diverse systemic abnormalities in spontaneously hypertensive rat hearts has raised the question of whether specific TRH overexpression might be capable of inducing structural changes in favor of the hypertrophic phenotype in normal rat hearts. We produced TRH overexpression in normal rats by injecting into their left ventricular wall a plasmid driving expression of the preproTRH gene (PCMV-TRH). TRH content and expression of preproTRH, collagen type III, brain natriuretic peptide, β-myosin heavy chain, Bax-to-Bcl-2 ratio, and caspase-3 were measured. The overexpression maneuver was a success, as we found a significant increase in both tripeptide and preproTRH mRNA levels in the PCMV-TRH group compared with the control group. Immunohistochemical staining against TRH showed markedly positive brown signals only in the PCMV-TRH group. TRH overexpression induced a significant increase in fibrosis, evident in the increase of collagen type III expression accompanied by a significant increase in extracellular matrix expansion. We found a significant increase in brain natriuretic peptide and β-myosin heavy chain expression (recognized markers of hypertrophy). Moreover, TRH overexpression induced a slight but significant increase in myocyte diameter, indicating the onset of cell hypertrophy. We confirmed the data “in vitro” using primary cardiac cell cultures (fibroblasts and myocytes). In conclusion, these results show that a specific TRH increase in the left ventricle induced structural changes in the normal heart, thus making the cardiac TRH system a promising therapeutic target.
Fil: Schuman, Mariano Luis. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Peres Diaz, Ludmila Soledad. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Landa, Maria Silvina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Toblli, Jorge Eduardo. Hospital Aleman; Argentina
Fil: Cao, Gabriel Fernando. Hospital Aleman; Argentina
Fil: Alvarez, Azucena L.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Finkielman, Samuel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Pirola, Carlos Jose. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Garcia, Silvia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Materia
Trh
Fibrosis
Heart
Rat
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:11336/7807
Acceder
id CONICETDig_6b85d23539fb349d833d91002f0ef5ba
oai_identifier_str oai:ri.conicet.gov.ar:11336/7807
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heartSchuman, Mariano LuisPeres Diaz, Ludmila SoledadLanda, Maria SilvinaToblli, Jorge EduardoCao, Gabriel FernandoAlvarez, Azucena L.Finkielman, SamuelPirola, Carlos JoseGarcia, Silvia InesTrhFibrosisHeartRathttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Thyrotropin-releasing hormone (TRH) hyperactivity has been observed in the left ventricle of spontaneously hypertensive rats. Its long-term inhibition suppresses the development of hypertrophy, specifically preventing fibrosis. The presence of diverse systemic abnormalities in spontaneously hypertensive rat hearts has raised the question of whether specific TRH overexpression might be capable of inducing structural changes in favor of the hypertrophic phenotype in normal rat hearts. We produced TRH overexpression in normal rats by injecting into their left ventricular wall a plasmid driving expression of the preproTRH gene (PCMV-TRH). TRH content and expression of preproTRH, collagen type III, brain natriuretic peptide, β-myosin heavy chain, Bax-to-Bcl-2 ratio, and caspase-3 were measured. The overexpression maneuver was a success, as we found a significant increase in both tripeptide and preproTRH mRNA levels in the PCMV-TRH group compared with the control group. Immunohistochemical staining against TRH showed markedly positive brown signals only in the PCMV-TRH group. TRH overexpression induced a significant increase in fibrosis, evident in the increase of collagen type III expression accompanied by a significant increase in extracellular matrix expansion. We found a significant increase in brain natriuretic peptide and β-myosin heavy chain expression (recognized markers of hypertrophy). Moreover, TRH overexpression induced a slight but significant increase in myocyte diameter, indicating the onset of cell hypertrophy. We confirmed the data “in vitro” using primary cardiac cell cultures (fibroblasts and myocytes). In conclusion, these results show that a specific TRH increase in the left ventricle induced structural changes in the normal heart, thus making the cardiac TRH system a promising therapeutic target.Fil: Schuman, Mariano Luis. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Peres Diaz, Ludmila Soledad. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Landa, Maria Silvina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Toblli, Jorge Eduardo. Hospital Aleman; ArgentinaFil: Cao, Gabriel Fernando. Hospital Aleman; ArgentinaFil: Alvarez, Azucena L.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Finkielman, Samuel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Pirola, Carlos Jose. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Garcia, Silvia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaAmerican Physiological Society2014-10info: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/11336/7807Schuman, Mariano Luis; Peres Diaz, Ludmila Soledad; Landa, Maria Silvina; Toblli, Jorge Eduardo; Cao, Gabriel Fernando; et al.; Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart; American Physiological Society; American Journal Of Physiology-heart And Circulatory Physiology; 307; 11; 10-2014; 1667-16740363-6135enginfo:eu-repo/semantics/altIdentifier/url/http://ajpheart.physiology.org/content/307/11/H1667.longinfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajpheart.00494.2014info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:48Zoai:ri.conicet.gov.ar:11336/7807instacron: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 09:59:48.64CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
title Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
spellingShingle Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
Schuman, Mariano Luis
Trh
Fibrosis
Heart
Rat
title_short Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
title_full Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
title_fullStr Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
title_full_unstemmed Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
title_sort Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
dc.creator.none.fl_str_mv Schuman, Mariano Luis
Peres Diaz, Ludmila Soledad
Landa, Maria Silvina
Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Alvarez, Azucena L.
Finkielman, Samuel
Pirola, Carlos Jose
Garcia, Silvia Ines
author Schuman, Mariano Luis
author_facet Schuman, Mariano Luis
Peres Diaz, Ludmila Soledad
Landa, Maria Silvina
Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Alvarez, Azucena L.
Finkielman, Samuel
Pirola, Carlos Jose
Garcia, Silvia Ines
author_role author
author2 Peres Diaz, Ludmila Soledad
Landa, Maria Silvina
Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Alvarez, Azucena L.
Finkielman, Samuel
Pirola, Carlos Jose
Garcia, Silvia Ines
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trh
Fibrosis
Heart
Rat
topic Trh
Fibrosis
Heart
Rat
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Thyrotropin-releasing hormone (TRH) hyperactivity has been observed in the left ventricle of spontaneously hypertensive rats. Its long-term inhibition suppresses the development of hypertrophy, specifically preventing fibrosis. The presence of diverse systemic abnormalities in spontaneously hypertensive rat hearts has raised the question of whether specific TRH overexpression might be capable of inducing structural changes in favor of the hypertrophic phenotype in normal rat hearts. We produced TRH overexpression in normal rats by injecting into their left ventricular wall a plasmid driving expression of the preproTRH gene (PCMV-TRH). TRH content and expression of preproTRH, collagen type III, brain natriuretic peptide, β-myosin heavy chain, Bax-to-Bcl-2 ratio, and caspase-3 were measured. The overexpression maneuver was a success, as we found a significant increase in both tripeptide and preproTRH mRNA levels in the PCMV-TRH group compared with the control group. Immunohistochemical staining against TRH showed markedly positive brown signals only in the PCMV-TRH group. TRH overexpression induced a significant increase in fibrosis, evident in the increase of collagen type III expression accompanied by a significant increase in extracellular matrix expansion. We found a significant increase in brain natriuretic peptide and β-myosin heavy chain expression (recognized markers of hypertrophy). Moreover, TRH overexpression induced a slight but significant increase in myocyte diameter, indicating the onset of cell hypertrophy. We confirmed the data “in vitro” using primary cardiac cell cultures (fibroblasts and myocytes). In conclusion, these results show that a specific TRH increase in the left ventricle induced structural changes in the normal heart, thus making the cardiac TRH system a promising therapeutic target.
Fil: Schuman, Mariano Luis. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Peres Diaz, Ludmila Soledad. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Landa, Maria Silvina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Toblli, Jorge Eduardo. Hospital Aleman; Argentina
Fil: Cao, Gabriel Fernando. Hospital Aleman; Argentina
Fil: Alvarez, Azucena L.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Finkielman, Samuel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Pirola, Carlos Jose. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
Fil: Garcia, Silvia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
description Thyrotropin-releasing hormone (TRH) hyperactivity has been observed in the left ventricle of spontaneously hypertensive rats. Its long-term inhibition suppresses the development of hypertrophy, specifically preventing fibrosis. The presence of diverse systemic abnormalities in spontaneously hypertensive rat hearts has raised the question of whether specific TRH overexpression might be capable of inducing structural changes in favor of the hypertrophic phenotype in normal rat hearts. We produced TRH overexpression in normal rats by injecting into their left ventricular wall a plasmid driving expression of the preproTRH gene (PCMV-TRH). TRH content and expression of preproTRH, collagen type III, brain natriuretic peptide, β-myosin heavy chain, Bax-to-Bcl-2 ratio, and caspase-3 were measured. The overexpression maneuver was a success, as we found a significant increase in both tripeptide and preproTRH mRNA levels in the PCMV-TRH group compared with the control group. Immunohistochemical staining against TRH showed markedly positive brown signals only in the PCMV-TRH group. TRH overexpression induced a significant increase in fibrosis, evident in the increase of collagen type III expression accompanied by a significant increase in extracellular matrix expansion. We found a significant increase in brain natriuretic peptide and β-myosin heavy chain expression (recognized markers of hypertrophy). Moreover, TRH overexpression induced a slight but significant increase in myocyte diameter, indicating the onset of cell hypertrophy. We confirmed the data “in vitro” using primary cardiac cell cultures (fibroblasts and myocytes). In conclusion, these results show that a specific TRH increase in the left ventricle induced structural changes in the normal heart, thus making the cardiac TRH system a promising therapeutic target.
publishDate 2014
dc.date.none.fl_str_mv 2014-10
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/11336/7807
Schuman, Mariano Luis; Peres Diaz, Ludmila Soledad; Landa, Maria Silvina; Toblli, Jorge Eduardo; Cao, Gabriel Fernando; et al.; Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart; American Physiological Society; American Journal Of Physiology-heart And Circulatory Physiology; 307; 11; 10-2014; 1667-1674
0363-6135
url http://hdl.handle.net/11336/7807
identifier_str_mv Schuman, Mariano Luis; Peres Diaz, Ludmila Soledad; Landa, Maria Silvina; Toblli, Jorge Eduardo; Cao, Gabriel Fernando; et al.; Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart; American Physiological Society; American Journal Of Physiology-heart And Circulatory Physiology; 307; 11; 10-2014; 1667-1674
0363-6135
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://ajpheart.physiology.org/content/307/11/H1667.long
info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpheart.00494.2014
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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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