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dc.contributor.author
Schuman, Mariano Luis
dc.contributor.author
Peres Diaz, Ludmila Soledad
dc.contributor.author
Landa, Maria Silvina
dc.contributor.author
Toblli, Jorge Eduardo
dc.contributor.author
Cao, Gabriel Fernando
dc.contributor.author
Alvarez, Azucena L.
dc.contributor.author
Finkielman, Samuel
dc.contributor.author
Pirola, Carlos Jose
dc.contributor.author
Garcia, Silvia Ines
dc.date.available
2016-10-26T21:20:07Z
dc.date.issued
2014-10
dc.identifier.citation
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
dc.identifier.issn
0363-6135
dc.identifier.uri
http://hdl.handle.net/11336/7807
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Physiological Society
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Trh
dc.subject
Fibrosis
dc.subject
Heart
dc.subject
Rat
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-08-30T17:10:50Z
dc.journal.volume
307
dc.journal.number
11
dc.journal.pagination
1667-1674
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Schuman, Mariano Luis. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
dc.description.fil
Fil: Peres Diaz, Ludmila Soledad. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
dc.description.fil
Fil: Landa, Maria Silvina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
dc.description.fil
Fil: Toblli, Jorge Eduardo. Hospital Aleman; Argentina
dc.description.fil
Fil: Cao, Gabriel Fernando. Hospital Aleman; Argentina
dc.description.fil
Fil: Alvarez, Azucena L.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
dc.description.fil
Fil: Finkielman, Samuel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
dc.description.fil
Fil: Pirola, Carlos Jose. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
dc.description.fil
Fil: Garcia, Silvia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina
dc.journal.title
American Journal Of Physiology-heart And Circulatory Physiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://ajpheart.physiology.org/content/307/11/H1667.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1152/ajpheart.00494.2014


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