Artículo
Thyrotropin-Releasing Hormone Overexpression induces structural changes of the Left Ventricle in the normal Rat heart
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
Fecha de publicación:
10/2014
Editorial:
American Physiological Society
Revista:
American Journal Of Physiology-heart And Circulatory Physiology
ISSN:
0363-6135
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Trh
,
Fibrosis
,
Heart
,
Rat
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Articulos(IDIM)
Articulos de INST.DE INVEST.MEDICAS
Articulos de INST.DE INVEST.MEDICAS
Articulos(ININCA)
Articulos de INST.DE INVEST.CARDIOLOGICAS (I)
Articulos de INST.DE INVEST.CARDIOLOGICAS (I)
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
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
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