INVESTIGADORES
GARCIA Silvia Ines
artículos
Título:
Thyrotropin-releasing hormone overexpression induces structural changes
Autor/es:
SCHUMAN, MARIANO LUIS; PERES DIAZ LUDMILA; LANDA, MARIA SILVINA; TOBLLI, J; CAO, GABRIEL; ALVAREZ, AZUCENA LAURA; FINKIELMAN, SAMUEL; PIROLA, CARLOS JOSE; GARCIA , SILVIA INES
Revista:
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Editorial:
AMER PHYSIOLOGICAL SOC
Referencias:
Lugar: Philadelphia; Año: 2014
ISSN:
0363-6135
Resumen:
Schuman ML, Peres Diaz LS, Landa MS, Toblli JE, Cao G,
Alvarez AL, Finkielman S, Pirola CJ, García SI. Thyrotropinreleasing
hormone overexpression induces structural changes of the
left ventricle in the normal rat heart. Am J Physiol Heart Circ
Physiol 307: H000?H000, 2014. First published October 3, 2014;
doi:10.1152/ajpheart.00494.2014.?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, -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 -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.Thyrotropinreleasing
hormone overexpression induces structural changes of the
left ventricle in the normal rat heart. Am J Physiol Heart Circ
Physiol 307: H000?H000, 2014. First published October 3, 2014;
doi:10.1152/ajpheart.00494.2014.?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, -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 -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.Am J Physiol Heart Circ
Physiol 307: H000?H000, 2014. First published October 3, 2014;
doi:10.1152/ajpheart.00494.2014.?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, -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 -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.307: H000?H000, 2014. First published October 3, 2014;
doi:10.1152/ajpheart.00494.2014.?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, -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 -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.