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La expresión, activación y función de la calcineurina en la hipertrofia por sobrecarga de presión cardíaca
H W Lim1, L J De Windt, L Steinberg
1Department of Pediatrics, Children's Hospital Medical Center, University of Cincinnati, Ohio, USA.
Circulation
|May 24, 2000
Resumen
La actividad de la calcineurina aumenta con la carga cardíaca, lo que contribuye a la hipertrofia cardíaca. La inhibición de la calcineurina con ciclosporina A (CsA) atenuó y revirtió parcialmente esta hipertrofia en ratas.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- Cardiología Molecular Cardiología Molecular
- Fisiología Fisiología Fisiología.
Sus antecedentes:
- La hipertensión vascular aumenta la carga cardíaca, lo que lleva a la hipertrofia ventricular izquierda y enfermedades del corazón.
- Las vías moleculares que regulan la hipertrofia cardíaca no se comprenden completamente.
- La calcineurina, una fosfatasa sensible al calcio, es un regulador potencial de la hipertrofia cardíaca.
Objetivo del estudio:
- Para investigar el papel de la calcineurina en la hipertrofia cardíaca inducida por sobrecarga de presión.
- Para determinar si la actividad y la expresión de la calcineurina aumentan con la carga cardíaca.
- Para evaluar el efecto de la inhibición de la calcineurina en la hipertrofia cardíaca.
Principales métodos:
- Hipertrofia inducida por sobrecarga de presión en ratas a través de bandas aórticas abdominales.
- Medido la actividad enzimática de la calcineurina y el contenido de proteínas en el tejido cardíaco.
- Utilizó el análisis de Western blot para evaluar la asociación entre la calcineurina y la calmodulina.
- Se administró ciclosporina A (CsA), un inhibidor de la calcineurina, a ratas.
Principales resultados:
- La actividad enzimática de la calcineurina y el contenido de proteínas aumentaron significativamente en respuesta a la hipertrofia por sobrecarga de presión.
- El aumento del contenido de proteína de calcineurina se asoció con un aumento de la unión a la calmodulina.
- La administración de CsA evitó y revirtió parcialmente la hipertrofia cardíaca de una manera dependiente de la dosis.
- El tratamiento con CsA atenuó los marcadores histológicos y moleculares de hipertrofia.
Conclusiones:
- La calcineurina es un regulador clave de la hipertrofia cardíaca inducida por la carga.
- La inhibición de la calcineurina con CsA ofrece una estrategia terapéutica potencial para el manejo de la hipertrofia cardíaca.
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