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La activación del proteasoma cardíaco durante la sobrecarga de presión promueve la hipertrofia ventricular
Christophe Depre1, Qian Wang, Lin Yan
1Department of Cell Biology & Molecular Medicine, UMDNJ, Newark, NJ 07103, USA.
Circulation
|October 18, 2006
Resumen
La sobrecarga crónica de presión activa el sistema proteasómico en el corazón, que es esencial para el desarrollo de la hipertrofia ventricular izquierda (LVH). Esta activación del proteasoma es específica para el subendocardio y se requiere para el establecimiento de LVH.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- Biología Molecular Biología Molecular
- La proteostasis es la proteostasis.
Sus antecedentes:
- La adaptación cardíaca a la sobrecarga hemodinámica depende de la rotación de proteínas.
- La hipertrofia ventricular izquierda (LVH) implica adaptaciones moleculares complejas.
- Se investigó el papel del sistema proteasómico en el desarrollo de LVH.
Objetivo del estudio:
- Para determinar si la LVH crónica activa el sistema proteasómico, particularmente en el subendocardio.
- Para investigar si el sistema proteasómico es necesario para el desarrollo de LVH.
Principales métodos:
- Se evaluó la expresión y actividad de genes y proteínas de las subunidades del proteasoma en modelos caninos y de ratón de LVH.
- Utilizó bandas aórticas para inducir LVH crónica.
- Empleó el inhibidor del proteasoma epoxomicina en un modelo de ratón.
Principales resultados:
- La expresión y la actividad del proteasoma aumentaron significativamente en el subendocardio de los corazones de LVH en comparación con los controles.
- Estos cambios fueron específicos para el subendocardio y no se observaron en otros tejidos cardíacos o periféricos.
- La inhibición del proteasoma en ratones impidió completamente el desarrollo de LVH.
Conclusiones:
- El aumento de la expresión y la actividad del proteasoma en el subendocardio son características clave de la sobrecarga crónica de presión.
- El sistema proteasómico es un requisito crítico para el desarrollo de LVH.
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