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La autofagia Beclin-1-dependiente protege el corazón durante la sepsis
Yuxiao Sun1, Xiao Yao1, Qing-Jun Zhang2
1Departments of Surgery (Y.S., X.Y., D.C., S.E.W., J.P.M., Q.S.Z.), University of Texas Southwestern Medical Center, Dallas.
Circulation
|June 2, 2018
Resumen
La autofagia dependiente de Beclin-1 protege el corazón durante la sepsis. La activación de la señalización de Beclin-1 mejoró la función cardíaca y redujo la inflamación, lo que sugiere una estrategia terapéutica potencial para la disfunción cardíaca inducida por la sepsis.
Área de la Ciencia:
- Biología cardiovascular
- Biología celular
- La medicina molecular
Sus antecedentes:
- La disfunción cardíaca inducida por sepsis es un componente crítico de la insuficiencia multiorgánica.
- El papel preciso de la autofagia cardíaca en la patogénesis de la sepsis sigue sin estar claro.
- Las terapias dirigidas a la autofagia para la sepsis están actualmente subdesarrolladas.
Objetivo del estudio:
- Para investigar la autofagia dependiente de Beclin-1 en el corazón durante la sepsis.
- Para explorar el potencial terapéutico de dirigirse a la vía de la autofagia en la sepsis.
Principales métodos:
- Se utilizó un modelo de sepsis inducida por lipopolisacáridos (LPS) en ratones.
- Se emplearon la sobreexpresión y la haplosufficiencia de Beclin 1 específicas para el corazón.
- Se utilizó un péptido Tat-Beclin-1 permeable a las células para activar la autofagia.
Principales resultados:
- El LPS modula la autofagia de manera dependiente de la dosis, con dosis altas que activan el objetivo de la rapamicina en mamíferos (mTOR).
- La sobreexpresión de Beclin-1 mejoró la función cardíaca, suprimió la mTOR y redujo la inflamación y la fibrosis.
- Beclin-1 protegió las mitocondrias, redujo los patrones moleculares asociados al peligro y promovió la mitofagia.
- La administración de péptido Tat-Beclin-1 mejoró la función cardíaca y atenuó la inflamación en ratones con LPS.
Conclusiones:
- Beclin-1 juega un papel protector en el corazón durante la sepsis.
- La inducción dirigida de la señalización de Beclin-1 representa una vía terapéutica prometedora para la disfunción cardíaca relacionada con la sepsis.
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