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La autofagia Beclin-1-dependiente protege el corazón durante la sepsis

  • 0Departments 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 +

|

2 de junio de 2018

|

2 de junio de 2018

Ver abstracta en PubMed

Resumen

Este resumen es generado por máquina.

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.

Palabras clave:

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