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Las estatinas activan la proteína quinasa activada por AMP in vitro e in vivo
Wei Sun1, Tzong-Shyuan Lee, Minjia Zhu
1Division of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521-0121, USA.
Circulation
|November 23, 2006
Resumen
Las estatinas activan la proteína quinasa activada por AMP (AMPK), mejorando la actividad de la endotelio óxido nítrico sintetasa (eNOS). Esta activación de la AMPK explica los beneficios cardiovasculares de las estatinas al aumentar la producción de óxido nítrico y la angiogénesis.
Área de la Ciencia:
- Farmacología Cardiovascular Farmacología Cardiovascular
- Biología Molecular Biología Molecular
- El metabolismo celular es el metabolismo celular.
Sus antecedentes:
- Las estatinas ofrecen beneficios cardiovasculares, en parte al aumentar la biodisponibilidad del óxido nítrico (NO).
- La proteína quinasa activada por AMP (AMPK) es crucial para la energía celular y el metabolismo.
- La relación entre las estatinas, la activación de AMPK y la producción de NO a través de la NO sintetasa endotelial (eNOS) requiere aclaración.
Objetivo del estudio:
- Para investigar si las estatinas activan AMPK.
- Para determinar si la AMPK activada modula la producción de NO y la angiogénesis a través de eNOS.
- Para explorar el mecanismo detrás de los efectos pleiotrópicos cardiovasculares de las estatinas.
Principales métodos:
- Las células endotelial de la vena umbilical humana fueron tratadas con atorvastatina.
- Los ensayos de Western blotting y SAMS evaluaron la AMPK y su fosforilación objetivo.
- Los estudios de inhibición utilizaron AMPK dominante-negativo (Ad-AMPK-DN) y el compuesto C.
- Los estudios in vivo incluyeron la administración de atorvastatina a ratones.
Principales resultados:
- La atorvastatina aumentó la fosforilación y la actividad de la AMPK en las células endoteliales de una manera dependiente de la dosis y el tiempo.
- La activación de AMPK condujo a la fosforilación de la acetil-CoA carboxilasa y eNOS.
- La inhibición de la AMPK bloqueaba la producción de NO inducida por la atorvastatina, la acumulación de GMPc y la angiogénesis.
- In vivo, la atorvastatina aumentó la fosforilación de AMPK, ACC y eNOS en la aorta y el miocardio del ratón.
Conclusiones:
- Las estatinas activan rápidamente la AMPK a través de la fosforilación de Thr-172, tanto in vitro como in vivo.
- Esta activación estimula eNOS, lo que lleva a un aumento de la producción de NO.
- La activación de AMPK por las estatinas ofrece un nuevo mecanismo para sus efectos protectores cardiovasculares.
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