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La vía de señalización mediada por G13 es necesaria para la remodelación cardíaca inducida por sobrecarga de presión

Mikito Takefuji¹, Angela Wirth, Martina Lukasova

¹Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.

|September 14, 2012

Resumen

La familia de proteínas G12/13, específicamente Gα13, es crucial en la remodelación cardíaca inducida por sobrecarga de presión y la progresión a la insuficiencia cardíaca. La inactivación de Gα(13) protege contra la hipertrofia cardíaca y la fibrosis.

Área de la Ciencia:

Biología Cardiovascular Biología Cardiovascular
Cardiología Molecular Cardiología Molecular
La señalización de la proteína G.

Sus antecedentes:

La remodelación cardíaca es un factor clave en la patogénesis de la insuficiencia cardíaca, impulsada por el estrés mecánico.
Los factores humorísticos como la angiotensina II y la endotelina-1 promueven la hipertrofia cardíaca y la fibrosis a través de la señalización G.
El papel de la familia de proteínas G ((12/13) en la remodelación cardíaca sigue siendo en gran medida desconocido.

Objetivo del estudio:

Investigar el papel de la familia de proteínas G 12/13 en la remodelación cardíaca inducida por sobrecarga de presión.
Determinar la contribución específica de Gα(13) a la hipertrofia cardíaca, la fibrosis y la progresión de la insuficiencia cardíaca.

Principales métodos:

Utilizó knockdown mediado por siRNA in vitro y inactivación condicional de genes in vivo.
Centrado en la inactividad inducible específica de los cardiomiocitos de Gα 13).
Evaluó la función cardíaca, la hipertrofia, la fibrosis y las vías de señalización molecular.

Principales resultados:

La inactivación inducible específica de los cardiomiocitos de Gα ((13) no afectó la función cardíaca basal.
La inactivación de Gα(q/13) protegió a los ratones de hipertrofia y fibrosis inducidas por sobrecarga de presión, comparable a la inactivación de Gα(q/11).
La inactivación de Gα ((13) impidió el desarrollo de insuficiencia cardíaca durante hasta 1 año después de la sobrecarga.
Gα(13) controla la expresión inducida por agonistas de genes específicos de la hipertrofia a través de RhoA y los factores de transcripción relacionados con la miocardina.

Conclusiones:

La familia de proteínas G ((12/13) está involucrada de manera central en la remodelación cardíaca inducida por sobrecarga de presión.
La señalización juega un papel crítico en la transición de la remodelación cardíaca a la insuficiencia cardíaca.

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