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Isolation, Culture and Transduction of Adult Mouse Cardiomyocytes

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El malonato promueve la proliferación de los cardiomiocitos adultos y la regeneración del corazón

Jiyoung Bae¹, Rebecca J Salamon¹, Emma B Brandt¹

¹Department of Cell and Regenerative Biology (J.B., R.J.S., E.B.B., W.G.P., Z.Z., A.I.M.), University of Wisconsin-Madison School of Medicine and Public Health.

|March 5, 2021

Resumen

La inhibición de la succinato deshidrogenasa (SDH) con malonato promueve la regeneración del corazón en ratones adultos al aumentar la proliferación y revascularización de los cardiomiocitos, ofreciendo una nueva estrategia terapéutica para la insuficiencia cardíaca.

Área de la Ciencia:

Biología cardiovascular
La reprogramación metabólica
La Medicina Regenerativa

Sus antecedentes:

Los cardiomiocitos neonatales cambian el metabolismo, aumentando las especies reactivas de oxígeno y el daño al ADN, lo que lleva a la salida del ciclo celular y a la pérdida de la capacidad de regeneración.
Los mecanismos que regulan este cambio metabólico y la producción de especies reactivas de oxígeno son poco conocidos.
Las mutaciones de la sucinato deshidrogenasa (SDH) están vinculadas a cambios metabólicos en el cáncer, lo que sugiere su papel en el metabolismo celular y potencialmente en la regeneración cardíaca.

Objetivo del estudio:

Investigar el papel de la inhibición de succinato y SDH en la regulación de la actividad del ciclo celular cardiomiocítico postnatal.
Explorar el potencial de la inhibición de SDH para promover la regeneración cardíaca.

Principales métodos:

Investigó los efectos de la inyección de succinato y la inhibición de SDH utilizando malonato en ratones neonatales, juveniles y adultos.
Tratamiento con malonato administrado después de un infarto de miocardio en ratones adultos.
Se realizó un análisis de metabolitos para evaluar los cambios metabólicos cardíacos.

Principales resultados:

La inyección de succinato inhibió la proliferación y regeneración de los cardiomiocitos neonatales.
Inhibición de la SDH con proliferación y regeneración extendida de cardiomiocitos en ratones juveniles.
El tratamiento con malonato en ratones adultos después de un infarto de miocardio indujo una regeneración cardíaca robusta, caracterizada por la proliferación y revascularización de los cardiomiocitos.

Conclusiones:

La inhibición de SDH a través del malonato promueve la proliferación de cardiomiocitos adultos, la revascularización y la regeneración del corazón a través de la reprogramación metabólica.
Estos hallazgos sugieren un nuevo enfoque terapéutico para el tratamiento de la insuficiencia cardíaca humana.

Palabras clave:

ciclo celular el metabolismo Infarto de miocardio regeneración succinato deshidrogenasa

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