Título

The role of the mitochondrial calcium uniporter in the process of arrhythmogenesis in a murine model of acute catecholamine overload

Autor

FELIPE DE JESUS SALAZAR RAMIREZ

Nivel de Acceso

Acceso Abierto

Resumen o descripción

https://orcid.org/0000-0003-4731-3293

Sudden cardiac death by fulminant ventricular arrhythmias remains a concern in population with cardiac risk. Recently, the mitochondrion has been implied to be a central player in Ca2+ mishandling, with its dysfunction leading up to arrhythmogenesis. A possible starting event that could lead to most changes seen in cardiac disfunction is mitochondrial Ca2+ overload. The following research study focuses on demonstrating the effects of mitochondrial Ca2+ influx inhibition in arrhythmogenesis. A murine model of acute catecholamine (isoproterenol) overload was treated previously with mitochondrial Ca2+ transport inhibitor Ru360. Ru360 treated mice showed a complete abolishment of ventricular tachycardia and ventricular fibrillation. To characterize the possible mechanisms of action, heart mitochondria were isolated and mitochondrial function was assessed. Mitochondrial Ca2+ transport inhibition preserved mitochondrial function and membrane integrity as demonstrated by a higher respiratory control and calcium retention capacity when compared to isoproterenol-treated mice which appears to be caused by a reduced oxidative stress as a trend to preserve reduced thiol groups was shown. Given the positive results obtained in abolishing ventricular arrhythmias by inhibiting mitochondrial Ca2+ transport, it is precise to continue the characterization of the mechanisms by which this therapy exerts its effects. To fully demonstrate its efficacy and characterize its mechanism of action may lead up to a new therapeutic target and therapy that could set the bases to clinical research in the near future.

Maestro en Ciencias Biomédicas

Editor

Instituto Tecnológico y de Estudios Superiores de Monterrey

Fecha de publicación

22 de mayo de 2020

Tipo de publicación

Tesis de maestría

Recurso de información

Formato

application/pdf

Idioma

Inglés

Audiencia

Investigadores

Repositorio Orígen

Repositorio Institucional del Tecnológico de Monterrey

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