MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension.

Pulmonary hypertension (PH) can affect both pulmonary arterial tree and cardiac function, often leading to right heart failure and death. Despite the urgency, the lack of understanding has limited the development of effective cardiac therapeutic strategies. Our research reveals that MCJ modulates mi...

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Detalles Bibliográficos
Autores: Santamans, Ayelén M, Cicuéndez, Beatriz, Mora, Alfonso, Villalba-Orero, María, Rajlic, Sanela, Crespo, María, Vo, Paula, Jerome, Madison, Macías, Álvaro, López, Juan Antonio, Leiva, Magdalena, Rocha, Susana F, León, Marta, Rodríguez, Elena, Leiva, Luis, Pintor Chocano, Aránzazu, García Lunar, Inés, García-Álvarez, Ana, Hernansanz-Agustín, Pablo, Peinado, Víctor I, Barberá, Joan Albert, Ibáñez, Borja, Vázquez, Jesús, Spinelli, Jessica B, Daiber, Andreas, Oliver, Eduardo, Sabio, Guadalupe
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/18917
Acceso en línea:http://hdl.handle.net/20.500.12105/18917
Access Level:acceso abierto
Palabra clave:Hypertension, Pulmonary
Animals
Humans
Mice
Hypoxia
Lung
Myocardium
Pulmonary Artery
Swine
Descripción
Sumario:Pulmonary hypertension (PH) can affect both pulmonary arterial tree and cardiac function, often leading to right heart failure and death. Despite the urgency, the lack of understanding has limited the development of effective cardiac therapeutic strategies. Our research reveals that MCJ modulates mitochondrial response to chronic hypoxia. MCJ levels elevate under hypoxic conditions, as in lungs of patients affected by COPD, mice exposed to hypoxia, and myocardium from pigs subjected to right ventricular (RV) overload. The absence of MCJ preserves RV function, safeguarding against both cardiac and lung remodeling induced by chronic hypoxia. Cardiac-specific silencing is enough to protect against cardiac dysfunction despite the adverse pulmonary remodeling. Mechanistically, the absence of MCJ triggers a protective preconditioning state mediated by the ROS/mTOR/HIF-1α axis. As a result, it preserves RV systolic function following hypoxia exposure. These discoveries provide a potential avenue to alleviate chronic hypoxia-induced PH, highlighting MCJ as a promising target against this condition.

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