Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/18917
Title
MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension.
Author(s)
Santamans, Ayelén M | Cicuéndez, Beatriz | Mora, Alfonso CNIC | Villalba-Orero, María | Rajlic, Sanela | Crespo, María | Vo, Paula | Jerome, Madison | Macías, Álvaro | López, Juan Antonio | Leiva, Magdalena CNIC | 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 CNIC | Vázquez, Jesús | Spinelli, Jessica B | Daiber, Andreas | Oliver, Eduardo CNIC | Sabio, Guadalupe CNIC
Date issued
2024-01-19
Citation
Sci Adv. 2024 Jan 19;10(3):eadk6524.
Language
Inglés
Document type
journal article
Abstract
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.
MESH
Hypertension, Pulmonary | Animals | Humans | Mice | Hypoxia | Lung | Myocardium | Pulmonary Artery | Swine
Online version
DOI
Collections