RT Journal Article
T1 MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension
A1 Santamans, Ayelén M.
A1 Cicuéndez, Beatriz
A1 Mora, Alfonso
A1 Rajlic, Sanela
A1 Crespo, María
A1 Vo, Paula
A1 Jerome, Madison
A1 Macías, Álvaro
A1 López, Juan Antonio
A1 Rocha, Susana F.
A1 León, Marta
A1 Rodríguez, Elena
A1 Leiva, Luis
A1 Pintor Chocano, Aránzazu
A1 García Lunar, Inés
A1 García-Álvarez, Ana
A1 Hernansanz-Agustín, Pablo
A1 Peinado, Víctor I.
A1 Barberá, Joan Albert
A1 Ibañez, Borja
A1 Vázquez, Jesús
A1 Spinelli, Jessica B.
A1 Daiber, Andreas
A1 Oliver, Eduardo
A1 Sabio, Guadalupe
A1 Villalba Orero, María
A1 Leiva Arjona, María Magdalena
AB 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.
PB Science Advances
SN 2375-2548
YR 2024
FD 2024-01-19
LK https://hdl.handle.net/20.500.14352/97801
UL https://hdl.handle.net/20.500.14352/97801
LA eng
NO MINECO
NO Comunidad de Madrid
NO Severo Ochoa CNIC
NO Instituto de Salud Carlos III
NO Fundación “La Caixa”
NO Juan de la Cierva Incorporación Grant
NO MICINN
DS Docta Complutense
RD 6 abr 2025