2026-04-14T05:06:30Zhttps://recercat.cat/oai/request

oai:recercat.cat:10256/217592024-05-21T10:38:32Zcom_2072_452955com_2072_2054col_2072_452960col_2072_453079

2024-05-21T10:38:32Z urn:hdl:10256/21759 miR-16-5p Suppression Protects Human Cardiomyocytes against Endoplasmic Reticulum and Oxidative Stress-Induced Injury Toro, Rocío Perez-Serra, Alexandra Mangas, Alipio Campuzano Larrea, Oscar Sarquella Brugada, Geòrgia Quezada-Feijoo, Maribel Ramos, Mónica Alcalá, Martin Carrera, Esther García-Padilla, Carlos Franco, Diego Bonet, Fernando Estrès del reticle endoplasmàtic Endoplasmic Reticulum Stress Malaltia coronària Coronary heart disease Espècies reactives de l'oxigen Reactive Oxygen Species Sistema cardiovascular -- Malalties Cardiovascular system -- Diseases Oxidative stress, defined as the excess production of reactive oxygen species (ROS) relative to antioxidant defense, plays a significant role in the development of cardiovascular diseases. Endo-plasmic reticulum (ER) stress has emerged as an important source of ROS and its modulation could be cardioprotective. Previously, we demonstrated that miR-16-5p is enriched in the plasma of ischemic dilated cardiomyopathy (ICM) patients and promotes ER stress-induced apoptosis in cardiomyocytes in vitro. Here, we hypothesize that miR-16-5p might contribute to oxidative stress through ER stress induction and that targeting miR-16-5p may exert a cardioprotective role in ER stress-mediated cardiac injury. Analysis of oxidative markers in the plasma of ICM patients demonstrates that oxida-tive stress is associated with ICM. Moreover, we confirm that miR-16-5p overexpression promotes oxidative stress in AC16 cardiomyoblasts. We also find that, in response to tunicamycin-induced ER stress, miR-16-5p suppression decreases apoptosis, inflammation and cardiac damage via activating the ATF6-mediated cytoprotective pathway. Finally, ATF6 is identified as a direct target gene of miR-16-5p by dual-luciferase reporter assays. Our results indicate that miR-16-5p promotes ER stress and oxidative stress in cardiac cells through regulating ATF6, suggesting that the inhibition of miR-16-5p has potential as a therapeutic approach to protect the heart against ER and oxidative stress-induced injury This work was supported by grants in the framework of the European Regional Development Fund (ERDF) Integrated Territorial Initiative (ITI PI0048-2017 and ITI0033_2019), a clinical research grant from the Spanish Society of Cardiology for Basic Research in cardiology (PI0012_2019), Plan Propio de INIBICA (PI-INBICA 2019-13) 2024-05-21T10:38:32Z 2024-05-21T10:38:32Z 2022-01-18 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion peer-reviewed http://hdl.handle.net/10256/21759 info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms23031036 info:eu-repo/semantics/altIdentifier/issn/1661-6596 info:eu-repo/semantics/altIdentifier/eissn/1422-0067 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess MDPI (Multidisciplinary Digital Publishing Institute) International Journal of Molecular Sciences, 2022, vol. 23, núm. 3, p. 1036 Articles publicats (D-CM)