1. Specialized Proresolving Mediators Protect Against Experimental Autoimmune Myocarditis by Modulating Ca2+ Handling and NRF2 Activation
- Author
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Almudena Val-Blasco, Patricia Prieto, Rafael Iñigo Jaén, Marta Gil-Fernández, Marta Pajares, Nieves Domenech, Verónica Terrón, María Tamayo, Inmaculada Jorge, Jesús Vázquez, Andrea Bueno-Sen, María Teresa Vallejo-Cremades, Jorge Pombo-Otero, Sergio Sanchez-García, Gema Ruiz-Hurtado, Ana María Gómez, Carlos Zaragoza, María Generosa Crespo-Leiro, Eduardo López-Collazo, Antonio Cuadrado, Carmen Delgado, Lisardo Boscá, María Fernández-Velasco, Ministerio de Economía y Competitividad (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Instituto de Salud Carlos III, Sociedad Española de Cardiología, Unión Europea. Fondo Social Europeo (ESF/FSE), Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares), Ministerio de Ciencia, Innovación y Universidades (España), Fundación La Caixa, Agencia Estatal de Investigación (España), and Fundación 'la Caixa'
- Subjects
Myocarditis ,Pro-resolving mediators ,Calcium handling ,SERCA2A ,Cardiology and Cardiovascular Medicine ,NRF2 - Abstract
Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulum–adenosine triphosphatase 2A down-regulation and Ca2+ mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis., This work was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (SAF-2017-84777R), Instituto de Salud Carlos III (ISCIII) (PI17/01093, PI17/01344, and PI20/01482), Sociedad Española de Cardiología, Proyecto Traslacional 2019 and Asociación del Ritmo Cardiaco (SEC, España), Proyecto Asociación Insuficiencia Cardiaca (Trasplante Cardiaco) 2020, Fondo Europeo de Desarrollo Regional, Fondo Social Europeo, and CIBERCV, a network funded by ISCIII, Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00), Ministerio de Economía, Industria y Competitividad/Agencia Estatal de Investigación 10.13039/501100011033 PID2020-113238RB-I00, PID2019-105600RB-I00, the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3 [PT17/0019/0003-ISCIII-SGEFI/ERDF, ProteoRed]), and “la Caixa” Foundation (project code HR17-00247). The Centro Nacional de Investigaciones Cardiovasculares is supported by the ISCIII, the Ministerio de Ciencia, Innovación y Universidades. Dr Ruiz-Hurtado is Miguel Servet I researcher of ISCIII (CP15/00129 Carlos III Health Institute). Dr Tamayo and R.I. Jaén, and M. Gil-Fernández were or currently are PhD students funded by the Formación de Profesorado Universitario program of the Spanish Ministry of Science, Innovation and Universities (FPU17/06135; FPU16/00827, FPU1901973).
- Published
- 2022