Specialized pro-resolving mediators prevents cardiac dysfunction by modulating Ca2+ handling and NRF2 axis

Trabajo presentado en el ESC Congress 2021 - The Digital Experience, celebrado en modalidad virtual el 27 de agosto de 2021

Specialized proresolving mediators protect against experimental autoimmune myocarditis by modulating Ca2+ handling and NRF2 activation

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)

Translocation of phosphatidate phosphohydrolase from the cytosol to microsomal membranes in thioacetamide-induced liver tumours in rats

The translocation of phosphatidate phosphohydrolase induced by oleate was higher (two-fold) in liver homogenates obtained from long-term thioacetamide-treated rats than from control rats. These differences between thioacetamide-treated and control livers were noticeably higher (four-fold) in the presence of physiological concentrations of salt (0.15 M KCl). In homogenates from control rats, there was a lack of response when physiological concentrations of the salt were present. The enhanced response to translocate phosphatidate phosphohydrolase activity in liver homogenates from thioacetamide-treated rats was due to an increased binding ability of microsomal membranes.The work was supported by CSIC ID 816.Peer Reviewe

2-deoxy-2[F-18]fluoro-D-mannose positron emission tomography imaging in atherosclerosis

Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2[F-18]fluoro-D-glucose ([F-18]FDG) has been proposed for identification of patients at higher risk for acute vascular events. Because mannose is an isomer of glucose that is taken up by macrophages through glucose transporters and because mannose receptors are expressed on a subset of the macrophage population in high-risk plaques, we applied F-18-labeled mannose (2-deoxy-2[F-18]fluoro-D-mannose, [F-18]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [F-18]FDM and [F-18]FDG in atherosclerotic lesions in a rabbit model; [F-18]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[C-14]carbon-D-glucose ([C-14]2DG) support at least 35% higher [F-18]FDM uptake by macrophages in cell experiments. We also demonstrate that FDM restricts binding of anti mannose receptor antibody to macrophages by approximately 35% and that mannose receptor targeting may provide an additional avenue for imaging of plaque inflammation