RT Journal Article T1 Mitochondrial Oxidative Stress Induces Cardiac Fibrosis in Obese Rats through Modulation of Transthyretin A1 Martínez Martínez, Ernesto A1 Fernández-Irigoyen, Joaquín A1 Santamaría, Enrique A1 Nieto, María Luisa A1 Bravo San Pedro, José Manuel A1 Cachofeiro Ramos, María Victoria AB A proteomic approach was used to characterize potential mediators involved in theimprovement in cardiac fibrosis observed with the administration of the mitochondrial antioxidantMitoQ in obese rats. Male Wistar rats were fed a standard diet (3.5% fat; CT) or a high-fat diet (35% fat;HFD) and treated with vehicle or MitoQ (200 µM) in drinking water for 7 weeks. Obesity modulatedthe expression of 33 proteins as compared with controls of the more than 1000 proteins identified.These include proteins related to endoplasmic reticulum (ER) stress and oxidative stress. Proteomicanalyses revealed that HFD animals presented with an increase in cardiac transthyretin (TTR) proteinlevels, an effect that was prevented by MitoQ treatment in obese animals. This was confirmed byplasma levels, which were associated with those of cardiac levels of both binding immunoglobulinprotein (BiP), a marker of ER stress, and fibrosis. TTR stimulated collagen I production and BiP incardiac fibroblasts. This upregulation was prevented by the presence of MitoQ. In summary, theresults suggest a role of TTR in cardiac fibrosis development associated with obesity and the beneficialeffects of treatment with mitochondrial antioxidants. PB MDPI SN 1422-0067 YR 2022 FD 2022-07-22 LK https://hdl.handle.net/20.500.14352/115423 UL https://hdl.handle.net/20.500.14352/115423 LA eng NO Martínez-Martínez E, Fernández-Irigoyen J, Santamaría E, Nieto ML, Bravo-San Pedro JM, Cachofeiro V. Oxidative Stress Induces Cardiac Fibrosis in Obese Rats through Modulation of Transthyretin.Int J Mol Sci. 2022 Jul 22;23(15):8080. NO ISCIII DS Docta Complutense RD 8 abr 2025