RT Journal Article T1 The Interplay of Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress in Cardiovascular Fibrosis in Obese Rats A1 Souza Neto, Francisco V. A1 Jiménez González, Sara A1 Delgado Valero, Beatriz A1 Jurado López, Raquel A1 Genty, Marie A1 Romero Miranda, Ana A1 Rodríguez, Cristina A1 Nieto, María Luisa A1 Martínez Martínez, Ernesto A1 Cachofeiro Ramos, María Victoria AB We have evaluated the role of mitochondrial oxidative stress and its association with endoplasmic reticulum (ER) stress activation in the progression of obesity-related cardiovascular fibrosis. MitoQ (200 µM) was orally administered for 7 weeks to male Wistar rats that were fed a high-fat diet (HFD, 35% fat) or a control diet (CT, 3.5% fat). Obese animals presented cardiovascular fibrosis accompanied by increased levels of extracellular matrix proteins and profibrotic mediators. These alterations were associated with ER stress activation characterized by enhanced levels (in heart and aorta vs. CT group, respectively) of immunoglobulin binding protein (BiP; 2.1-and 2.6-fold, respectively), protein disulfide-isomerase A6 (PDIA6; 1.9-fold) and CCAAT-enhancer-binding homologous protein (CHOP; 1.5- and 1.8-fold, respectively). MitoQ treatment was able to prevent (p < 0.05) these modifications at cardiac and aortic levels. MitoQ (5 nM) and the ER stress inhibitor, 4-phenyl butyric acid (4 µM), were able to block the prooxidant and profibrotic effects of angiotensin II (Ang II, 10−6 M) in cardiac and vascular cells. Therefore, the data show a crosstalk between mitochondrial oxidative stress and ER stress activation, which mediates the development of cardiovascular fibrosis in the context of obesity and in which Ang II can play a relevant role. PB MPDI SN 2076-3921 YR 2021 FD 2021-08-11 LK https://hdl.handle.net/20.500.14352/4872 UL https://hdl.handle.net/20.500.14352/4872 LA eng NO Souza Neto, F. V., Jiménez González, S., Delgado Valero, B. et al. «The Interplay of Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress in Cardiovascular Fibrosis in Obese Rats». Antioxidants, vol. 10, n.o 8, agosto de 2021, p. 1274. DOI.org (Crossref), https://doi.org/10.3390/antiox10081274. NO Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional NO Universidad Complutense de Madrid/Banco de Santander NO Instituto de Salud Carlos III NO Comunidad de Madrid DS Docta Complutense RD 6 abr 2025