RT Journal Article
T1 Mitochondrial Oxidative Stress Induces Cardiac Fibrosis in Obese Rats through Modulation of Transthyretin
A1 Martínez Martínez, Ernesto
A1 Fernandez Irigoyen, Joaquín
A1 Santamaria, 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 the improvement in cardiac fibrosis observed with the administration of the mitochondrial antioxidant MitoQ 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 modulated the 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. Proteomic analyses revealed that HFD animals presented with an increase in cardiac transthyretin (TTR) protein levels, an effect that was prevented by MitoQ treatment in obese animals. This was confirmed by plasma levels, which were associated with those of cardiac levels of both binding immunoglobulin protein (BiP), a marker of ER stress, and fibrosis. TTR stimulated collagen I production and BiP in cardiac fibroblasts. This upregulation was prevented by the presence of MitoQ. In summary, the results suggest a role of TTR in cardiac fibrosis development associated with obesity and the beneficial effects of treatment with mitochondrial antioxidants.
PB MDPI
SN 1422-0067
YR 2022
FD 2022-07-22
LK https://hdl.handle.net/20.500.14352/72192
UL https://hdl.handle.net/20.500.14352/72192
LA eng
NO Unión Europea
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 13 abr 2025