RESUMO
BACKGROUND: Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was designed to evaluate the potential role of DUOX1 in heart failure. MATERIALS AND METHODS: AC16 cells were treated with 2 µmol/L of doxorubicin (DOX) for 12, 24, and 48 h to construct a heart failure model. DUOX1 overexpression and silencing in AC16 cell were established. DUOX1 expression was detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pyroptosis and reactive oxygen species (ROS) production were measured by flow cytometry. RESULTS: Increased DUOX1 expression levels were observed after DOX treatment for 24 h in AC16 cells. DUOX1 silencing inhibited DOX-induced pyroptosis and ROS production. The release of IL-1ß, IL-18, and lactate dehydrogenase (LDH), and expression levels of pyroptosis-related proteins were also decreased. DUOX1 overexpression increased pyroptosis, ROS production, IL-1ß, IL-18, and LDH release, and pyroptosis-related protein expression. N-acetyl-cysteine (NAC) significantly reversed DUOX1-induced pyroptosis, ROS, and related factors. CONCLUSION: These results suggest that DUOX1-derived genotoxicity could promote heart failure development. In the process, oxidative stress and pyroptosis may be involved in the regulation of DUOX1 in heart failure.
Assuntos
Caspase 1 , Doxorrubicina , Oxidases Duais , Insuficiência Cardíaca , Estresse Oxidativo , Piroptose , Espécies Reativas de Oxigênio , Regulação para Cima , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Oxidases Duais/metabolismo , Oxidases Duais/genética , Espécies Reativas de Oxigênio/metabolismo , Humanos , Doxorrubicina/farmacologia , Caspase 1/metabolismo , Linhagem Celular , Interleucina-18/metabolismo , Interleucina-1beta/metabolismoRESUMO
Electrocardiographic characteristics of Wellens syndrome (WS) consist of deeply inverted T waves or biphasic T waves in anterior precordial leads. Studies have shown that patients with WS have critical stenosis or complete obstruction of the proximal left anterior descending coronary artery (LAD) and high risk for the development of extensive anterior myocardial infarction. Here, we reported a case presenting with WS and with a small plaque in the proximal LAD and slow flow in the LAD other than significant stenosis of the proximal LAD detected by coronary angiography. The mechanisms for WS of our case are discussed.