Interleukin-1β, Oxidative Stress, and Abnormal Calcium Handling Mediate Diabetic Arrhythmic Risk

Diabetes mellitus (DM) is associated with increased arrhythmia. Type 2 DM (T2DM) mice showed prolonged QT interval and increased ventricular arrhythmic inducibility, accompanied by elevated cardiac interleukin (IL)-1β, increased mitochondrial reactive oxygen species (mitoROS), and oxidation of the s...

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Detalles Bibliográficos
Autores principales: Liu, Hong, Zhao, Yang, Xie, An, Kim, Tae-Yun, Terentyeva, Radmila, Liu, Man, Shi, Guangbin, Feng, Feng, Choi, Bum-Rak, Terentyev, Dmitry, Hamilton, Shanna, Dudley, Samuel C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Preclinical Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838050/
https://www.ncbi.nlm.nih.gov/pubmed/33532665
http://dx.doi.org/10.1016/j.jacbts.2020.11.002
Descripción
Sumario:Diabetes mellitus (DM) is associated with increased arrhythmia. Type 2 DM (T2DM) mice showed prolonged QT interval and increased ventricular arrhythmic inducibility, accompanied by elevated cardiac interleukin (IL)-1β, increased mitochondrial reactive oxygen species (mitoROS), and oxidation of the sarcoplasmic reticulum (SR) Ca(2+) release channel (ryanodine receptor 2 [RyR2]). Inhibiting IL-1β and mitoROS reduced RyR2 oxidation and the ventricular arrhythmia in DM. Inhibiting SR Ca2(+) leak by stabilizing the oxidized RyR2 channel reversed the diabetic arrhythmic risk. In conclusion, cardiac IL-1β mediated the DM-associated arrhythmia through mitoROS generation that enhances SR Ca(2+) leak. The mechanistic link between inflammation and arrhythmias provides new therapeutic options.

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