Abstract
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) Ca2+ 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 Ca2+ leak. The mechanistic link between inflammation and arrhythmias provides new therapeutic options.
Original language | English (US) |
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Pages (from-to) | 42-52 |
Number of pages | 11 |
Journal | JACC: Basic to Translational Science |
Volume | 6 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2021 |
Bibliographical note
Publisher Copyright:© 2021 The Authors
Keywords
- calcium handling
- inflammation
- mitochondria
- oxidation
- sudden cardiac death