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

Hong Liu, Yang Zhao, An Xie, Tae Yun Kim, Radmila Terentyeva, Man Liu, Guangbin Shi, Feng Feng, Bum Rak Choi, Dmitry Terentyev, Shanna Hamilton, Samuel C. Dudley

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 languageEnglish (US)
Pages (from-to)42-52
Number of pages11
JournalJACC: Basic to Translational Science
Volume6
Issue number1
DOIs
StatePublished - Jan 2021

Bibliographical note

Funding Information:
This work was supported by National Heart Lung and Blood Institute Grant Nos. R01HL134791 and R01HL104025. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2021 The Authors

Keywords

  • calcium handling
  • inflammation
  • mitochondria
  • oxidation
  • sudden cardiac death

PubMed: MeSH publication types

  • Journal Article

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