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

Overview

Journal JACC Basic Transl Sci

Date 2021 Feb 3

PMID 33532665

Citations 23

Authors

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 Jr

Affiliations

Soon will be listed here.

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) Ca 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 leak. The mechanistic link between inflammation and arrhythmias provides new therapeutic options.

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