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

doi:10.1016/j.jacbts.2020.11.002

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

Medicine - Cardiology Division

Research output: Contribution to journal › Article › peer-review

27 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 language	English (US)
Pages (from-to)	42-52
Number of pages	11
Journal	JACC: Basic to Translational Science
Volume	6
Issue number	1
DOIs	https://doi.org/10.1016/j.jacbts.2020.11.002
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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

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.",

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

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: {\textcopyright} 2021 The Authors",

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doi = "10.1016/j.jacbts.2020.11.002",

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AU - Liu, Hong

AU - Zhao, Yang

AU - Xie, An

AU - Kim, Tae Yun

AU - Terentyeva, Radmila

AU - Liu, Man

AU - Shi, Guangbin

AU - Feng, Feng

AU - Choi, Bum Rak

AU - Terentyev, Dmitry

AU - Hamilton, Shanna

AU - Dudley, Samuel C.

N1 - 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

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

KW - calcium handling

KW - inflammation

KW - mitochondria

KW - oxidation

KW - sudden cardiac death

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

Abstract

Bibliographical note

Keywords

UN SDGs

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