Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility

Yung Nan Tsai; Ya Wen Hsiao; Shien-Fong Lin; Yi Hsin Chan; Yu Cheng Hsieh; Wei Hua Tang; An Sheng Lee; Yu Ting Huang; Hsing Yuan Li; Tze Fan Chao; Satoshi Higa; Tsu Juey Wu; Shih Lin Chang; Shih Ann Chen

doi:10.3389/fcvm.2021.623510

Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility

Yung Nan Tsai, Ya Wen Hsiao, Shien-Fong Lin, Yi Hsin Chan, Yu Cheng Hsieh, Wei Hua Tang, An Sheng Lee, Yu Ting Huang, Hsing Yuan Li, Tze Fan Chao, Satoshi Higa, Tsu Juey Wu, Shih Lin Chang, Shih Ann Chen^*

^*Corresponding author for this work

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

2 Scopus citations

Abstract

Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Ca_i) handling and VA susceptibility by IL-17. Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Ca_i transient duration (Ca_iTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed. Results: There were longer APD₈₀, Ca_iTD₈₀ and increased thresholds of APD and Ca_iTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na⁺/Ca²⁺ exchanger, phospholamban, and ryanodine receptor Ca²⁺ release channel were upregulated, and the subunit of L-type Ca²⁺ current and sarcoplasmic reticulum Ca²⁺-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group. Conclusions: IL-17 enhanced Ca_iTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.

Original language	English
Article number	623510
Journal	Frontiers in Cardiovascular Medicine
Volume	8
DOIs	https://doi.org/10.3389/fcvm.2021.623510
State	Published - 16 Mar 2021

Keywords

alternans
IL-17
IL-17 neutralizer
the maximum calcium transient
ventricular arrhythmias

Access to Document

10.3389/fcvm.2021.623510

Cite this

Tsai, Y. N., Hsiao, Y. W., Lin, S-F., Chan, Y. H., Hsieh, Y. C., Tang, W. H., Lee, A. S., Huang, Y. T., Li, H. Y., Chao, T. F., Higa, S., Wu, T. J., Chang, S. L., & Chen, S. A. (2021). Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility. Frontiers in Cardiovascular Medicine, 8, Article 623510. https://doi.org/10.3389/fcvm.2021.623510

@article{c6724fe9f10046f1b6db42acee621929,

title = "Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility",

abstract = "Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Cai) handling and VA susceptibility by IL-17. Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Cai transient duration (CaiTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed. Results: There were longer APD80, CaiTD80 and increased thresholds of APD and CaiTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor Ca2+ release channel were upregulated, and the subunit of L-type Ca2+ current and sarcoplasmic reticulum Ca2+-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group. Conclusions: IL-17 enhanced CaiTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.",

keywords = "alternans, IL-17, IL-17 neutralizer, the maximum calcium transient, ventricular arrhythmias",

author = "Tsai, {Yung Nan} and Hsiao, {Ya Wen} and Shien-Fong Lin and Chan, {Yi Hsin} and Hsieh, {Yu Cheng} and Tang, {Wei Hua} and Lee, {An Sheng} and Huang, {Yu Ting} and Li, {Hsing Yuan} and Chao, {Tze Fan} and Satoshi Higa and Wu, {Tsu Juey} and Chang, {Shih Lin} and Chen, {Shih Ann}",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Tsai, Hsiao, Lin, Chan, Hsieh, Tang, Lee, Huang, Li, Chao, Higa, Wu, Chang and Chen.",

year = "2021",

month = mar,

day = "16",

doi = "10.3389/fcvm.2021.623510",

language = "English",

volume = "8",

journal = "Frontiers in Cardiovascular Medicine",

issn = "2297-055X",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility

AU - Tsai, Yung Nan

AU - Hsiao, Ya Wen

AU - Lin, Shien-Fong

AU - Chan, Yi Hsin

AU - Hsieh, Yu Cheng

AU - Tang, Wei Hua

AU - Lee, An Sheng

AU - Huang, Yu Ting

AU - Li, Hsing Yuan

AU - Chao, Tze Fan

AU - Higa, Satoshi

AU - Wu, Tsu Juey

AU - Chang, Shih Lin

AU - Chen, Shih Ann

PY - 2021/3/16

Y1 - 2021/3/16

N2 - Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Cai) handling and VA susceptibility by IL-17. Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Cai transient duration (CaiTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed. Results: There were longer APD80, CaiTD80 and increased thresholds of APD and CaiTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor Ca2+ release channel were upregulated, and the subunit of L-type Ca2+ current and sarcoplasmic reticulum Ca2+-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group. Conclusions: IL-17 enhanced CaiTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.

AB - Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Cai) handling and VA susceptibility by IL-17. Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Cai transient duration (CaiTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed. Results: There were longer APD80, CaiTD80 and increased thresholds of APD and CaiTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor Ca2+ release channel were upregulated, and the subunit of L-type Ca2+ current and sarcoplasmic reticulum Ca2+-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group. Conclusions: IL-17 enhanced CaiTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.

KW - alternans

KW - IL-17

KW - IL-17 neutralizer

KW - the maximum calcium transient

KW - ventricular arrhythmias

UR - http://www.scopus.com/inward/record.url?scp=85105950217&partnerID=8YFLogxK

U2 - 10.3389/fcvm.2021.623510

DO - 10.3389/fcvm.2021.623510

M3 - Article

AN - SCOPUS:85105950217

SN - 2297-055X

VL - 8

JO - Frontiers in Cardiovascular Medicine

JF - Frontiers in Cardiovascular Medicine

M1 - 623510

ER -

Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this