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 journalJournal Article peer-review

3 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 (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.

Original languageEnglish
Article number623510
JournalFrontiers in Cardiovascular Medicine
Volume8
DOIs
StatePublished - 16 03 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Tsai, Hsiao, Lin, Chan, Hsieh, Tang, Lee, Huang, Li, Chao, Higa, Wu, Chang and Chen.

Keywords

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

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