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Published on: December 22, 2023
Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility
Yung-Nan Tsai1,2, Ya-Wen Hsiao2, Shien-Fong Lin3
1Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Insights
Interleukin-17 (IL-17) disrupts intracellular calcium handling, prolonging action potential duration and increasing susceptibility to ventricular arrhythmias (VA). This mechanism highlights IL-17
Area of Science:
- Cardiovascular Physiology
- Electrophysiology
- Molecular Cardiology
Background:
- The precise mechanisms by which Interleukin-17 (IL-17) contributes to ventricular arrhythmias (VA) are not fully understood.
- Investigating the role of intracellular calcium (Cai) handling in IL-17-induced VA is crucial for understanding cardiac arrhythmogenesis.
Purpose of the Study:
- To elucidate the impact of IL-17 on intracellular calcium handling and its subsequent effect on ventricular arrhythmia susceptibility.
- To examine the electrophysiological consequences of IL-17 exposure in isolated rabbit hearts.
Main Methods:
- Utilized optical mapping to assess electrophysiological properties in isolated perfused rabbit hearts exposed to IL-17.
- Measured action potential duration (APD) and Cai transient duration (CaiTD), and analyzed ion channel mRNA expression via RT-PCR.
- Compared hearts treated with IL-17, IL-17 with neutralizer, and baseline controls.
Main Results:
- IL-17 exposure led to prolonged APD80 and CaiTD80, with increased thresholds for alternans and VA induction.
- Ventricular fibrillation analysis revealed a higher number of phase singularities and dominant frequency in the IL-17 group.
- Observed upregulation of Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor mRNA, alongside downregulation of L-type Ca2+ current and SERCA2a.
Conclusions:
- IL-17 exacerbates CaiTD and APD alternans by disrupting cardiac calcium handling mechanisms.
- These calcium handling disturbances induced by IL-17 significantly increase susceptibility to ventricular arrhythmias.
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.
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