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Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility
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 heart...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007768/ https://www.ncbi.nlm.nih.gov/pubmed/33796569 http://dx.doi.org/10.3389/fcvm.2021.623510 |
Sumario: | 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(i)TD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed. Results: There were longer APD(80), Ca(i)TD(80) and increased thresholds of APD and Ca(i)TD 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(+)/Ca(2+) exchanger, phospholamban, and ryanodine receptor Ca(2+) release channel were upregulated, and the subunit of L-type Ca(2+) current and sarcoplasmic reticulum Ca(2+)-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group. Conclusions: IL-17 enhanced Ca(i)TD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility. |
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