Tsai Yung-Nan, Hsiao Ya-Wen, Lin Shien-Fong, Chan Yi-Hsin, Hsieh Yu-Cheng, Tang Wei-Hua, Lee An-Sheng, Huang Yu-Ting, Li Hsing-Yuan, Chao Tze-Fan, Higa Satoshi, Wu Tsu-Juey, Chang Shih-Lin, Chen Shih-Ann
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Division of Cardiology, Department of Medicine, Heart Rhythm Center, Taipei Veterans General Hospital, Taipei, Taiwan.
Front Cardiovasc Med. 2021 Mar 16;8:623510. doi: 10.3389/fcvm.2021.623510. eCollection 2021.
The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Ca) handling and VA susceptibility by IL-17. The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, = 6) and the IL-17 with neutralizer (0.4 μg/ml, = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Ca transient duration (CaTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed. There were longer APD, CaTD and increased thresholds of APD and CaTD 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 exchanger, phospholamban, and ryanodine receptor Ca release channel were upregulated, and the subunit of L-type Ca current and sarcoplasmic reticulum Ca-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group. IL-17 enhanced CaTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.
白细胞介素 -17（IL -17）诱发室性心律失常（VA）的机制尚不清楚。本研究旨在探讨IL -17对细胞内钙（Ca）处理及VA易感性的影响。使用光学标测系统评估了IL -17（20 ng/ml，n = 6）及IL -17与中和剂（0.4 μg/ml，n = 6）作用下离体灌注兔心脏的电生理特性。检测了动作电位时程（APD）和钙瞬变时程（CaTD），并对离子通道进行了半定量逆转录聚合酶链反应分析。与IL -17中和剂组和基线组相比，IL -17组的APD、CaTD更长，APD和CaTD交替变化的阈值增加，APD恢复的最大斜率和VA诱发阈值升高。在心室颤动期间，IL -17组的相位奇点数量和主导频率均显著高于基线组。与基线组和IL -17中和剂组相比，IL -17组钠/钙交换体、受磷蛋白和兰尼碱受体钙释放通道的mRNA表达上调，L型钙电流亚基和肌浆网钙ATP酶2a显著降低。IL -17通过干扰钙处理增强了CaTD和APD交替变化，这可能会增加VA易感性。
