Qiao Lin, Fan Xuehui, Yang Zhen, El-Battrawy Ibrahim, Zhou Xiaobo, Akin Ibrahim
Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China.
J Cardiovasc Dev Dis. 2022 Mar 4;9(3):76. doi: 10.3390/jcdd9030076.
Recent studies indicate that the disorder of glucose metabolism in myocardial tissue is involved in the development of Takotsubo syndrome (TTS). This study investigated the effects of a high level of glucose on the pathogenesis of TTS, focusing on the electrophysiological mechanisms. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with toxic concentration of isoprenaline (Iso, 1 mM) and a high level of glucose (22 mM) to mimic the setting of TTS and diabetes mellitus (DM). Iso prolonged action potential duration (APD) through enhancing the late sodium channel current and suppressing the transient outward potassium current (I). However, a high level of glucose prevented the APD prolongation and the change in I. High-level glucose reduced the expression levels of PI3K/Akt, β1-adrenoceptors, Gs-protein, and PKA, suggesting their involvement in the protective effects of high-level glucose against toxic effects of catecholamine. High glucose level did not influence Iso-induced ROS-generation, suggesting that the protective effects of high-level glucose against Iso did not result from changes in ROS generation. High-level glucose may protect cardiomyocytes from the toxic effects of catecholamine excess through suppressing β1-adrenoceptor-Gs-PKA signaling. DM may reduce the risk for occurrence of arrhythmias due to QT prolongation in TTS patients.
近期研究表明，心肌组织中葡萄糖代谢紊乱与应激性心肌病（TTS）的发生发展有关。本研究聚焦于电生理机制，探讨了高血糖对TTS发病机制的影响。使用毒性浓度的异丙肾上腺素（Iso，1 mM）和高血糖（22 mM）处理人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs），以模拟TTS和糖尿病（DM）的情况。Iso通过增强晚期钠通道电流和抑制瞬时外向钾电流（I）来延长动作电位时程（APD）。然而，高血糖可防止APD延长和I的变化。高血糖降低了PI3K/Akt、β1-肾上腺素能受体、Gs蛋白和PKA的表达水平，表明它们参与了高血糖对儿茶酚胺毒性作用的保护作用。高血糖水平不影响Iso诱导的活性氧生成，表明高血糖对Iso的保护作用并非源于活性氧生成的变化。高血糖可能通过抑制β1-肾上腺素能受体-Gs-PKA信号通路来保护心肌细胞免受儿茶酚胺过量的毒性作用。糖尿病可能降低TTS患者因QT延长而发生心律失常的风险。
