Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
Dezhou Second People's Hospital, Dezhou 253000, China.
Pharmacol Res. 2022 Jan;175:106027. doi: 10.1016/j.phrs.2021.106027. Epub 2021 Dec 7.
Cardiac arrhythmia occurs frequently worldwide, and in severe cases can be fatal. Mitochondria are the power plants of cardiomyocytes. In recent studies, mitochondria under certain stimuli produced excessive reactive oxygen species (ROS), which affect the normal function of cardiomyocytes through ion channels and related proteins. Mitochondrial oxidative stress (MOS) plays a key role in diseases with multifactorial etiopathogenesis, such as arrhythmia; MOS can lead to arrhythmias such as atrial fibrillation and ventricular tachycardia. This review discusses the mechanisms of arrhythmias caused by MOS, particularly of ROS produced by mitochondria. MOS can cause arrhythmias by affecting the activities of Ca-related proteins, the mitochondrial permeability transition pore protein, connexin 43, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, and ion channels. Based on these mechanisms, we discuss possible new treatments for arrhythmia. Targeted treatments focusing on mitochondria may reduce the progression of arrhythmias, as well as the occurrence of severe arrhythmias, and may be effective for personalized disease prevention.
心律失常在全球范围内频繁发生，在严重的情况下可能致命。线粒体是心肌细胞的“动力工厂”。在最近的研究中，线粒体在某些刺激下会产生过多的活性氧（ROS），通过离子通道和相关蛋白影响心肌细胞的正常功能。线粒体氧化应激（MOS）在多因素发病机制的疾病中起着关键作用，如心律失常；MOS 可导致心房颤动和室性心动过速等心律失常。本文讨论了由 MOS 引起心律失常的机制，特别是由线粒体产生的 ROS 引起的心律失常。MOS 可以通过影响 Ca 相关蛋白、线粒体通透性转换孔蛋白、连接蛋白 43、超极化激活环核苷酸门控钾通道 4 和离子通道的活性来引起心律失常。基于这些机制，我们讨论了心律失常的可能新治疗方法。针对线粒体的靶向治疗可能会减缓心律失常的进展以及严重心律失常的发生，并且可能对个性化疾病预防有效。
