PDF(Pubmed)
Abstract：
Arrhythmia and cardiac hypertrophy are two very common cardiovascular diseases that can lead to heart failure and even sudden death, thus presenting a serious threat to human life and health. According to global statistics, nearly one million people per year die from arrhythmia, cardiac hypertrophy and other associated cardiovascular diseases. Hence, there is an urgent need to find new treatment targets and to develop new intervention measures. Recently, mitochondrial dysfunction has been examined in relation to heart disease with a view to lowering the incidence of arrhythmia and cardiac hypertrophy. The heart is the body\'s largest energy consuming organ, turning over about 20 kg of adenosine triphosphate (ATP) per day in the mitochondria. Mitochondrial oxidative phosphorylation (OXPHOS) produces up to 90% of the ATP needed by cardiac muscle cells for contraction and relaxation. Dysfunction of heart mitochondria can therefore induce arrhythmia, cardiac hypertrophy and other cardiovascular diseases. Mitochondrial DNA (mtDNA) mutations cause disorders in OXPHOS and defects in the synthesis of muscle contraction proteins. These lead to insufficient production of secondary ATP, increased metabolic requirements for ATP by the myocardium, and the accumulation of reactive oxygen species (ROS). The resulting damage to myocardial cells eventually induces arrhythmia and cardiac hypertrophy. Mitochondrial damage decreases the efficiency of energy production, which further increases the production of ROS. The accumulation of ROS causes mitochondrial damage and eventually leads to a vicious cycle of mitochondrial damage and low efficiency of mitochondrial energy production. In this review, the mechanism underlying the development of arrhythmia and cardiac hypertrophy is described in relation to mitochondrial energy supply, oxidative stress, mtDNA mutation and Mitochondrial dynamics. Targeted therapy for arrhythmia and cardiac hypertrophy induced by mitochondrial dysfunction is also discussed in terms of its potential clinical value. These strategies should improve our understanding of mitochondrial biology and the pathogenesis of arrhythmia and cardiac hypertrophy. They may also identify novel strategies for targeting mitochondria in the treatment of these diseases.
摘要：
心律失常和心肌肥厚是两种非常常见的心血管疾病，可导致心力衰竭甚至猝死，从而对人类的生命和健康构成严重威胁。根据全球统计数据，每年有近一百万人死于心律失常,心脏肥大和其他相关的心血管疾病。因此，迫切需要寻找新的治疗目标并开发新的干预措施。最近,为了降低心律失常和心肌肥大的发生率，已经研究了线粒体功能障碍与心脏病的关系。心脏是人体最大的耗能器官,每天在线粒体中转移约20公斤三磷酸腺苷（ATP）。线粒体氧化磷酸化（OXPHOS）产生心肌细胞收缩和舒张所需的高达90％的ATP。心脏线粒体功能障碍可诱发心律失常,心脏肥大和其他心血管疾病。线粒体DNA（mtDNA）突变导致OXPHOS疾病和肌肉收缩蛋白合成缺陷。这些导致次级ATP的产生不足，心肌对ATP的代谢需求增加，和活性氧（ROS）的积累。由此产生的对心肌细胞的损伤最终引起心律失常和心脏肥大。线粒体损伤降低了能量生产的效率，这进一步增加了ROS的产量。ROS的积累引起线粒体损伤并最终导致线粒体损伤的恶性循环和线粒体能量产生的低效率。在这次审查中,心律失常和心肌肥厚发展的潜在机制被描述为与线粒体能量供应有关，氧化应激，mtDNA突变和线粒体动力学。针对线粒体功能障碍引起的心律失常和心肌肥厚的靶向治疗也就其潜在的临床价值进行了讨论。这些策略应提高我们对线粒体生物学以及心律失常和心脏肥大的发病机理的理解。他们还可以确定在治疗这些疾病中靶向线粒体的新策略。
