Zhao Yanfang, Ponnusamy Murugavel, Dong Yanhan, Zhang Lei, Wang Kun, Li Peifeng
Centre for Developmental Cardiology, Institute for Translational Medicine, Qingdao University, Qingdao, China.
Clin Exp Pharmacol Physiol. 2017 Apr;44(4):431-440. doi: 10.1111/1440-1681.12720.
Myocardial apoptosis play a vital role in pathogenesis of cardiovascular diseases. The intrinsic pathway of apoptosis (mitochondrial apoptosis pathway) and abnormal mitochondrial fission and fusion have a detrimental effect on cells under a variety of intracellular stresses including hypoxia, oxidative stress, drug toxicity or DNA damage and contributes to the development of heart failure (HF), myocardial infarction (MI), diabetic cardiomyopathy and ischaemia/reperfusion injury (I/R). MicroRNAs (miRNAs) are endogenous short non-coding RNAs, which target 3'-untranslated region of mRNA to switch off gene expression. They play crucial roles in regulating complicated cardiac signalling and transcriptional events during cardiac development as well as in diseased condition. In this review, we summarize the molecular mechanism of mitochondrial apoptosis in cardiac cells and influence of miRNAs on them. MiRNAs regulate cardiac mitochondrial apoptosis by exert their effects on mitochondrial fission and fusion, reactive oxygen species (ROS) generation and Ca homeostasis, Bcl-2 family members, and other mitochondrial function proteins. This advancement in understanding mechanism of cardiac cells death provides us new therapy targets for cardiovascular diseases associated with mitochondrial dysfunctions.
心肌细胞凋亡在心血管疾病的发病机制中起着至关重要的作用。凋亡的内在途径（线粒体凋亡途径）以及异常的线粒体分裂和融合，在包括缺氧、氧化应激、药物毒性或DNA损伤在内的多种细胞内应激状态下，会对细胞产生有害影响，并促进心力衰竭（HF）、心肌梗死（MI）、糖尿病性心肌病和缺血/再灌注损伤（I/R）的发展。微小RNA（miRNA）是内源性短链非编码RNA，其通过靶向mRNA的3'非翻译区来关闭基因表达。它们在心脏发育过程以及疾病状态下调节复杂的心脏信号传导和转录事件中发挥着关键作用。在本综述中，我们总结了心肌细胞中线粒体凋亡的分子机制以及miRNA对其的影响。miRNA通过对线粒体分裂和融合、活性氧（ROS）生成、钙稳态、Bcl-2家族成员以及其他线粒体功能蛋白发挥作用，从而调节心脏线粒体凋亡。对心肌细胞死亡机制的这一进展为我们提供了与线粒体功能障碍相关的心血管疾病的新治疗靶点。
