Zhang Yiyu, Huang Guoqing, Yuan Zhaohu, Zhang Yonggang, Chang Rong
Department of Blood Transfusion, Department of Cardiology, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, China.
Department of Blood Transfusion, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Front Cell Dev Biol. 2021 Dec 17;9:760515. doi: 10.3389/fcell.2021.760515. eCollection 2021.
Dilated cardiomyopathy (DCM) is a type of heart disease delimited by enlargement and dilation of one or both of the ventricles along with damaged contractility, which is often accompanied by the left ventricular ejection fraction (LVEF) less than 40%. DCM is progressive and always leads to heart failure. Circular RNAs (circRNAs) are unique species of noncoding RNAs featuring high cell-type specificity and long-lasting conservation, which normally are involved in the regulation of heart failure and DCM recently. So far, a landscape of various single gene or polygene mutations, which can cause complex human cardiac disorders, has been investigated by human-induced pluripotent stem cell (hiPSC) technology. Furthermore, DCM has been modeled as well, providing new perspectives on the disease study at a cellular level. In addition, current genome editing methods can not only repair defects of some genes, but also rescue the disease phenotype in patient-derived iPSCs, even introduce pathological-related mutations into wild-type strains. In this review, we gather up the aspects of the circRNA expression and mechanism in the DCM disease scenario, facilitating understanding in DCM development and pathophysiology in the molecular level. Also, we offer an update on the most relevant scientific progress in iPSC modeling of gene mutation-induced DCM.
扩张型心肌病（DCM）是一种心脏病，其特征为一个或两个心室扩大和扩张，同时伴有收缩功能受损，常伴有左心室射血分数（LVEF）低于40%。DCM是进行性的，常导致心力衰竭。环状RNA（circRNAs）是一类独特的非编码RNA，具有高度的细胞类型特异性和长期保守性，最近通常参与心力衰竭和DCM的调控。到目前为止，人类诱导多能干细胞（hiPSC）技术已经研究了各种单基因或多基因突变的情况，这些突变可导致复杂的人类心脏疾病。此外，DCM也已被建模，为细胞水平的疾病研究提供了新的视角。此外，目前的基因组编辑方法不仅可以修复某些基因的缺陷，还可以挽救患者来源的诱导多能干细胞中的疾病表型，甚至将与病理相关的突变引入野生型菌株。在这篇综述中，我们总结了DCM疾病情况下circRNA的表达和机制，有助于在分子水平上理解DCM的发展和病理生理学。此外，我们还提供了关于基因突变诱导的DCM的iPSC建模方面最相关科学进展的最新情况。
