Nie Xiang, Fan Jiahui, Wang Dao Wen
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, China.
Biology (Basel). 2023 Jan 19;12(2):154. doi: 10.3390/biology12020154.
Cardiac fibrosis remains an unresolved problem in cardiovascular diseases. Fibrosis of the myocardium plays a key role in the clinical outcomes of patients with heart injuries. Moderate fibrosis is favorable for cardiac structure maintaining and contractile force transmission, whereas adverse fibrosis generally progresses to ventricular remodeling and cardiac systolic or diastolic dysfunction. The molecular mechanisms involved in these processes are multifactorial and complex. Several molecular mechanisms, such as TGF-β signaling pathway, extracellular matrix (ECM) synthesis and degradation, and non-coding RNAs, positively or negatively regulate myocardial fibrosis. Long noncoding RNAs (lncRNAs) have emerged as significant mediators in gene regulation in cardiovascular diseases. Recent studies have demonstrated that lncRNAs are crucial in genetic programming and gene expression during myocardial fibrosis. We summarize the function of lncRNAs in cardiac fibrosis and their contributions to miRNA expression, TGF-β signaling, and ECMs synthesis, with a particular attention on the exosome-derived lncRNAs in the regulation of adverse fibrosis as well as the mode of action of lncRNAs secreted into exosomes. We also discuss how the current knowledge on lncRNAs can be applied to develop novel therapeutic strategies to prevent or reverse cardiac fibrosis.
心脏纤维化仍然是心血管疾病中一个尚未解决的问题。心肌纤维化在心脏损伤患者的临床结局中起着关键作用。适度纤维化有利于维持心脏结构和传递收缩力，而不良纤维化通常会进展为心室重构和心脏收缩或舒张功能障碍。这些过程涉及的分子机制是多因素且复杂的。几种分子机制，如转化生长因子-β（TGF-β）信号通路、细胞外基质（ECM）合成与降解以及非编码RNA，对心肌纤维化具有正向或负向调节作用。长链非编码RNA（lncRNAs）已成为心血管疾病基因调控中的重要介质。最近的研究表明，lncRNAs在心肌纤维化过程中的基因编程和基因表达中至关重要。我们总结了lncRNAs在心脏纤维化中的功能及其对miRNA表达、TGF-β信号传导和ECM合成的作用，特别关注外泌体来源的lncRNAs在不良纤维化调节中的作用以及分泌到外泌体中的lncRNAs的作用模式。我们还讨论了如何将目前关于lncRNAs的知识应用于开发预防或逆转心脏纤维化的新型治疗策略。
