Yang Xi, Yang Yanyan, Guo Junjie, Meng Yuanyuan, Li Min, Yang Panyu, Liu Xin, Aung Lynn Htet Htet, Yu Tao, Li Yonghong
Department of Cardiology, The Affiliated Hospital of Qingdao University, Road No. 59 Haier, Qingdao 266100, Shandong, People's Republic of China.
Department of Immunology, School of Basic Medicine, Qingdao University, No. 308 Ningxia Road, Qingdao 266071, People's Republic of China.
Mol Ther Nucleic Acids. 2021 Jan 26;23:1136-1160. doi: 10.1016/j.omtn.2021.01.024. eCollection 2021 Mar 5.
Coronary artery disease (CAD) is one of the most common causes of death worldwide. The introduction of percutaneous revascularization has revolutionized the therapy of patients with CAD. Despite the advent of drug-eluting stents, restenosis remains the main challenge in treating patients with CAD. In-stent restenosis (ISR) indicates the reduction in lumen diameter after percutaneous coronary intervention, in which the vessel's lumen re-narrowing is attributed to the aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) and dysregulation of endothelial cells (ECs). Increasing evidence has demonstrated that epigenetics is involved in the occurrence and progression of ISR. In this review, we provide the latest and comprehensive analysis of three separate but related epigenetic mechanisms regulating ISR, namely, DNA methylation, histone modification, and non-coding RNAs. Initially, we discuss the mechanism of restenosis. Furthermore, we discuss the biological mechanism underlying the diverse epigenetic modifications modulating gene expression and functions of VSMCs, as well as ECs in ISR. Finally, we discuss potential therapeutic targets of the small molecule inhibitors of cardiovascular epigenetic factors. A more detailed understanding of epigenetic regulation is essential for elucidating this complex biological process, which will assist in developing and improving ISR therapy.
冠状动脉疾病（CAD）是全球最常见的死亡原因之一。经皮血管重建术的引入彻底改变了CAD患者的治疗方式。尽管药物洗脱支架问世，但再狭窄仍然是治疗CAD患者的主要挑战。支架内再狭窄（ISR）是指经皮冠状动脉介入治疗后管腔直径减小，其中血管腔再次狭窄归因于血管平滑肌细胞（VSMC）异常增殖和迁移以及内皮细胞（EC）功能失调。越来越多的证据表明，表观遗传学参与了ISR的发生和发展。在本综述中，我们对调节ISR的三种独立但相关的表观遗传机制，即DNA甲基化、组蛋白修饰和非编码RNA，进行了最新的全面分析。首先，我们讨论再狭窄的机制。此外，我们讨论了调节VSMC以及ISR中EC的基因表达和功能的各种表观遗传修饰的生物学机制。最后，我们讨论心血管表观遗传因子小分子抑制剂的潜在治疗靶点。更详细地了解表观遗传调控对于阐明这一复杂的生物学过程至关重要，这将有助于开发和改进ISR治疗方法。
