Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing, 100037, China.
Curr Atheroscler Rep. 2024 Jul;26(7):273-287. doi: 10.1007/s11883-024-01204-8. Epub 2024 May 6.
Abdominal aortic aneurysm refers to a serious medical condition that can cause the irreversible expansion of the abdominal aorta, which can lead to ruptures that are associated with up to 80% mortality. Currently, surgical and interventional procedures are the only treatment options available for treating abdominal aortic aneurysm patients. In this review, we focus on the upstream and downstream molecules of the microRNA-related signaling pathways and discuss the roles, mechanisms, and targets of microRNAs in abdominal aortic aneurysm modulation to provide novel insights for precise and targeted drug therapy for the vast number of abdominal aortic aneurysm patients.
Recent studies have highlighted that microRNAs, which are emerging as novel regulators of gene expression, are involved in the biological activities of regulating abdominal aortic aneurysms. Accumulating studies suggested that microRNAs modulate abdominal aortic aneurysm development through various signaling pathways that are yet to be comprehensively summarized. A total of six signaling pathways (NF-κB signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, TGF-β signaling pathway, Wnt signaling pathway, and P53/P21 signaling pathway), and a total of 19 miRNAs are intimately associated with the biological properties of abdominal aortic aneurysm through targeting various essential molecules. MicroRNAs modulate the formation, progression, and rupture of abdominal aortic aneurysm by regulating smooth muscle cell proliferation and phenotype change, vascular inflammation and endothelium function, and extracellular matrix remodeling. Because of the broad crosstalk among signaling pathways, a comprehensive analysis of miRNA-mediated signaling pathways is necessary to construct a well-rounded upstream and downstream regulatory network for future basic and clinical research of AAA therapy.
腹主动脉瘤是一种严重的医学病症,可导致腹主动脉的不可逆扩张,进而导致破裂,破裂可导致高达 80%的死亡率。目前,手术和介入治疗是治疗腹主动脉瘤患者的唯一选择。在本综述中,我们重点关注与 microRNA 相关信号通路的上下游分子,并讨论 microRNA 在腹主动脉瘤调节中的作用、机制和靶点,为广大腹主动脉瘤患者的精准靶向药物治疗提供新的见解。
最近的研究表明,microRNA 作为基因表达的新兴调节因子,参与调节腹主动脉瘤的生物学活性。越来越多的研究表明,microRNA 通过各种信号通路调节腹主动脉瘤的发生和发展,而这些信号通路尚未得到全面总结。NF-κB 信号通路、PI3K/AKT 信号通路、MAPK 信号通路、TGF-β 信号通路、Wnt 信号通路和 P53/P21 信号通路等 6 个信号通路,以及总共 19 个 microRNA,通过靶向各种关键分子,与腹主动脉瘤的生物学特性密切相关。microRNA 通过调节平滑肌细胞的增殖和表型变化、血管炎症和内皮功能以及细胞外基质重塑,调节腹主动脉瘤的形成、进展和破裂。由于信号通路之间广泛的相互作用,需要对 microRNA 介导的信号通路进行全面分析,以构建一个全面的上游和下游调控网络,为未来腹主动脉瘤治疗的基础和临床研究提供参考。