Roles and Mechanisms of miRNAs in Abdominal Aortic Aneurysm: Signaling Pathways and Clinical Insights.

Abstract

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.