The Role of Blood-derived Exosomal hsa-miR-130a-5p from Abdominal Aortic Aneurysm patients in Human Aortic Smooth Muscle Cells

Abstract

Abdominal aortic aneurysm (AAA) is a perilous condition involving pathological dilation of the aortic wall. AAA is also a disease known to be associated with the proliferation and apoptosis of aorta smooth muscle cells (AoSMC). Therefore, due to the asymptomatic course and rupture of this disease with dangerous consequences, the biomarker identification for early diagnosis is of great important for clinical benefit. Abnormal phenotypic switch, migration, and proliferation of AoSMCs are hallmarks for pathogenesis of AAA. This study, we identified miR-130a-5p as a critical regulator controlling human AoSMC phenotypic switch and migration to investigate whether miR-130a-5p affects human AoSMC functions and development of AAA. Using miRNA sequencing of blood-derived exosomes from 7 AAA and 2 controls, we identified significantly downregulated hsa-miR-130a-5p within blood-derived exosomes from AAA blood. Ectopic expression of hsa-miR-130a-5p evidently promoted AoSMC differentiation and expression of contractile markers, such as a-SMA, SM22a, MYH11 and CNN1. hsa-miR-130a-5p potently inhibited PDGF-BB induced AoSMC phenotypic switch and migration. We further identified myocardin(MYOCD), SP-1 and TCF21 as downstream targets of hsa-miR- 134-5p in human AoSMCs and proved them to be mediators in AoSMC phenotypic switch and progression of AAA. The study results revealed that hsa-miR-130a-5p was a novel regulator in vascular remodeling and pathological progress of AAA via targeting TCF21/MYOCD expression. In conclusion, targeting hsa-miR-130a-5p or its downstream molecules in AoSMCs might develop new avenues in clinical treatment of AAA.