Altered MicroRNA Signatures in Circulating Extracellular Vesicles Reflect Aortic Dilation in Takayasu Arteritis

Abstract

Takayasu arteritis (TAK) is a large-vessel vasculitis that can lead to aneurysmal dilation, yet reliable circulating biomarkers for vascular remodelling remain lacking. Extracellular vesicles (EVs) carry miRNAs implicated in vascular biology, but their relevance to TAK has not been fully explored.

Circulating EVs were isolated from serum of 54 patients with TAK and healthy controls (HC), characterized, and profiled for miRNA content. Effects on endothelial cells (ECs) and monocytes were examined in vitro, and the diagnostic performance of EV-associated miR-223-3p for aortic dilation was assessed by ROC analysis.

Circulating EVs from patients with TAK exhibited a distinct miRNA profile compared with HC. HC-EVs reduced the transcript abundance of ICAM-1 and VCAM-1 in ECs, an effect attenuated in TAK-EVs and accompanied by enhanced monocyte adhesion. EV-derived miR-223-3p was upregulated in TAK but selectively downregulated in patients with aortic dilation. EV-associated miR-223-3p discriminated aortic dilation with an AUC of 0.748, exceeding that of CRP and ESR. Flow cytometric profiling revealed a reduction in platelet-derived EVs in patients with aortic dilation.

Reduced EV-associated miR-223-3p is associated with aortic dilation in TAK and may serve as a candidate biomarker as an adjunct to imaging-based assessment, warranting prospective validation in larger cohorts.