Role of miR-21-5p in the pathogenesis of abdominal aortic aneurysm regarding the Th17 pathway.

Background and aims: The interplay between Th17-related immune activity and miRNA-driven regulation in abdominal aortic aneurysm (AAA) pathogenesis remains poorly understood. In this prospective study, we aimed to assess the potential role of miR-21-5p corresponding to the Th17 pathway disturbances in the development of AAA. Methods: Biological samples were collected from patients with true infrarenal AAA, undergoing elective open abdominal aortic surgery, and patients with peripheral arterial disease (PAD) without concomitant aneurysms on the day of hospital admission for surgery. A fragment of aneurysmal abdominal aortic tissue was collected from patients intraoperatively. Total RNA was extracted from the samples, and the expression level of miR-21-5p and selected markers associated with Th17 pathway were assessed using quantitative real-time PCR (RT-qPCR) and Luminex assays, respectively. Moreover, we performed an in vitro model using human endothelial cells, transfected with a synthetic miR-21-5p mimic. Results: We included 60 patients (30 in the study group and 30 in the control group, selected based on the propensity score matching method). Circulating miR-21-5p levels were significantly higher in AAA patients compared to controls. miR-21-5p downregulates genes involved in endothelial development, regulation of vascular permeability, or endothelial cell response to growth factors. We demonstrated that the Th17 circulating mediators were higher among AAA patients compared to controls, and were higher in the middle part of the aneurysmal aorta when compared to its upper pole. Conclusion: Our study showed that, regarding AAA pathogenesis, endothelial dysfunction followed by inflammation could be mediated by an increased level of miR-21-5p.