Associations Between MicroRNA and Abdominal Aortic Aneurysm Diameter Differ by Sex

<b>Objective:</b> Abdominal aortic aneurysm (AAA) epidemiology differs significantly between the sexes; the biological factors behind this are mostly unknown. MicroRNAs (miRNAs) are short RNA molecules providing post-transcriptional regulation of protein synthesis. Several miRNAs have been associated with the development and growth of AAA, but only in men. We investigated whether the associations between some selected miRNAs and aortic size differ by sex and the possible target pathways for such differences. <b>Methods:</b> A cross-sectional study included subjects with AAA (30-58 mm) and normal aortas. Clinical data were collected through questionnaires. Abdominal aortic diameters were measured using ultrasound. The levels of 17 miRNAs were measured in plasma. The association between miRNA levels, aortic diameter, and sex were analysed using multivariable linear regression. <b>Results:</b> A total of 242 subjects were included, with 85 women and 157 men. In the group with aortic diameters below 30 mm were 122 men (15-29 mm) and 50 women (13-29 mm). There were 35 men (30-54 mm) and 35 women (30-58 mm) with AAA. The associations between six miRNAs and aortic diameter were influenced by sex: miR-125 (<i>p</i> = 0.013), miR-128-1 (<i>p</i> = 0.017), miR-24 (<i>p</i> = 0.013), miR-26a (<i>p</i> = 0.022), miR-93 (<i>p</i> = 0.0015), and miR-194 (<i>p</i> = 0.013). Bioinformatic analysis indicated Hippo and TGF-beta as the two signalling pathways most likely affected by these differences. <b>Conclusions:</b> This exploratory study found sex differences in the associations between miRNA levels and aortic diameter, involving signalling pathways that control organ size and maintain tissue homeostasis by regulating cell proliferation, survival, and differentiation.