Expression Patterns of Circulating microRNAs in Different Valvulo-aortic Phenotypes

Objectives: Aortic size-based criteria are of limited value in the prediction of aortic events, while most aortic events occur in patients with aortic diameters < 50 mm threshold indication for elective surgery. Therefore, serological biomarkers and especially microRNAs (miRNAs) have been proposed as an elegant tool to improve risk assessment in patients with different aortopathies. We aimed to evaluate the levels of circulating miRNAs in a surgical cohort of patients presenting with distinct valvuloaortic phenotypes.

Methods: We prospectively analyzed a consecutive surgical cohort of 145 patients with distinct valvuloaortic phenotypes referred for aortic valve surgery: (1) 63 patients (mean age 47 ± 11 years, 92% male) with bicuspid aortic valve regurgitation and root dilatation (BAV-AR), (2) 32 patients (mean age 59 ± 11 years, 73% male) with bicuspid aortic valve stenosis (BAV-AS), and (3) 50 patients (mean age 56 ± 14 years, 55% male) with tricuspid aortic valve stenosis and normal aortic root diameters (TAV-AS) who underwent aortic valve ± proximal aortic surgery at a single institution. miRNAs analysis included 11 miRNAs, all published previously in association with aortopathies. Total RNA was extracted in the whole study cohort (PaxGene Blood iRNA kit) and specific miRNAs were identified using TaqMan Advanced miRNA platform. End points of our study were (1) correlation between circulating miRNAs and aortic diameter in mm and (2) comparison of circulating miRNAs in distinct valvuloaortic phenotypes.

Results: There was a significant inverse linear correlation between circulating miRNAs and proximal aortic diameter in the whole study cohort. The strongest correlation was found for miR-17 (r = −0.5, p < 0.001), miR-20a (r = −0.48, p < 0.001), and miR-106a (r = −0.42, p < 0.001). All seven detectable miRNAs were significantly down-regulated in BAV versus TAV with normal aortic root dimensions, in particular, with regard to miR-17(1.1 vs. 3.5; p < 0.001) and miR-145 (0.03 vs. 5.3; p < 0.001).

Conclusion: Our preliminary data demonstrate a significant association between circulating miRNAs and the maximal aortic diameter. When comparing miRNA expression patterns of BAV versus TAV patients with normal aortic root dimensions, BAV patients showed significant down-regulation of circulating miRNA as compared with their TAV counterparts. Further multicenter analyses in larger cohorts and additional valvuloaortic phenotypes are needed to confirm and further validate these results.