Expression Patterns of Circulating MicroRNAs in the Risk Stratification of Bicuspid Aortopathy

Abstract

Objective: Aortic size-based criteria are of limited value in the prediction of aortic events, while most aortic events occur in patients with proximal aortic diameters < 50 mm. Serological biomarkers and especially circulating microRNAs (miRNAs) have been proposed as an elegant tool to improve risk stratification in patients with different aortopathies. Therefore, we aimed to evaluate the levels of circulating miRNAs in a surgical cohort of patients presenting with bicuspid aortic valve disease and distinct valvulo-aortic phenotypes. Methods: We prospectively examined a consecutive cohort of 145 patients referred for aortic valve surgery: (1) Sixty three patients (mean age 47 ± 11 years, 92% male) with bicuspid aortic valve regurgitation and root dilatation (BAV-AR), (2) thirty two patients (mean age 59 ± 11 years, 73% male) with bicuspid aortic valve stenosis (BAV-AS), and (3) fifty 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. MicroRNAs analysis included 11 miRNAs, all published previously in association with aortopathies. Endpoints of our study were (1) correlation between circulating miRNAs and aortic diameter and (2) comparison of circulating miRNAs in distinct valvulo-aortic phenotypes. Results: We found a significant inverse linear correlation between circulating miRNAs levels and proximal aortic diameter in the whole study cohort. The strongest correlation was found for miR-17 (r = −0.42, p < 0.001), miR-20a (r = −0.37, p < 0.001), and miR-106a (r = −0.32, p < 0.001). All miRNAs were significantly downregulated in BAV vs. TAV with normal aortic root dimensions Conclusions: Our data demonstrate a significant inverse correlation between circulating miRNAs levels and the maximal aortic diameter in BAV aortopathy. When comparing miRNAs expression patterns in BAV vs. TAV patients with normal aortic root dimensions, BAV patients showed significant downregulation of analyzed miRNAs as compared to their TAV counterparts. Further multicenter studies in larger cohorts are needed to further validate these results.

The top-100 most cited articles of biomarkers in congenital heart disease: a bibliometric analysis

“…There is a growing interest to use circulating biomarkers for risk stratification in patients with CHD such as bicuspid aortic valve. The following biomarkers are being focused on: matrix metalloproteinases (MMPs), transforming growth factor β (TGF-β), tissue inhibitors of matrix metalloproteinases (TIMPs), alpha1antitrypsin, as well as non-coding microRNAs (47,48). Cluster III represented biomarkers in secondary injury after cardiopulmonary bypass in children with CHD, such as Neutrophil gelatinase-associated lipocalin (NGAL) and SB100 protein, which mainly involved the prediction and evaluation of kidney injury and brain injury after extracorporeal circulation (49,50).…”

Circulating microRNAs in the prediction of BAV aortopathy: do the expression patterns correlate between blood and aortic tissue?

“…In former series, we showed the correlation between aortic miRs and matrix metalloproteinases (MMP)/tissue inhibitors of matrix metalloproteinases (TIMP) [12] and between peripheral whole blood miRs and aortic diameter [10]. Wu et al [13] performed a paired comparison of the miR expression between severely dilated vs. normal appearing, less-dilated aortic samples.…”

“…Peripheral whole blood for miRs analysis was sampled just before the surgery (i.e., during anesthesia induction). The expression of 10 miRs was analyzed in the intraoperatively obtained aortic tissue and peripheral whole blood (miR-1, miR-17, miR-18a, miR-19a, miR-20a, miR-21, miR-106a, miR-133a, miR-143 and miR-145), all published previously in association with aortopathies [3,10]. Primary study endpoint was the correlation between the miRs in the aortic tissue and the peripheral whole blood.…”

MicroRNAs involve in bicuspid aortic aneurysm: pathogenesis and biomarkers

“…By A. Gallo et al, miR-15b was found to be an independent predictor of aortic dilatation, and the circulating level of miR-34a was negatively correlated with aortic wall elasticity in patients with BAV [ 59 ]. Lately a significant negative linear correlation was found between circulating miR-17, miR-20a, miR-106a and proximal aortic diameter [ 60 ].…”