MicroRNA Profiling of Plasma Extracellular Vesicles in Bicuspid Aortopathy

Abstract Background: Bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease and highly associated with ascending aortic dilation, i.e., bicuspid aortopathy. When the maximal aortic diameter achieves a critical threshold, prophylactic surgical intervention is recommended to prevent potential aortic dissection or rupture. However, the aortic diameter threshold cannot precisely predict the aortopathy progression and should be supplemented by more non-size parameters to provide more information for surgical decision. There is an urgent need for identification of a stable prognostic biomarker for BAV patients with increased risk of aortopathy progression. Methods and Results: In total, 24 patients with BAV and 6 healthy volunteers with tricuspid aortic valve (TAV) were involved in this study. Quantitative proteomics were employed to identify protein expressions in plasma. Sorted by the ratio of transforming growth factor-β1 (TGF-β1) to soluble endoglin (sENG) (T/E), which has been recognized as a plasma protein biomarker for aortopathy progression, BAV patients were divided into two groups with high (≥ 0.5, n = 6) or low (T/E < 0.5, n = 18) ratio of T/E. The mcroiRNA (miR) profiling of plasma extracellular vesicles (EVs) was performed using small RNA sequencing. The results revealed that low ratio of EV-miR324 to miR145 (≤ 0.1) was closely correlated to high ratio of T/E.Conclusions: The ratio of plasma miR324 to miR145 from EVs may identify the risk of progression of BAV aortopathy.