Tissue and circulating miRNAs as biomarkers in bicuspid aortic valve disease.

Recent data suggested that bicuspid aortic valve (BAV) with left-right (L-R), right-non coronary (R-NC) and left-non coronary (L-NC) cusp fusion represents distinct pathological entities1. The rate of aortic enlargement varies according to the pattern of cusps fusion, with faster rates of aortic sinus and ascending aortic dilatation associated with the L-R compared to R-NC and L-NC morphology. In our study, we sought to investigate the histological fea-tures of aneurysms associated to different BAV phenotypes and we looked for specific mi-croRNAs (miRNA) as biomarkers of medial degeneration severity in order to optimize surgi-cal indication and prevent catastrophic complications such as rupture and dissection. Aortic specimens were obtained from BAV patients treated surgically for the repair of tho-racic aortic aneurysm (TAA). Histopathological and immunohistochemical analyses were performed to assess the ascending aorta wall degeneration. Plasma was obtained from blood and in a second stage, the expression patterns of the miRNA candidates (miR-122, miR-130, miR-718, miR-486) were validated by RT-qPCR. The morphological analyses showed severe medial degeneration in the aorta of BAV pa-tients with R-L phenotype, moderate medial degeneration in patients with R-NC phenotype and faint medial degeneration in patients with L-NC. The data obtained by RT-qPCR re-vealed that the expression of miR-122, miR-130, miR-718 and miR-486 are influenced by the morphology of the BAV and the severity of aortic wall degeneration. In particular, the down-regulation of miR-122, miR-130, miR-718 and the up-regulation of miR-486 were more sig-nificant in BAV patients with R-L phenotype and severe medial degeneration. Morphologic and genetic features of TAA vary according to the pattern of BAV cusp fu-sion with severe medial cystic degeneration of the aortic wall associated with the L-R com-pared to R-NC and L-NC morphologies. Here, we proposed that miR-122, miR-130, miR-718, miR-486 can be considered new markers associated with severe medial degeneration in BAV patients with aortic dilatation. A significant dysregulation of these biomarkers might be associated with high risk of dissection and rupture.