Medial tunica degeneration of the ascending aortic wall is associated with specific microRNA changes in bicuspid aortic valve disease

Abstract

Ascending aortic diameter is not an accurate parameter for surgical indication in patients with bicuspid aortic valve (BAV). Thus, the present study aimed to identify specific microRNAs (miRNAs/miRs) and their expression levels in aortic wall aneurysm associated with BAV according to severity of medial degeneration and to elucidate the association between the tissue expression levels of the miRNAs with their expression in plasma. Aortic wall and blood specimens were obtained from 38 patients: 12 controls and 26 patients with BAV with ascending aortic aneurysm. Of the patients with BAV, 19 had cusp fusions of right and left, 5 of right and non-coronary, and 2 of left and non-coronary. Two groups of patients were identified according to the grade of medial degeneration (MD): Low-grade D group (LGMD) and high-grade MD group (HGMD). Expression level of miR-122, miR-130, miR-718 and miR-486 were validated by reverse transcription-quantitative PCR in plasma and tissue samples. MD grade was found to be independent from the BAV phenotype. The HGD group showed increased expression levels of MMP-9 and MMP-2, and an increase in the number of apoptotic cells. Tissue expression levels of miR-718 and miR-122 were lower in the LGMD and HGD groups compared with expression in the control group; the HGD group showed increased levels of miR-486. Plasma expression levels of miR-122 were decreased in the LGMD and HGD groups, and miR-718 was only reduced in the HGD group. On the contrary, expression of miR-486 was increased in the LGMD and HGD groups. The data suggested that miR-486 may be considered as a non-invasive biomarker of aortic wall degeneration. Dysregulation of this putative biomarker may be associated with high risk of dissection and rupture in patients with BAV.