Molecular and haemodynamic interplay in bicuspid aortic valve aortopathy: segmental differences across the aortic circumference

Abstract Background Bicuspid aortic valve (BAV) patients develop ascending (AAo) dilation. The pathogenesis of BAV-aortopathy (genetic vs. hemodynamic) remains unclear. Purpose To identify regional changes around the AAo wall in BAV with aortopathy integrating clinical imaging and molecular data. Methods (n=20) were recruited prospectively to surgically collect tissue perform four-dimensional cardiac magnetic resonance (CMR) scans. Molecular markers measured analysing biopsies (n=15) shear stress (WSS) across circumference was calculated from 4D CMR data (n=11 patients, n=7 additional healthy volunteers for comparison). Dilated (anterior/right) non-dilated (posterior/left) circumferential segments profiled whole genomic microRNAs (Next Generation RNA-Sequencing, miRCURY LNA PCR), proteins content (Tandem Mass Spectrometry) elastin fragmentation degeneration (histomorphometric analysis). Picture 1 summarises study approach (including a map divided following segments: A=anterior, AR=anterior-right, PR=posterior-right, P=posterior, PL=posterior-left, AL=anterior-left). Results Integrated bioinformatic analyses RNA-sequencing proteomic datasets identified 5 (miR-128-3p, miR-210-3p, miR-150-5p, miR-199b-5p, miR-21-5p) differentially expressed circumference. Among them, three miRNAs miR-199b-5p) predicted have an effect on eight common target genes, whose expression dysregulated according involved vascular endothelial growth factor signalling, hippo signaling arachidonic acid pathway. Decreased elastic fibre levels layer thickness observed dilated histomorphometric analysis. Increased WSS flow-velocity, helical streamlines asymmetrical flow at anterior/right asymmetrically symmetrically (the latter exhibiting higher WSS), compared volunteers. Conclusion This has newly revealed concomitant expressional dysregulation miRNAs, proteins, fibres corresponding regions elevated WSS, contributing advance understanding interplay genetic hemodynamic factors underpinning aortopathy. Funding Acknowledgement Type funding sources: Foundation. Main source(s): British Heart Foundation Above & Beyond