Specific circulating microRNA signature of bicuspid aortic valve disease

• Published in: Journal of translational medicine Vol. 15; no. 1; p. 76
• Main Authors: Martínez-Micaelo, Neus, Beltrán-Debón, Raúl, Baiges, Isabel, Faiges, Marta, Alegret, Josep M
• Format: Journal Article
• Language: English
• Published: England BioMed Central 11.04.2017; BMC
• Subjects: Adult; Age; AKT protein; Aneurysm; Aneurysms; Angiogenesis; Antisense; Antisense RNA; Aorta; Aortic dilation; Aortic valve; Aortic Valve - abnormalities; Aortic Valve - pathology; Bicuspid aortic valve; Bicuspid Aortic Valve Disease; Bioindicators; Biomarkers; Blood; Blood circulation; Body mass; Body weight; Calcification; Calcification (ectopic); Cancer; Cardiovascular disease; Cardiovascular diseases; Cell proliferation; Circulation; Cohort Studies; Coronary artery disease; Coronary vessels; Dilatation, Pathologic; Dissection; Ejection; Evaluation; Female; Flow characteristics; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Growth factors; Heart diseases; Heart Valve Diseases - blood; Heart Valve Diseases - diagnostic imaging; Heart Valve Diseases - genetics; Heart Valve Diseases - pathology; Humans; Hypertension; Liver; Liver transplantation; Logistic Models; Male; Mercury; Metabolism; microRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Morphogenesis; Myocardial infarction; Neurodegenerative diseases; Nucleic acids; Ovarian cancer; Population studies; Proteins; Real-Time Polymerase Chain Reaction; Regulations; Regulators; Reproducibility of Results; Resonance; Revisions; Rheumatic heart disease; Ribonucleic acid; RNA; Rodents; Signal transduction; Smooth muscle; Statins; Statistical methods; Surgery; Transforming growth factor-b1; Transplantation; Ultrasonic imaging; Vascular endothelial growth factor; Ventricle; microRNA; Aortic dilation; Bicuspid aortic valve
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-017-1176-x

We aimed to determine the circulating miRNA expression profile associated with BAV and aortic dilation to provide diagnostic and prognostic biomarkers for BAV and/or aortic dilation. We applied a miRNome-wide microarray approach using plasma samples (n = 24) from healthy tricuspid aortic valve individuals, BAV patients and BAV patients with aortic dilation to compare and identify the specific miRNAs associated with BAV and aortic dilation. In a second stage, the expression patterns of the miRNA candidates were validated by RT-qPCR in an independent cohort (n = 43). The miRNA microarray data and RT-qPCR analyses revealed that the expression levels of circulating miR-122, miR-130a and miR-486 are significantly influenced by the morphology of the aortic valve (bicuspid/tricuspid) and could be functionally involved in the regulation of TGF-β signalling. Furthermore, the expression pattern of miR-718 in the plasma was strongly influenced by dilation of the ascending aorta. miR-718 expression was inversely correlated with the aortic diameter (R = -0.63, p = 3.1 × 10 ) and was an independent predictor of aortic dilation (β = -0.41, p = 0.022). The genes targeted by miR-718 are involved in the regulation of vascular remodelling. We propose that miR-122, miR-130a, miR-486 and miR-718 are new molecular features associated with BAV and aortic dilation principally by the activation of TGF-β pathway and vascular remodelling mediated by VEGF signalling pathways.