title: Specific circulating microRNA signature of bicuspid aortic valve disease.
abstract: 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-β1signalling. 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 × 10-5) 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-β1pathway and vascular remodelling mediated by VEGF signalling pathways.
authors.affiliation: Grup de Recerca Cardiovascular, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Martínez-Micaelo
authors.affiliation: Grup de Recerca Cardiovascular, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Beltrán-Debón
authors.affiliation: Centre for Omic Sciences (COS), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Baiges
authors.affiliation: Grup de Recerca Cardiovascular, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Faiges
authors.affiliation: Grup de Recerca Cardiovascular, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain. josepmaria.alegret@urv.cat.|Servei de Cardiologia, Hospital Universitari de Sant Joan, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili, c/Dr Josep Laporte, 1, 43204, Reus, Spain. josepmaria.alegret@urv.cat.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Alegret
mesh_terms: D000328:Adult; D001021:Aortic Valve / Q000002:abnormalities* / Q000473:pathology; D000082882:Bicuspid Aortic Valve Disease; D015331:Cohort Studies; D004108:Dilatation, Pathologic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006349:Heart Valve Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs
keywords: Aortic dilation; Bicuspid aortic valve; microRNA