title: Patients with bicuspid and tricuspid aortic valve exhibit distinct regional microrna signatures in mildly dilated ascending aorta.
abstract: MicroRNAs are able to modulate gene expression in a range of diseases. We focused on microRNAs as potential contributors to the pathogenesis of ascending aorta (AA) dilatation in patients with stenotic tricuspid (TAV) or bicuspid aortic valve (BAV). Aortic specimens were collected from the 'concavity' and the 'convexity' of mildly dilated AAs and of normal AAs from heart transplant donors. Aortic RNA was analyzed through PCR arrays, profiling the expression of 84 microRNAs involved in cardiovascular disease. An in silico analysis identified the potential microRNA-mRNA interactions and the enriched KEGG pathways potentially affected by microRNA changes in dilated AAs. Distinct signatures of differentially expressed microRNAs are evident in TAV and BAV patients vs. donors, as well as differences between aortic concavity and convexity in patients only. MicroRNA changes suggest a switch of SMC phenotype, with particular reference to TAV concavity. MicroRNA changes potentially affecting mechanotransduction pathways exhibit a higher prevalence in BAV convexity and in TAV concavity, with particular reference to TGF-β1, Hippo, and PI3K/Akt/FoxO pathways. Actin cytoskeleton emerges as potentially affected by microRNA changes in BAV convexity only. MicroRNAs could play distinct roles in BAV and TAV aortopathy, with possible implications in diagnosis and therapy.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Albinsson
authors.affiliation: Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Della Corte
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Azra
authors.initials: A
authors.lastname: Alajbegovic
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Katarzyna K
authors.initials: KK
authors.lastname: Krawczyk
authors.affiliation: Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Bancone
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, Second University of Naples, Via L De Crecchio, 7, 80138, Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, Second University of Naples, Via L De Crecchio, 7, 80138, Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Cipollaro
authors.affiliation: Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: De Feo
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, Second University of Naples, Via L De Crecchio, 7, 80138, Naples, Italy. amalia.forte@unina2.it.
authors.forename: Amalia
authors.identifier: http://orcid.org/0000-0002-9652-3249
authors.initials: A
authors.lastname: Forte
mesh_terms: D000328:Adult; D000368:Aged; D001011:Aorta / Q000473:pathology*; D001021:Aortic Valve / Q000002:abnormalities / Q000473:pathology*; D016022:Case-Control Studies; D004108:Dilatation, Pathologic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006349:Heart Valve Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D040542:Mechanotransduction, Cellular; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D014261:Tricuspid Valve / Q000473:pathology
chemical_list: D035683:MicroRNAs
keywords: Aortopathy; Ascending aorta; Bicuspid aortic valve; Mechanotransduction; MicroRNAs