Patients with bicuspid and tricuspid aortic valve exhibit distinct regional microrna signatures in mildly dilated ascending aorta

被引:37
作者
Albinsson, Sebastian [1 ]
Della Corte, Alessandro [2 ]
Alajbegovic, Azra [1 ]
Krawczyk, Katarzyna K. [1 ]
Bancone, Ciro [2 ]
Galderisi, Umberto [3 ]
Cipollaro, Marilena [3 ]
De Feo, Marisa [2 ]
Forte, Amalia [3 ]
机构
[1] Lund Univ, Dept Expt Med Sci, Lund, Sweden
[2] Univ Naples 2, Dept Cardiothorac Sci, Naples, Italy
[3] Univ Naples Federico II, Dept Expt Med, Sect Biotechnol & Mol Biol, Via L De Crecchio 7, I-80138 Naples, Italy
基金
瑞典研究理事会;
关键词
Aortopathy; Ascending aorta; MicroRNAs; Mechanotransduction; Bicuspid aortic valve; SMOOTH-MUSCLE-CELLS; ANEURYSM DEVELOPMENT; AORTOPATHY; EXPRESSION; FIBROSIS; STRESS; GENES;
D O I
10.1007/s00380-016-0942-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-beta 1, 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.
引用
收藏
页码:750 / 767
页数:18
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