Albinsson Sebastian, Della Corte Alessandro, Alajbegovic Azra, Krawczyk Katarzyna K, Bancone Ciro, Galderisi Umberto, Cipollaro Marilena, De Feo Marisa, Forte Amalia
Department of Experimental Medical Science, Lund University, Lund, Sweden.
Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy.
Heart Vessels. 2017 Jun;32(6):750-767. doi: 10.1007/s00380-016-0942-7. Epub 2017 Jan 19.
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.
微小RNA能够调节一系列疾病中的基因表达。我们聚焦于微小RNA,其可能是狭窄三尖瓣(TAV)或二叶式主动脉瓣(BAV)患者升主动脉(AA)扩张发病机制的促成因素。从轻度扩张的升主动脉的“凹面”和“凸面”以及心脏移植供体的正常升主动脉中采集主动脉标本。通过PCR阵列分析主动脉RNA,分析84种参与心血管疾病的微小RNA的表达情况。计算机分析确定了潜在的微小RNA-信使核糖核酸相互作用以及扩张升主动脉中微小RNA变化可能影响的富集KEGG通路。在TAV和BAV患者与供体之间,以及仅在患者的主动脉凹面和凸面之间,差异表达的微小RNA具有明显的特征。微小RNA的变化表明平滑肌细胞表型发生了转变,特别是在TAV凹面。可能影响机械转导通路的微小RNA变化在BAV凸面和TAV凹面更为普遍,特别是涉及转化生长因子-β1、Hippo和PI3K/Akt/FoxO通路。肌动蛋白细胞骨架仅在BAV凸面可能受微小RNA变化的影响。微小RNA可能在BAV和TAV主动脉病变中发挥不同作用,对诊断和治疗可能具有重要意义。