PDF(Pubmed)
Abstract：
Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End-MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632-driven End-MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End-MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End-MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients\' blood. Our findings definitively demonstrate that the End-MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.
摘要：
胸主动脉瘤（TAA）是一个严重的健康问题，因为它们与早期主动脉夹层和破裂有关。TAA的形成是由遗传条件引发的，特别是马凡氏综合征（MFS）和二尖瓣主动脉瓣（BAV）。在动脉瘤过程中，主动脉内皮细胞可以经历内皮-间质转化（End-MT），随后发生表型和功能改变。我们先前记录了MFSTAA的特征是miR-632驱动的End-MT恶化，而在BAV主动脉病变中，这一过程的发生仍然存在争议。我们调查了BAV的End-MT过程和强调的调控机制，TAV和MFSTAA组织。进行基因表达和免疫组织化学分析以分析表征End-MT的一些重要miRNA和基因。我们记录了BAV内皮维持内皮稳态标志物的表达，如ERG，CD31和miR-126-5p,与MFS相比，它显示较低水平的miR-632和间充质标志物。有趣的是,我们还发现MFS患者血液中miR-632水平较高.我们的研究结果明确表明，End-MT流程并没有描述BAV的特征，在其他TAA中，更好地保持内皮特征。此外,我们的结果表明miR-632是MFS主动脉病变的一个有前景的诊断/预后因子.
