Coarctation of the aorta (CoA) is a serious innate heart disease. Although surgery results are generally good, some complications such as recoarctation and aortic aneurysm or persistent hypertension were serious threats to patient’s health. To better understand the pathology of CoA and its underlying molecular mechanism is particularly important for early diagnosis and preventing the occurrence of its complications. However, the mechanisms of CoA remain unclear, especially for infants. RNA sequencing (RNA-seq) was used to identify the differentially expressed genes (DEGs) in vascular tissues of 12 patients with CoA and 10 normal participants form 3- to 34-month-old infants. The characteristic of DEGs were validated by quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and immunochemical staining (IHC) in vessels of patients with CoA and normal infants. A total of 2491 DEGs with the false discovery rate less than 0.05(> 1.5-fold, P < 0.05 change) were identified, including 443 upregulated genes and 2048 downregulated genes. The Gene Ontology enrichment analysis showed that 26 out of the 2491 DEGs identified were associated with cardiovascular diseases. These 26 genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs) differentiation. Three DEGs, that is, CNN1 (calponin), α-actinin1 and myosin heavy chain 11 MYH11, were validated using qRT-PCR and Western blot analysis. In addition, immunochemical staining showed that calponin and MYH11 were highly expressed on the surface and in the deep layers of the thickened intima respectively. This study comprehensively characterized the CoA transcriptome. Migration of extracellular matrix (ECM) and smooth muscle cells (SMCs) to the subendothelial space may be the major characteristic of CoA in infants.

中文翻译：

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主动脉缩窄婴儿患者的 RNA 测序分析


主动脉缩窄（CoA）是一种严重的先天性心脏病。虽然手术效果总体良好，但一些并发症如再缩、主动脉瘤或持续性高血压等严重威胁患者的健康。更好地了解CoA的病理学及其潜在的分子机制对于早期诊断和预防其并发症的发生尤为重要。然而，CoA 的机制仍不清楚，尤其是对于婴儿。使用 RNA 测序 (RNA-seq) 来鉴定 12 名 CoA 患者和 10 名 3 至 34 个月大婴儿的正常参与者血管组织中的差异表达基因 (DEG)。通过定量逆转录聚合酶链反应 (qRT-PCR) 和免疫化学染色 (IHC) 对 CoA 患者和正常婴儿的血管进行 DEG 的特征验证。共鉴定出2491个错误发现率小于0.05（>1.5倍，P<0.05变化）的DEG，其中上调基因443个，下调基因2048个。基因本体富集分析显示，在识别的 2491 个 DEG 中，有 26 个与心血管疾病相关。这 26 个基因主要与细胞外基质 (ECM) 和平滑肌细胞 (SMC) 分化相关。使用 qRT-PCR 和蛋白质印迹分析验证了三个 DEG，即 CNN1（钙调蛋白）、α-肌动蛋白1 和肌球蛋白重链 11 MYH11。此外，免疫化学染色显示，calponin和MYH11分别在增厚内膜表面和深层高表达。本研究全面表征了 CoA 转录组。 细胞外基质（ECM）和平滑肌细胞（SMC）向内皮下间隙的迁移可能是婴儿 CoA 的主要特征。