Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
J Cardiovasc Pharmacol. 2018 May;71(5):275-282. doi: 10.1097/FJC.0000000000000568.
Abnormal expression of microRNAs (miRNAs) has been associated with aortic dissection (AD). Next-generation sequencing was performed to identify the differentially expressed miRNAs in aortic tissue samples between AD and nondiseased individuals. Selected miRNAs, which showed significant variation between the 2 groups, were then transfected into human aortic vascular smooth muscle cells, and assessed for effects on cell migration and induced apoptosis. The changes in gene expression pattern in human aortic vascular smooth muscle cells transfected with the miRNAs were also investigated. Among the 314 miRNAs detected in the aortic tissues from both AD and normal subjects, 46 showed significantly different expression patterns. Only 7 of these differentially expressed miRNAs were found to be enriched in AD, whereas the majority had diminished. hsa-miR-320d and hsa-miR-582 were 2 representative miRNAs that exhibited a decrease of greater than 10-fold. Transfection of hsa-miR-320d and hsa-miR-582 did not affect the migration capability of the vascular smooth muscle cells, but remarkably enhanced the staurosporine and tumor necrosis factor-α-induced apoptosis by 15% and 29%, respectively. Furthermore, the transfection of both miRNAs affected the expression of a vast multitude of genes, most of which were related to apoptotic pathways. The fluorescence reporter assays demonstrated that hsa-miR-320d and hsa-miR-582 bind the 3' UTR region of TRIAP1 and NET1 genes, respectively. These results suggest that hsa-miR-320d and hsa-miR-582 may serve as putative biomarkers for AD research.
异常表达的 microRNAs（miRNAs）与主动脉夹层（AD）有关。进行下一代测序以鉴定 AD 和非病变个体的主动脉组织样本中差异表达的 miRNAs。然后将显示两组之间存在显著差异的选定 miRNAs 转染到人主动脉血管平滑肌细胞中，并评估其对细胞迁移和诱导凋亡的影响。还研究了转染 miRNA 后人主动脉血管平滑肌细胞中基因表达模式的变化。在 AD 和正常受试者的主动脉组织中检测到的 314 个 miRNAs 中，有 46 个表现出明显不同的表达模式。这些差异表达的 miRNAs 中只有 7 个在 AD 中富集，而大多数则减少。hsa-miR-320d 和 hsa-miR-582 是表现出超过 10 倍下降的 2 个代表性 miRNAs。转染 hsa-miR-320d 和 hsa-miR-582 不会影响血管平滑肌细胞的迁移能力，但分别显著增强了 staurosporine 和肿瘤坏死因子-α诱导的凋亡 15%和 29%。此外，两种 miRNA 的转染均影响了大量基因的表达，其中大多数与凋亡途径有关。荧光报告测定表明 hsa-miR-320d 和 hsa-miR-582 分别结合 TRIAP1 和 NET1 基因的 3'UTR 区域。这些结果表明 hsa-miR-320d 和 hsa-miR-582 可能作为 AD 研究的潜在生物标志物。
