Shi Jing, Liu Hui, Wang Hui, Kong Xiangqing
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Biomed Res Int. 2016;2016:4682172. doi: 10.1155/2016/4682172. Epub 2016 Aug 4.
Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease.
退行性主动脉瓣狭窄,其特征为心脏左心室出口变窄,已成为老年人中最常见的心脏瓣膜病。本研究的目的是调查退行性主动脉瓣狭窄中的微小RNA(miRNA)特征。通过微阵列分析,我们确定了来自健康个体(n = 4)和退行性主动脉瓣狭窄患者(n = 4)的组织样本中的miRNA表达特征。在主动脉瓣狭窄患者的主动脉组织中,6种miRNA(hsa-miR-193a-3p、hsa-miR-29b-1-5p、hsa-miR-505-5p、hsa-miR-194-5p、hsa-miR-99b-3p和hsa-miR-200b-3p)过表达,14种(hsa-miR-3663-3p、hsa-miR-513a-5p、hsa-miR-146b-5p、hsa-miR-1972、hsa-miR-718、hsa-miR-3138、hsa-miR-21-5p、hsa-miR-630、hsa-miR-575、hsa-miR-301a-3p、hsa-miR-636、hsa-miR-34a-3p、hsa-miR-21-3p和hsa-miR-516a-5p)表达下调。使用GeneSpring 13.1通过比较TargetScan、PITA和microRNAorg数据库的预测进行三向比较来鉴定潜在的人类miRNA靶基因。进行基因本体(GO)和京都基因与基因组百科全书(KEGG)分析以鉴定与主动脉瓣狭窄相关的潜在途径和功能注释。在主动脉瓣狭窄患者样本和正常对照之间,20种miRNA有显著差异表达,并确定了与这种疾病相关的潜在miRNA靶标和分子途径。本研究描述了退行性主动脉瓣狭窄中的miRNA表达特征,并增进了对该疾病分子病理生物学的理解。