Gao Jing, Li Yuhong, Wang Tongmei, Shi Zhuo, Zhang Yiqi, Liu Shuang, Wen Pushuai, Ma Chunyan
a Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang 110001, China.
b Department of Ultrasonography, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
Can J Physiol Pharmacol. 2018 Aug;96(8):701-709. doi: 10.1139/cjpp-2017-0585. Epub 2018 Mar 6.
The aim of this study was to identify the key genes involved in the cardiac hypertrophy (CH) induced by pressure overload. mRNA microarray data sets GSE5500 and GSE18801 were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were screened using the Limma package; then, functional and pathway enrichment analysis were performed for common DEGs using the Database for Annotation, Visualization and Integrated Discovery database. Furthermore, the top DEGs were further validated using quantitative PCR in the hypertrophic heart tissue induced by isoprenaline. A total of 113 common DEGs with absolute fold change > 0.5, including 60 significantly upregulated DEGs and 53 downregulated DEGs, were obtained. Gene ontology term enrichment analysis suggested that common upregulated DEG were mainly enriched in neutrophil chemotaxis, extracellular fibril organization, and cell proliferation; and the common downregulated genes were significantly enriched in ion transport, endoplasmic reticulum, and dendritic spine. Kyoto Encyclopedia of Genes and Genomes pathway analysis found that the common DEGs were mainly enriched in extracellular matrix receptor interaction, phagosome, and focal adhesion. Additionally, the expression of Mfap4, Ltbp2, Aspn, Serpina3n, and Cnksr1 were upregulated in the model of CH, while the expression of Anp32a was downregulated. The current study identified the key deregulated genes and pathways involved in the CH, which could shed new light to understand the mechanism of CH.
本研究的目的是鉴定压力超负荷诱导的心肌肥大（CH）中涉及的关键基因。从基因表达综合数据库下载了mRNA微阵列数据集GSE5500和GSE18801，并使用Limma软件包筛选差异表达基因（DEG）；然后，使用注释、可视化和综合发现数据库对常见的DEG进行功能和通路富集分析。此外，使用定量PCR在异丙肾上腺素诱导的肥厚性心脏组织中进一步验证了排名靠前的DEG。共获得113个绝对变化倍数>0.5的常见DEG，包括60个显著上调的DEG和53个下调的DEG。基因本体术语富集分析表明，常见上调的DEG主要富集在中性粒细胞趋化、细胞外纤维组织和细胞增殖中；而常见下调基因则显著富集在离子转运、内质网和树突棘中。京都基因与基因组百科全书通路分析发现，常见的DEG主要富集在细胞外基质受体相互作用、吞噬体和粘着斑中。此外，在CH模型中，Mfap4、Ltbp2、Aspn、Serpina3n和Cnksr1的表达上调，而Anp32a的表达下调。本研究鉴定了CH中涉及的关键失调基因和通路，这可能为理解CH的机制提供新的线索。
