Li Yuan-Yuan, Zhang Sheng, Wang Hua, Zhang Shun-Xiao, Xu Ting, Chen Shu-Wen, Zhang Yan, Chen Yue
Department of Endocrinology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, People's Republic of China.
Pharmgenomics Pers Med. 2021 Feb 4;14:211-220. doi: 10.2147/PGPM.S281705. eCollection 2021.
Patients with diabetes have more calcification in atherosclerotic plaque and a higher occurrence of secondary cardiovascular events than patients without diabetes. The objective of this study was to identify crucial genes involved in the development of diabetic atherosclerotic plaque using a bioinformatics approach.
Microarray dataset GSE118481 was downloaded from the Gene Expression Omnibus (GEO) database; the dataset included 6 patients with diabetic atherosclerotic plaque (DBT) and 6 nondiabetic patients with atherosclerotic plaque (Ctrl). Differentially expressed genes (DEG) between the DBT and Ctrl groups were identified and then subjected to functional enrichment analysis. Based on the enriched pathways of DEGs, diabetic atherosclerotic plaque-related pathways were screened using the comparative toxicogenomics database (CTD). We then constructed a protein-protein interaction (PPI) network and transcription factor (TF)-miRNA-mRNA network.
A total of 243 DEGs were obtained in the DBT group compared with the Ctrl group, including 85 up-regulated and 158 down-regulated DEGs. Functional enrichment analysis showed that up-regulated DEGs were mainly enriched in isoprenoid metabolic process, DNA-binding TF activity, and response to virus. Additionally, DEGs participating in the toll-like receptor signaling pathway were closely related to diabetes, carotid stenosis, and insulin resistance. The TF-miRNA-mRNA network showed that toll-like receptor 4 (), BCL2-like 11 (), and glutamate-cysteine ligase catalytic subunit () were hub genes. Furthermore, was regulated by TF signal transducer and activator of transcription 6 (STAT6); was targeted by hsa-miR-24-3p; and was regulated by nuclear factor, erythroid 2 like 2 (NFE2L2).
Identification of hub genes and pathways increased our understanding of the molecular mechanisms underlying the atherosclerotic plaque in patients with or without diabetes. These crucial genes (, and ) might function as molecular biomarkers for diabetic atherosclerotic plaque.
与非糖尿病患者相比，糖尿病患者动脉粥样硬化斑块中的钙化更多，继发性心血管事件的发生率更高。本研究的目的是使用生物信息学方法鉴定参与糖尿病动脉粥样硬化斑块形成的关键基因。
从基因表达综合数据库（GEO）下载微阵列数据集GSE118481；该数据集包括6例糖尿病动脉粥样硬化斑块患者（DBT）和6例非糖尿病动脉粥样硬化斑块患者（对照组）。鉴定DBT组和对照组之间的差异表达基因（DEG），然后进行功能富集分析。基于DEG的富集途径，使用比较毒理基因组学数据库（CTD）筛选糖尿病动脉粥样硬化斑块相关途径。然后构建蛋白质-蛋白质相互作用（PPI）网络和转录因子（TF）-miRNA-mRNA网络。
与对照组相比，DBT组共获得243个DEG，包括85个上调DEG和158个下调DEG。功能富集分析表明，上调的DEG主要富集在类异戊二烯代谢过程、DNA结合TF活性和对病毒的反应中。此外，参与Toll样受体信号通路的DEG与糖尿病、颈动脉狭窄和胰岛素抵抗密切相关。TF-miRNA-mRNA网络显示，Toll样受体4（）、BCL2样11（）和谷氨酸-半胱氨酸连接酶催化亚基（）是枢纽基因。此外，由TF信号转导和转录激活因子6（STAT6）调节；被hsa-miR-24-3p靶向；并由核因子红细胞2样2（NFE2L2）调节。
枢纽基因和途径的鉴定增加了我们对糖尿病和非糖尿病患者动脉粥样硬化斑块潜在分子机制的理解。这些关键基因（、和）可能作为糖尿病动脉粥样硬化斑块的分子生物标志物。
