Du Pei, Guo Ren, Gao Keqin, Yang Shuang, Yao Baige, Cui Haobo, Zhao Ming, Jia Sujie
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
Department of Dermatology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha 410013, Hunan, China.
Biosci Rep. 2021 Apr 30;41(4). doi: 10.1042/BSR20204124.
Coronary artery disease (CAD) is a chronic inflammatory disease caused by development of atherosclerosis (AS), which is the leading cause of mortality and disability. Our study aimed to identify the differentially expressed genes (DEGs) in CD14+ monocytes from CAD patients compared with those from non-CAD controls, which might pave the way to diagnosis and treatment for CAD.
The RNA-sequencing (RNA-seq) was performed by BGISEQ-500, followed by analyzing with R package to screening DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by R package. In addition, we validated the results of RNA-seq using real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, we explored the function of selected ten genes in LDL-treated CD14+ monocytes by RT-qPCR.
a total of 2897 DEGs were identified, including 753 up- and 2144 down-regulated genes in CD14+ monocytes from CAD patients. These DEGs were mainly enriched in plasma membrane and cell periphery of cell component, immune system process of biological process, NF-κB signaling pathway, cell adhesion molecules signaling pathway and cytokine-cytokine receptor interaction signaling pathway. In LDL-treated CD14+ monocytes, the mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) was significantly up-regulated.
In the present study, we suggested that PDK4 might play a role in progression of CAD. The study will provide some pieces of evidence to investigate the role and mechanism of key genes in the pathogenesis of CAD.
冠状动脉疾病（CAD）是一种由动脉粥样硬化（AS）发展引起的慢性炎症性疾病，AS是导致死亡和残疾的主要原因。我们的研究旨在鉴定CAD患者与非CAD对照者CD14+单核细胞中差异表达基因（DEG），这可能为CAD的诊断和治疗铺平道路。
通过BGISEQ-500进行RNA测序（RNA-seq），随后用R包进行分析以筛选DEG。用R包进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。此外，我们使用实时定量聚合酶链反应（RT-qPCR）验证RNA-seq结果。此外，我们通过RT-qPCR探索了所选的十个基因在低密度脂蛋白（LDL）处理的CD14+单核细胞中的功能。
共鉴定出2897个DEG，包括CAD患者CD14+单核细胞中753个上调基因和2144个下调基因。这些DEG主要富集在细胞成分的质膜和细胞周边、生物学过程的免疫系统过程、核因子κB（NF-κB）信号通路、细胞粘附分子信号通路和细胞因子-细胞因子受体相互作用信号通路。在LDL处理的CD14+单核细胞中，丙酮酸脱氢酶激酶4（PDK4）的mRNA表达显著上调。
在本研究中，我们认为PDK4可能在CAD进展中起作用。该研究将为研究关键基因在CAD发病机制中的作用和机制提供一些证据。
