Identification of potential hub genes and regulatory networks of smoking-related endothelial dysfunction in atherosclerosis using bioinformatics analysis
机构：[1]Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.外科系统血管外科首都医科大学宣武医院[2]Department of Intensive Care Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.首都医科大学宣武医院
Endothelial dysfunction, the earliest stage of atherosclerosis, can be caused by smoking, but its molecular mechanism requires further investigation.This study aimed to use bioinformatics analysis to identify potential mechanisms involved in smoking-related atherosclerotic endothelial dysfunction.The transcriptome data used for this bioinformatics analysis were obtained from the Gene Expression Omnibus (GEO) database. The GSE137578 and GSE141136 datasets were used to identify common differentially expressed genes (co-DEGs) in endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) and tobacco. The co-DEGs were annotated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) databases. Additionally, a protein-protein interaction (PPI) network was constructed to visualize their interactions and screen for hub genes. GSE120521 dataset was used to verify the expression of hub genes in unstable plaques. The miRNA expression profile GSE137580 and online databases (starBase 2.0, TargetScan 8.0 and DGIdb v4.2.0) were used to predict the related non-coding RNAs and drugs.A total of 232 co-DEGs were identified, including 113 up-regulated genes and 119 down-regulated genes. These DEGs were primarily enriched in detrimental autophagy, cell death, transcription factors, and cytokines, and were implicated in ferroptosis, abnormal lipid metabolism, inflammation, and oxidative stress pathways. Ten hub genes were screened from the constructed PPI network, including up-regulated genes such as FOS, HMOX1, SQSTM1, PTGS2, ATF3, DDIT3, and down-regulated genes MCM4, KIF15, UHRF1, and CCL2. Importantly, HMOX1 was further up-regulated in unstable plaques (p= 0.034). Finally, a regulatory network involving lncRNA/circRNA-miRNA-hub genes and drug-hub genes was established.Atherosclerotic endothelial dysfunction is associated with smoking-induced injury. Through bioinformatics analysis, we identified potential mechanisms and provided potential therapeutic targets.
基金：
This study was supported by the National Key Research and Development Program of China (No.2021YFC2500500).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|4 区医学
小类|4 区工程：生物医学4 区卫生保健与服务
最新[2023]版：
大类|4 区医学
小类|4 区工程：生物医学4 区卫生保健与服务
JCR分区：
出版当年[2022]版：
Q4ENGINEERING, BIOMEDICALQ4HEALTH CARE SCIENCES & SERVICES
最新[2023]版：
Q3HEALTH CARE SCIENCES & SERVICESQ4ENGINEERING, BIOMEDICAL
第一作者机构：[1]Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
通讯作者：
通讯机构：[1]Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.[*1]Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China
推荐引用方式(GB/T 7714)：
Guo Julong,Ning Yachan,Pan Dikang,et al.Identification of potential hub genes and regulatory networks of smoking-related endothelial dysfunction in atherosclerosis using bioinformatics analysis[J].TECHNOLOGY AND HEALTH CARE.2024,32(3):1781-1794.doi:10.3233/THC-230796.
APA：
Guo Julong,Ning Yachan,Pan Dikang,Wu Sensen,Gao Xixiang...&Gu Yongquan.(2024).Identification of potential hub genes and regulatory networks of smoking-related endothelial dysfunction in atherosclerosis using bioinformatics analysis.TECHNOLOGY AND HEALTH CARE,32,(3)
MLA：
Guo Julong,et al."Identification of potential hub genes and regulatory networks of smoking-related endothelial dysfunction in atherosclerosis using bioinformatics analysis".TECHNOLOGY AND HEALTH CARE 32..3(2024):1781-1794
