Department of ICU, The Fourth Hospital of Hebei Medical University, Shijiazhuang, PR China.
Clinical School of Thoracic, Tianjin Medical University, Tianjin, PR China.
Medicine (Baltimore). 2023 Nov 17;102(46):e36133. doi: 10.1097/MD.0000000000036133.
Atherosclerosis is a chronic disease that thickens the blood vessel walls and narrows the lumen. Venous thrombosis is a blood clot that forms in the body's deep veins or pulmonary arteries. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and venous thrombosis is unclear. We employed data files that combined atherosclerosis and chronic stress groups. Subsequently, we conducted differential gene expression analysis (DEGs) and performed weighted gene co-expression network analysis (WGCNA). We constructed and analyzed a protein-protein interaction (PPI) network. Further analyses included functional enrichment analysis, gene set enrichment analysis (GSEA), gene expression heatmaps, immune infiltration analysis, and mRNA analysis. By comparing our findings with the Comparative Toxicogenomics Database (CTD), we identified the most relevant diseases associated with the core genes. Additionally, we utilized TargetScan to screen for miRNAs regulating the central DEGs. To validate our results, we conducted Western Blot experiments at the cellular level. A total of 1747 DEGs were co-identified. According to the Gene Ontology (GO) analysis of differentially expressed genes, they were primarily enriched in mitochondrial gene expression, mitochondrial envelope, organelle membrane, and mitochondrial inner membrane categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target cells were mainly enriched in metabolic pathways, ribosomes, and histidine metabolism. The intersection of enriched terms from both GO and KEGG analyses showed significant enrichment in mitochondrial gene expression, mitochondrial envelope, organelle inner membrane, ribosomal structural constituents, histidine metabolism, and oxidative phosphorylation. Eight core genes were identified, including NDUFS5, UQCRQ, COX6C, COX7B, ATP5ME, NDUFS3, NDUFA3, and NDUFB11. The gene expression heatmap demonstrated that core genes (NDUFB11 and NDUFS3) were downregulated in atherosclerosis with venous thrombosis samples and upregulated in normal samples. CTD analysis revealed that the core genes NDUFB11 and NDUFS3 were associated with pain, arterial diseases, atherosclerosis, arteritis, venous thrombosis formation, and venous thromboembolism. We added Western Blot basic cell experiment for verification. NDUFB11 and NDUFS3 are downregulated in atherosclerosis and venous thrombosis, associated with poorer prognosis, and may serve as potential biomarkers for both diseases.
动脉粥样硬化是一种使血管壁变厚并使管腔变窄的慢性疾病。静脉血栓形成是指在身体深部静脉或肺动脉中形成的血凝块。然而，NDUFB11 和 NDUFS3 与动脉粥样硬化和静脉血栓形成之间的关系尚不清楚。我们使用了结合动脉粥样硬化和慢性应激组的数据集。随后，我们进行了差异基因表达分析（DEGs）和加权基因共表达网络分析（WGCNA）。我们构建和分析了蛋白质-蛋白质相互作用（PPI）网络。进一步的分析包括功能富集分析、基因集富集分析（GSEA）、基因表达热图、免疫浸润分析和 mRNA 分析。通过将我们的发现与比较毒理学基因组数据库（CTD）进行比较，我们确定了与核心基因最相关的疾病。此外，我们利用 TargetScan 筛选调节中心 DEGs 的 miRNAs。为了验证我们的结果，我们在细胞水平上进行了 Western Blot 实验。总共鉴定出 1747 个差异表达基因。根据差异表达基因的基因本体论（GO）分析，它们主要富集在线粒体基因表达、线粒体包膜、细胞器膜和线粒体内膜类别中。京都基因与基因组百科全书（KEGG）分析表明，靶细胞主要富集在代谢途径、核糖体和组氨酸代谢中。GO 和 KEGG 分析中富集术语的交集表明，在线粒体基因表达、线粒体包膜、细胞器内膜、核糖体结构成分、组氨酸代谢和氧化磷酸化中存在显著富集。确定了 8 个核心基因，包括 NDUFS5、UQCRQ、COX6C、COX7B、ATP5ME、NDUFS3、NDUFA3 和 NDUFB11。基因表达热图表明，核心基因（NDUFB11 和 NDUFS3）在动脉粥样硬化伴静脉血栓形成样本中下调，在正常样本中上调。CTD 分析表明，核心基因 NDUFB11 和 NDUFS3 与疼痛、动脉疾病、动脉粥样硬化、动脉炎、静脉血栓形成和静脉血栓栓塞相关。我们添加了 Western Blot 基本细胞实验进行验证。NDUFB11 和 NDUFS3 在动脉粥样硬化和静脉血栓形成中下调，与预后较差相关，可能成为这两种疾病的潜在生物标志物。
