关键词: Bioinformatics Carotid atherosclerosis Endothelial dysfunction Hub genes Hypertension

来  源:   DOI:10.1016/j.heliyon.2024.e32966   PDF(Pubmed)

Abstract:
UNASSIGNED: Endothelial dysfunction is the early stage of carotid atherosclerosis (CAS) in patients with hypertension. It is worth identifying the potential hub genes of endothelial dysfunction to elucidate pathological mechanism in the progression of the disease.
UNASSIGNED: We obtained gene expression profiles of GSE43292 from the Gene Expression Omnibus (GEO) database. Hub genes associated with CAS were identified through weighted gene correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore potential biological mechanisms and signaling pathways. Finally, in vitro experiments on human umbilical vein endothelial cells (HUVECs) were conducted to validate these hub genes.
UNASSIGNED: The microarray dataset GSE43292 included 32 CAS plaques samples and corresponding macroscopically intact tissues from patients with hypertension. A total of 161 differentially expressed genes were discovered. Through WGCNA analysis, the gray60 module emerged as the most significant module associated with clinical features. The GO and KEGG enrichment analyses of genes in the gray60 module highlighted the substantial involvement of immune response-related signaling pathways. Two key hub genes (CCR1 and NCKAP1L) were pinpointed via LASSO regression. We found a significant increase in the mRNA expression level of the hub genes in oxidized low density lipoprotein (ox-LDL) treated HUVECs.
UNASSIGNED: Our study indicated that the hub genes related to immune responses are involved in the development of CAS. Two hub genes (CCR1 and NCKAP1L) of endothelial dysfunction were identified. These genes may provide a valuable therapeutic target of CAS in patients with hypertension.
摘要:
内皮功能障碍是高血压患者颈动脉粥样硬化(CAS)的早期阶段。确定内皮功能障碍的潜在hub基因以阐明疾病进展的病理机制是值得的。
我们从基因表达综合(GEO)数据库获得了GSE43292的基因表达谱。通过加权基因相关网络分析(WGCNA)和最小绝对收缩和选择算子(LASSO)回归鉴定与CAS相关的Hub基因。随后,进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析以探索潜在的生物学机制和信号通路。最后,在人脐静脉内皮细胞(HUVECs)上进行了体外实验以验证这些hub基因。
微阵列数据集GSE43292包括来自高血压患者的32个CAS斑块样品和相应的宏观完整组织。共发现161个差异表达基因。通过WGCNA分析,gray60模块是与临床特征相关的最重要模块.gray60模块中基因的GO和KEGG富集分析强调了免疫应答相关信号通路的实质性参与。通过LASSO回归确定了两个关键的hub基因(CCR1和NCKAP1L)。我们发现在氧化低密度脂蛋白(ox-LDL)处理的HUVEC中hub基因的mRNA表达水平显着增加。
我们的研究表明,与免疫反应相关的hub基因参与了CAS的发展。确定了内皮功能障碍的两个hub基因(CCR1和NCKAP1L)。这些基因可能为高血压患者的CAS提供有价值的治疗靶标。
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