Zhang Zheng, Chen Zhong
Department of Vascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Medicine (Baltimore). 2025 Jun 6;104(23):e42584. doi: 10.1097/MD.0000000000042584.
Atherosclerosis is characterized by chronic inflammation and plaque formation in arterial walls, accompanying by significant involvement of immune cells and mediators. Studies have demonstrated that factors, such as colony-stimulating factor-1, play critical roles in the development and exacerbation of these plaques, emphasizing the complexity of immune interactions in atherosclerosis. This study utilized GSE198600, GSE120521, GSE253903, and GSE224273 datasets to investigate the gene expression profiles and molecular mechanisms underlying atherosclerotic plaques. Differentially expressed genes were identified using DESeq2, followed by pathway analysis with clusterProfiler. Key hub genes were further explored through Cytoscape, and Mendelian randomization was performed using the TwoSampleMR package to assess genetic causality using ebi-a-GCST005840 and ebi-a-GCST006907 datasets. Finally, single-cell RNA sequencing data from GSE224273 and GSE253903 datasets were analyzed to characterize gene expression across various cell types in carotid atherosclerotic lesions. This study presented a comprehensive analysis of gene expression across various cell types in carotid atherosclerosis, highlighting the significant roles of key genes such as HMOX1, CD52, CSF1R, CD177, PTGDS, and TNC. HMOX1, primarily expressed in macrophages and dendritic cells, played a pivotal role in the immune response within atherosclerotic environments. CD52 and CSF1R, exhibiting high expression in immune cells, were implicated in modulating inflammatory processes crucial for plaque development and stability. CD177 and PTGDS emerged as top differentially expressed genes in symptomatic carotid plaques, linking them to critical biological processes, such as immune response and prostaglandin synthesis, which are essential for atherosclerosis progression. Similarly, TNC, a gene associated with extracellular matrix organization, showed significant upregulation in unstable plaque sections, underscoring its potential role in plaque destabilization and adverse cardiovascular events. These findings elucidated the complex cellular and molecular interactions in atherosclerosis, providing insights into potential therapeutic targets for preventing or treating atherosclerotic cardiovascular diseases. The differential expression of these genes across various cell types further emphasized the heterogeneity of the disease and the need for targeted approaches to effectively manage atherosclerosis.
动脉粥样硬化的特征是动脉壁出现慢性炎症和斑块形成，同时伴有免疫细胞和介质的大量参与。研究表明，集落刺激因子-1等因素在这些斑块的发展和恶化中起关键作用，这凸显了动脉粥样硬化中免疫相互作用的复杂性。本研究利用GSE198600、GSE120521、GSE253903和GSE224273数据集来研究动脉粥样硬化斑块的基因表达谱和分子机制。使用DESeq2鉴定差异表达基因，随后用clusterProfiler进行通路分析。通过Cytoscape进一步探索关键枢纽基因，并使用TwoSampleMR软件包进行孟德尔随机化，以利用ebi-a-GCST005840和ebi-a-GCST006907数据集评估遗传因果关系。最后，分析来自GSE224273和GSE253903数据集的单细胞RNA测序数据，以表征颈动脉粥样硬化病变中各种细胞类型的基因表达。本研究对颈动脉粥样硬化中各种细胞类型的基因表达进行了全面分析，突出了HMOX1、CD52、CSF1R、CD177、PTGDS和TNC等关键基因的重要作用。HMOX1主要在巨噬细胞和树突状细胞中表达，在动脉粥样硬化环境中的免疫反应中起关键作用。CD52和CSF1R在免疫细胞中高表达，与调节对斑块发展和稳定性至关重要的炎症过程有关。CD177和PTGDS是有症状颈动脉斑块中差异表达最显著的基因，将它们与免疫反应和前列腺素合成等关键生物学过程联系起来，这些过程对动脉粥样硬化进展至关重要。同样，TNC是一个与细胞外基质组织相关的基因，在不稳定斑块区域显著上调，突出了其在斑块不稳定和不良心血管事件中的潜在作用。这些发现阐明了动脉粥样硬化中复杂的细胞和分子相互作用，为预防或治疗动脉粥样硬化性心血管疾病的潜在治疗靶点提供了见解。这些基因在各种细胞类型中的差异表达进一步强调了该疾病的异质性以及采用针对性方法有效管理动脉粥样硬化的必要性。
