Department of Stem Cell Biology, Atomic Bomb Diseases Institute, Nagasaki University, China.
Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Oxid Med Cell Longev. 2022 Apr 25;2022:5491038. doi: 10.1155/2022/5491038. eCollection 2022.
Atherosclerosis is the predominant cause of cardiovascular diseases. Existing studies suggest that the development of atherosclerosis is closely related to inflammation and immunity, but whether there are differences and similarities between atherosclerosis occurring at different sites is still unknown. We elucidated the pathological characteristics of peripheral vascular diseases by using bioinformatic analyses on immune cells and inflammation-related gene expression in atherosclerotic arteries and plaques.
Eight data sets regarding atherosclerosis were downloaded from the Gene Expression Omnibus database. Human immune genes were obtained from the IMMPORT website. The samples were scored and divided into high- and low-immune groups. Then the samples were analysed using weighted gene co-expression network analysis, while the modules were analysed using functional enrichment. The protein-protein interaction network was constructed using the STRING and Cytoscape databases. The hub immune genes were screened, and the correlation between hub immune genes and immune cells was analysed.
Immune cells and their functions were significantly different during atherosclerosis development. The infiltration proportion of immune cells was approximately similar in samples from different sources of patients with carotid atherosclerosis. However, the sensitivity of lower extremity atherosclerosis samples to immune cells is lower than that of carotid atherosclerosis samples.The samples from the plaque and artery were mainly infiltrated by macrophages, T cells and mast cells. After immune cells were assessed, resting NK cells, activated mast cells and M0 macrophages were found to be key immune cells in atherosclerosis and plaque formation. In addition, CCL4, TLR2, IL1B and PTPRC were considered to be immune marker genes in atherosclerosis development. Conclusion. Bioinformatic data analysis confirms the essential role of immune cells in cardiovascular diseases, and also indicates some differences of immune and inflammation characteristics of atherosclerosis between carotid and lower extremity arteries.
动脉粥样硬化是心血管疾病的主要病因。现有研究表明,动脉粥样硬化的发生发展与炎症和免疫密切相关,但不同部位发生的动脉粥样硬化在炎症和免疫方面是否存在差异尚不清楚。我们通过对动脉粥样硬化血管和斑块中的免疫细胞和炎症相关基因表达进行生物信息学分析,阐明了外周血管疾病的病理特征。
从基因表达综合数据库中下载了 8 个关于动脉粥样硬化的数据集。从 IMMPORT 网站获取人类免疫基因。根据评分将样本分为高免疫组和低免疫组。然后使用加权基因共表达网络分析对样本进行分析,同时使用功能富集对模块进行分析。使用 STRING 和 Cytoscape 数据库构建蛋白质-蛋白质相互作用网络。筛选出枢纽免疫基因,并分析枢纽免疫基因与免疫细胞之间的相关性。
在动脉粥样硬化的发生发展过程中,免疫细胞及其功能存在显著差异。不同来源的颈动脉粥样硬化患者样本中免疫细胞的浸润比例大致相似,但下肢动脉粥样硬化样本对免疫细胞的敏感性低于颈动脉粥样硬化样本。斑块和动脉的样本主要被巨噬细胞、T 细胞和肥大细胞浸润。对免疫细胞进行评估后,发现静息 NK 细胞、活化的肥大细胞和 M0 巨噬细胞是动脉粥样硬化和斑块形成的关键免疫细胞。此外,CCL4、TLR2、IL1B 和 PTPRC 被认为是动脉粥样硬化发生发展的免疫标志物基因。结论:生物信息学数据分析证实了免疫细胞在心血管疾病中的重要作用,同时也表明颈动脉和下肢动脉粥样硬化在炎症和免疫特征方面存在一些差异。