Wang Jijuan, Wang Ping, Wang Weihua, Jin Huiling
Department of Cardiovascular Medicine, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Department of critical medicine, Shenzhen Hospital of Beijing University of traditional Chinese medicine (Longgang), Shenzhen, China.
J Thorac Dis. 2022 Aug;14(8):2987-2996. doi: 10.21037/jtd-22-1041.
Inflammation and immune cell infiltration in infarcted myocardial tissue are critical to myocardial infarction (MI) prognosis, and alterations in sphingolipid metabolism (SM) have been shown to potentially influence the inflammatory response and induce cardioprotection, but the underlying mechanisms are unclear. We therefore performed bioinformatics analysis to screen for key genes of SM in MI immune cells.
Three matrix files including GSE61145, GSE23294, and GSE71906 were downloaded from the Gene Expression Omnibus (GEO) database. GSE61145 was a human peripheral blood database, and GSE23294 and GSE71906 were 2 mouse myocardial tissue databases. R and annotation packages were used to screen for differentially-expressed genes (DEGs). Datasets of human and mouse cardiac tissues were downloaded from the GEO database for subsequent validation. The downloaded platform and matrix files were processed using R language and annotation packages. Key targets and enrichment pathways were identified using Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The Wilcoxon test was performed on the genes involved in SM pathways in neutrophils.
A total of 261 DEGs were obtained from human peripheral blood datasets, among which 101 were immune-related. GO analysis revealed that neutrophil activation, T cell activation, and T cell differentiation were significantly enriched in the immune-related DEGs. Three types of immune cells were identified in infarcted myocardial tissues. In addition, 194 DEGs were obtained from mouse myocardial tissue data, among which 6 SM-related genes (, , , , , and ) were significantly associated with MI. Evaluation of the relationships between these DEGs and neutrophils showed that the expression of the gene was significantly upregulated in neutrophils of the MI group, while the expression levels of the and genes were downregulated.
We identified 3 SM-related genes that were highly associated with neutrophils in MI, which may advance our understanding of SM in immune cells after MI.
梗死心肌组织中的炎症和免疫细胞浸润对心肌梗死（MI）的预后至关重要，鞘脂代谢（SM）的改变已被证明可能影响炎症反应并诱导心脏保护，但其潜在机制尚不清楚。因此，我们进行了生物信息学分析，以筛选MI免疫细胞中SM的关键基因。
从基因表达综合数据库（GEO）下载了三个矩阵文件，包括GSE61145、GSE23294和GSE71906。GSE61145是一个人类外周血数据库，GSE23294和GSE71906是两个小鼠心肌组织数据库。使用R和注释包筛选差异表达基因（DEG）。从GEO数据库下载人类和小鼠心脏组织的数据集用于后续验证。使用R语言和注释包对下载的平台和矩阵文件进行处理。使用基因本体（GO）术语富集和京都基因与基因组百科全书（KEGG）通路分析确定关键靶点和富集通路。对中性粒细胞中参与SM通路的基因进行Wilcoxon检验。
从人类外周血数据集中共获得261个DEG，其中101个与免疫相关。GO分析显示，中性粒细胞活化、T细胞活化和T细胞分化在免疫相关DEG中显著富集。在梗死心肌组织中鉴定出三种免疫细胞。此外，从小鼠心肌组织数据中获得194个DEG，其中6个与SM相关的基因（、、、、和）与MI显著相关。对这些DEG与中性粒细胞之间关系的评估表明，基因在MI组中性粒细胞中的表达显著上调，而基因和的表达水平下调。
我们鉴定出3个与MI中性粒细胞高度相关的SM相关基因，这可能增进我们对MI后免疫细胞中SM的理解。
