急性ST段抬高型心肌梗死患者Th17细胞的转录组分析

Transcriptome analysis of Th17 cells in ST-elevation myocardial infarction

目的检测急性ST段抬高型心肌梗死(ST-elevation myocardial infarction, STEMI)早期外周血Th17细胞的基因表达谱,揭示Th17细胞在STEMI后的活化和功能。方法收集STEMI患者的的外周血Th17细胞转录组测序及分析,并通过实时定量RT-PCR验证基因的差异表达。结果与正常人相比,STEMI患者的外周血的CD45RA-CCR6+CCR4+CXCR3-Th17细胞约30%的上调基因与细胞代谢有关,其中与三羧酸循环、氧化磷酸化和电子呼吸链相关的基因表达明显上调,而与糖酵解相关的基因表达则无明显上调。前10个与代谢有关的高表达基因中Pdha1、Fh1、Cs、Mdh1和Aco1编码参与三羧酸循环的蛋白;而Cox10、Nd3、Ndufa1和Cox1编码参与氧化磷酸化的蛋白。结论 Th17细胞在STEMI发生后的细胞代谢活动显著增强,可能为其参与心梗后的急性炎症反应提供能量基础。

The current study was designed to reveal the activation status and functional features of Th17 cells in acute ST-elevation myocardial infarction(STEMI) by characterizing the gene expression profile of blood Th17 cells in STEMI. Blood Th17 cells were harvested from STEMI patients and subjected to transcriptome sequencing and gene expression analysis. The differentially expressed genes(DEGs) were identified and validated by real-time RT-PCR. We found that in comparison with the samples from healthy people, about 30% of the up-regulated genes in CD45RA-CCR6+CCR4+CXCR3-Th17 cells of STEMI patients were related to metabolism. In particular, the genes encoding the proteins that participate in the tricarboxylic acid cycle, oxidative phosphorylation, and electron transport chain were significantly up-regulated in STEMI Th17 cells, while the expression of glycolysis-related genes were not changed. Among the top 10 up-regulated metabolic genes, Pdha1, Fh1, Cs, Mdh1, and Aco1 were related to proteins in tricarboxylic acid cycle, while Cox10, Nd3, Ndufa1, and Cox1 encode proteins related to oxidative phosphorylation. Therefore, the promoted metabolic activity might offer enough energy to Th17 cells to fuel the inflammation after STEMI.