Department of Cardio-thoracis Surgery, Zhejiang Hospital, Hangzhou, Zhejiang, China.
Bioengineered. 2021 Dec;12(1):7950-7963. doi: 10.1080/21655979.2021.1984004.
Acute myocardial infarction (AMI) tends to cause severe heart failure and the population suffering from AMI gradually become younger. This study aims to determine the key genes associated with AMI, ferroptosis and hypoxia that could serve as novel biomarkers for AMI. There were 522 up-regulated genes and 119 down-regulated genes in GSE4648. Based on the expression of ferroptosis-related genes (FRGs) and hypoxia-related genes, the ferroptosis Z-score and the hypoxia Z-score calculated by ssGSEA were significantly higher in the infarcted area of AMI mice than in the control group, and there was a positive correlation between ferroptosis and hypoxia Z-score. 6 modules were obtained by Weighted Gene Co-Expression Network Analysis (WGCNA), and 2 key modules and 66 key genes were screened out. Genes in the key modules were found mainly related to ERK1 and ERK2 cascade, TNF signaling pathway, and MAPK signaling pathway through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Protein-protein interaction (PPI) network analysis was performed on the key genes and 10 hub genes (, and ) were obtained using STRING and Cytohubba. The expression of 9 hub genes except was consistent in GSE4648 and GSE775. The transcription factors (TFs)-hub genes interaction network was constructed and 48 TFs were obtained using TRRUST. Finally, it was verified through the animal experiment that these hub genes were up-regulated in AMI mice myocardial tissues. This study offers new ideas for the diagnosis and treatment of AMI.
急性心肌梗死（AMI）往往会导致严重的心衰，且患 AMI 的人群逐渐年轻化。本研究旨在确定与 AMI、铁死亡和缺氧相关的关键基因，这些基因可能成为 AMI 的新型生物标志物。在 GSE4648 中，有 522 个上调基因和 119 个下调基因。基于铁死亡相关基因（FRGs）和缺氧相关基因的表达，ssGSEA 计算的 AMI 小鼠梗死区的铁死亡 Z 值和缺氧 Z 值明显高于对照组，且铁死亡和缺氧 Z 值呈正相关。通过加权基因共表达网络分析（WGCNA）得到 6 个模块，筛选出 2 个关键模块和 66 个关键基因。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析发现，关键模块中的基因主要与 ERK1 和 ERK2 级联、TNF 信号通路和 MAPK 信号通路有关。对关键基因进行蛋白质-蛋白质相互作用（PPI）网络分析，使用 STRING 和 Cytohubba 获得 10 个枢纽基因（、和）。除 外，其余 9 个枢纽基因在 GSE4648 和 GSE775 中的表达一致。构建转录因子（TFs）-枢纽基因互作网络，使用 TRRUST 获得 48 个 TF。最后，通过动物实验验证这些枢纽基因在 AMI 小鼠心肌组织中上调。本研究为 AMI 的诊断和治疗提供了新的思路。
