Zheng Yue, Gao Wenqing, Zhang Qiang, Cheng Xian, Liu Yanwu, Qi Zhenchang, Li Tong
School of Medicine, Nankai University, Tianjin, China.
Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China.
Front Cardiovasc Med. 2022 Jun 30;9:906753. doi: 10.3389/fcvm.2022.906753. eCollection 2022.
Obesity plays an important role in type 2 diabetes mellitus (T2DM) and myocardial infarction (MI). Ferroptosis and ferritinophagy are related to metabolic pathways, such as fatty acid metabolism and mitochondrial respiration. We aimed to investigate the ferroptosis- and autophagy-related differentially expressed genes (DEGs) that might be potential targets for MI progression.
GSE116250 was analyzed to obtain DEGs. A Venn diagram was used to obtain the overlapping ferroptosis- and autophagy-related DEGs. The enrichment pathway analysis was performed and the hub genes were obtained. Pivotal miRNAs, transcription factors, and drugs with the hub genes interactions were also predicted. The MI mice model was constructed, and qPCR analysis and single-cell sequencing were used to validate the hub genes.
Utilizing the limma package and the Venn diagram, 26 ferroptosis-related and 29 autophagy-related DEGs were obtained. The list of ferroptosis-related DEGs was analyzed, which were involved in the cellular response to a toxic substance, cellular oxidant detoxification, and the IL-17 signaling pathway. The list of autophagy-related DEGs was involved in the regulation of autophagy, the regulation of JAK-STAT signaling pathway, and the regulation of MAPK cascade. In the protein-protein interaction network, the hub DEGs, such as IL-6, PTGS2, JUN, NQO1, NOS3, LEPR, NAMPT, CDKN2A, CDKN1A, and Snai1, were obtained. After validation using qPCR analysis in the MI mice model and single-cell sequencing, the 10 hub genes can be the potential targets for MI deterioration.
The screened hub genes, IL-6, PTGS2, JUN, NQO1, NOS3, LEPR, NAMPT, CDKN2A, CDKN1A, and Snai1, may be therapeutic targets for patients with MI and may prevent adverse cardiovascular events.
肥胖在2型糖尿病（T2DM）和心肌梗死（MI）中起重要作用。铁死亡和铁自噬与代谢途径相关，如脂肪酸代谢和线粒体呼吸。我们旨在研究可能是MI进展潜在靶点的铁死亡和自噬相关差异表达基因（DEGs）。
分析GSE116250以获得DEGs。使用维恩图获得重叠的铁死亡和自噬相关DEGs。进行富集通路分析并获得枢纽基因。还预测了与枢纽基因相互作用的关键miRNA、转录因子和药物。构建MI小鼠模型，并使用qPCR分析和单细胞测序验证枢纽基因。
利用limma软件包和维恩图，获得了26个铁死亡相关和29个自噬相关的DEGs。分析了铁死亡相关DEGs列表，其涉及对有毒物质的细胞反应、细胞氧化剂解毒和IL-17信号通路。自噬相关DEGs列表涉及自噬调节、JAK-STAT信号通路调节和MAPK级联调节。在蛋白质-蛋白质相互作用网络中，获得了枢纽DEGs，如IL-6、PTGS2、JUN、NQO1、NOS3、LEPR、NAMPT、CDKN2A、CDKN1A和Snai1。在MI小鼠模型中使用qPCR分析和单细胞测序进行验证后，这10个枢纽基因可能是MI恶化的潜在靶点。
筛选出的枢纽基因IL-6、PTGS2、JUN、NQO1、NOS3、LEPR、NAMPT、CDKN2A、CDKN1A和Snai1可能是MI患者的治疗靶点，并可能预防不良心血管事件。
