Li Xingda, He Xueqi, Zhang Yu, Hao Xinyuan, Xiong Anqi, Huang Jiayu, Jiang Biying, Tong Zaiyu, Huang Haiyan, Yi Lian, Chen Wenjia
National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education; International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy, Harbin Medical University, Harbin, 150086, Heilongjiang, People's Republic of China.
Department of Pharmacy at the Second Affiliated Hospital, and Department of Pharmacology at College of Pharmacy (The Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, 150086, People's Republic of China.
Sci Rep. 2025 Mar 26;15(1):10368. doi: 10.1038/s41598-025-94820-6.
This study investigated Hippo signaling pathway-related biomarkers in acute myocardial infarction (AMI). First, differentially expressed genes (DEGs) between AMI patients and controls were identified. Consensus clustering then classified AMI subtypes, followed by subtype-specific DEG screening. Candidate genes were derived from intersecting initial DEGs with subtype-associated DEGs. Three machine-learning algorithms prioritized five biomarkers (NAMPT, CXCL1, CREM, GIMAP6, and GIMAP7), validated through multi-dataset analyses and cellular expression profiling. qRT-PCR and Western blot confirmed differential expression patterns between AMI and controls across experimental models. Notably, NAMPT, CXCL1, and GIMAP6 exhibited cell-type-specific expression in endothelial cells and macrophages. We further predicted 179 potential therapeutic agents targeting these biomarkers. Niclosamide and eugenol were observed to mitigate hypoxia-induced injury in neonatal mouse ventricular cardiomyocytes. In vivo experiments demonstrated upregulated NAMPT/CXCL1 and downregulated GIMAP6/GIMAP7 in AMI myocardial tissues, with significant NAMPT protein elevation. These biomarkers show clinical diagnostic potential and provide mechanistic insights into AMI pathogenesis.
本研究调查了急性心肌梗死（AMI）中与河马信号通路相关的生物标志物。首先，确定了AMI患者与对照组之间的差异表达基因（DEG）。然后通过一致性聚类对AMI亚型进行分类，接着进行亚型特异性DEG筛选。候选基因来自初始DEG与亚型相关DEG的交集。三种机器学习算法对五个生物标志物（NAMPT、CXCL1、CREM、GIMAP6和GIMAP7）进行了优先级排序，并通过多数据集分析和细胞表达谱进行了验证。qRT-PCR和蛋白质印迹法证实了在不同实验模型中AMI与对照组之间的差异表达模式。值得注意的是，NAMPT、CXCL1和GIMAP6在内皮细胞和巨噬细胞中表现出细胞类型特异性表达。我们进一步预测了179种靶向这些生物标志物的潜在治疗药物。观察到氯硝柳胺和丁香酚可减轻新生小鼠心室心肌细胞的缺氧诱导损伤。体内实验表明，AMI心肌组织中NAMPT/CXCL1上调，GIMAP6/GIMAP7下调，NAMPT蛋白显著升高。这些生物标志物具有临床诊断潜力，并为AMI发病机制提供了机制性见解。
