Zhu Dongfei, Zhang Xue, Fang Yuan, Xu Ziyang, Yu Yin, Zhang Lili, Yang YanPing, Li Shuai, Wang Yanpeng, Jiang Can, Huang Dong
The Department of Cardiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
The Department of Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Int J Biol Macromol. 2024 Dec;282(Pt 6):137431. doi: 10.1016/j.ijbiomac.2024.137431. Epub 2024 Nov 8.
Cardiovascular disease, particularly acute myocardial infarction (AMI), is a major global health concern. Current diagnostic methods for AMI lack sensitivity and specificity, necessitating novel biomarkers for early detection. In this study, we analyzed AMI gene expression datasets from the GEO database, employing Differential Gene Expression Analysis and WGCNA to identify key genes and co-expression modules. Lactylation-related genes (LRGs) from the MSigDB database were examined to identify those linked to AMI. Unsupervised consensus clustering classified AMI into subtypes, and machine learning models were developed for diagnosis. Immune cell infiltration was assessed using CIBERSORT, xCell, and MCPcounter, focusing on monocyte activation-related LRGs. We identified four LRGs (AMPD2, PYGL, SLC7A7, SAT1) significantly expressed in AMI, validated through in vitro experiments with primary cardiomyocytes from Sprague-Dawley rats. Our findings highlight LRGs as potential early AMI biomarkers and provide insights into myocardial repair mechanisms mediated by histone lactylation and monocytes.
心血管疾病,尤其是急性心肌梗死(AMI),是全球主要的健康问题。目前用于AMI的诊断方法缺乏敏感性和特异性,因此需要新的生物标志物用于早期检测。在本研究中,我们分析了来自GEO数据库的AMI基因表达数据集,采用差异基因表达分析和加权基因共表达网络分析(WGCNA)来识别关键基因和共表达模块。检查了来自MSigDB数据库的乳酸化相关基因(LRGs),以识别与AMI相关的基因。无监督一致性聚类将AMI分为不同亚型,并开发了机器学习模型用于诊断。使用CIBERSORT、xCell和MCPcounter评估免疫细胞浸润,重点关注与单核细胞激活相关的LRGs。我们鉴定出四个在AMI中显著表达的LRGs(AMPD2、PYGL、SLC7A7、SAT1),并通过对来自Sprague-Dawley大鼠的原代心肌细胞进行体外实验进行了验证。我们的研究结果突出了LRGs作为潜在的早期AMI生物标志物,并为组蛋白乳酸化和单核细胞介导的心肌修复机制提供了见解。