Ye Jianfeng, Fu Yuntao, Ke Yuanjia, Liu Huanting, Fang Sini, Lei Yumeng, Mao Ying, Yan Liqiu, Wang Youcheng
Department of Cardiology, The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, 523326, Guangdong, China.
Dongguan Key Laboratory of Cardiovascular Aging and Myocardial Regeneration, Dongguan Cardiovascular Research Institute, Dongguan, China.
Sci Rep. 2025 Jul 1;15(1):21536. doi: 10.1038/s41598-025-08613-y.
Protein lactylation, a novel post-translational modification (PTM), has emerged as a critical factor in disease processes related to glycolysis and immune responses. However, its role in aortic dissection (AD) has yet to be thoroughly investigated. This study aimed to investigate the involvement of protein lactylation in AD and identify key lactylation-related genes as potential diagnostic biomarkers. Transcriptomic data from public databases were analyzed to identify differentially expressed lactylation-related genes in AD. Functional enrichment analyses were performed, and Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to identify gene modules associated with AD. Machine learning methods, including LASSO and Random Forest, were employed to identify key diagnostic genes. Experimental validation was performed using human aortic tissues and an AD model. Bioinformatics analysis identified 11 lactylation-related differentially expressed genes (LR-DEGs) in AD. WGCNA and machine learning revealed two optimal feature genes, PGK1 and HMGA1, which were validated in an independent dataset and demonstrated high diagnostic accuracy (AUC: PGK1 = 1, HMGA1 = 0.94). Immune infiltration analysis indicated significant correlations between these genes and specific immune cell types, suggesting a role in immune regulation. Experimental validation in human and murine AD tissues confirmed the upregulation of PGK1 and HMGA1. This study underscores the importance of lactylation in the pathogenesis of AD and identifies PGK1 and HMGA1 as key biomarkers related to lactylation. These findings enhance our understanding of the metabolic and immune mechanisms involved in AD, thereby presenting new molecular targets for diagnosis and therapeutic intervention.
蛋白质乳酰化是一种新型的翻译后修饰(PTM),已成为与糖酵解和免疫反应相关的疾病过程中的关键因素。然而,其在主动脉夹层(AD)中的作用尚未得到充分研究。本研究旨在探讨蛋白质乳酰化在AD中的作用,并确定关键的乳酰化相关基因作为潜在的诊断生物标志物。分析公共数据库中的转录组数据,以确定AD中差异表达的乳酰化相关基因。进行功能富集分析,并利用加权基因共表达网络分析(WGCNA)来识别与AD相关的基因模块。采用包括套索回归(LASSO)和随机森林在内的机器学习方法来识别关键诊断基因。使用人主动脉组织和AD模型进行实验验证。生物信息学分析确定了AD中11个乳酰化相关差异表达基因(LR-DEGs)。WGCNA和机器学习揭示了两个最佳特征基因,即磷酸甘油酸激酶1(PGK1)和高迁移率族蛋白A1(HMGA1),它们在独立数据集中得到验证,并显示出高诊断准确性(曲线下面积:PGK1 = 1,HMGA1 = 0.94)。免疫浸润分析表明这些基因与特定免疫细胞类型之间存在显著相关性,提示其在免疫调节中的作用。在人和小鼠AD组织中的实验验证证实了PGK1和HMGA1的上调。本研究强调了乳酰化在AD发病机制中的重要性,并确定PGK1和HMGA1为与乳酰化相关的关键生物标志物。这些发现加深了我们对AD中代谢和免疫机制的理解,从而为诊断和治疗干预提供了新的分子靶点。