Lactylation associated biomarkers and immune infiltration in aortic dissection

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.