Global Profiling of Protein Lysine Lactylation in Mouse Cardiac Hypertrophy: A Lactylome Analysis

Background: Cardiac hypertrophy, a major feature of heart failure, is closely linked to metabolic remodeling and energy deficiency. Lysine lactylation (Kla), a recently discovered post-translational modification (PTM), has been implicated in various cellular processes. However, its specific role in cardiac hypertrophy remains poorly understood. Methods: We conducted quantitative proteomics and Kla PTM analysis on left ventricular tissues from both sham-operated and aortic banding-induced hypertrophic mouse hearts. Protein samples were extracted, enriched for lactylation, and subjected to mass spectrometry. Bioinformatic analyses were performed to uncover pathways and protein–protein interactions (PPI) related to Kla-modified proteins. Results: Our lactylome analysis identified 159 Kla-modified sites across 80 proteins, with 72 proteins exhibiting elevated Kla levels, particularly in mitochondrial and sarcomeric proteins. Pathway enrichment analysis highlighted significant involvement of fatty acid metabolism, the tricarboxylic acid (TCA) cycle, and cardiomyopathy-related pathways, underscoring the role of Kla in energy metabolism and cardiac remodeling. PPI analysis further revealed the central role of metabolic and structural proteins in the hypertrophic response. Conclusions: Our study provides the comprehensive analysis of Kla in cardiac hypertrophy, revealing its significant role in modulating proteins involved in mitochondrial energy metabolism and sarcomeric structure. Our findings provide a comprehensive overview of the lactylation landscape in cardiac hypertrophy and reveal extensive lactylation changes in proteins associated with mitochondrial metabolism and sarcomeric organization. These observations suggest a potential link between Kla and cardiac hypertrophy, which warrants further functional investigation.