Altered Lactylation Myocardial Tissue May Contribute to a More Severe Energy-Deprived State of the Tissue and Left Ventricular Outflow Tract Obstruction in HOCM

Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiovascular disease. In general, obstructive hypertrophic cardiomyopathy (HOCM) is more closely related to severe clinical symptoms and adverse clinical outcomes. Therefore, it is necessary to explore the possible causes of HOCM, which may help physicians better understand the disease and effectively control and manage the progression of the disease. In recent years, the discovery of lactylation has provided scholars with a new direction to explore the occurrence of diseases. In cardiovascular diseases, this post-translational modification can exacerbate cardiac dysfunction, and it can also promote the cardiac repair process after myocardial infarction. In this study, we used the myocardial tissue of mice carrying the <i>Myh7</i> V878A gene mutation site for protein lactylation detection. Through a further analysis of the enriched pathways using KEGG enrichment, GO enrichment, and Wiki Pathways enrichment, we found that the enriched pathways with lactylation modifications in the HOCM mice mainly included the fatty acid oxidation pathway, the tricarboxylic acid cycle pathway, the adrenergic signaling pathway in cardiomyocytes, and the cardiomyocyte hypertrophy pathway. Among the above pathways, significant changes in lactylation occurred in proteins including Acads, Acaa2, Mdh2, Myl2, and Myl3. We used the COIP experiment to verify the omics results and the ELISA assay to verify the function of the enzymes. We found that a decrease in lactylation modifications also led to a decrease in enzyme function. The abnormalities of these proteins not only lead to abnormalities in energy metabolism in the myocardial tissue of HOCM but also may affect myocardial contractility, resulting in the impaired contractile function of HOCM. The results of this study lay a preliminary theoretical foundation for further exploring the pathogenesis of HOCM.