Post-translational acylation of proteins in cardiac hypertrophy

Acylations are post-translational modifications in which functional groups are attached to amino acids on proteins. Most acylations (acetylation, butyrylation, crotonylation, lactylation, malonylation, propionylation and succinylation) involve lysine but cysteine (palmitoylation) and glycine (myristoylation) residues can also be altered. Acylations have important roles in physiological and pathophysiological processes, including cardiac hypertrophy and related cardiovascular diseases. These post-translational modifications influence chromatin architecture, transcriptional regulation and metabolic pathways, thereby affecting cardiomyocyte function and pathology. The dynamic interaction between these acylations and their regulatory enzymes, such as histone acetyltransferases, histone deacetylases and sirtuins, underscores the complexity of cellular homeostasis and pathological processes. Emerging evidence highlights the therapeutic potential of targeting acylations to modulate enzyme activity and metabolite levels, offering promising avenues for novel treatments. In this Review, we explore the diverse mechanisms through which acylations contribute to cardiac hypertrophy, highlighting the complexity and potential therapeutic targets in this regulatory network.