Post-Translational Protein Acylation in Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia and is strongly associated with stroke, heart failure, and mortality. Aging is a major risk factor, while atrial electrical, structural, and metabolic remodeling drive AF progression. Emerging evidence highlights protein lysine acylation as an important regulatory layer linking metabolism with epigenetic and signaling pathways in AF, including acetylation, propionylation, lactylation, 2-hydroxyisobutyrylation, succinylation, and malonylation. These modifications have been implicated in the regulation of ion channel activity, mitochondrial metabolism, oxidative stress, inflammation, and fibroblast activation, which may contribute to atrial remodeling and arrhythmogenesis. This review summarizes current advances in acylation-mediated mechanisms and discusses the potential therapeutic implications of modulating acylation-related enzymes, such as sirtuins, histone deacetylases, and acyltransferases. Understanding acylation regulatory networks may provide a basis for exploring acylation-associated biomarkers and therapeutic targets in AF.