Targeting protein acylation modifications via SIRT1 and HDACs may mitigate myocardial injury and inflammationNew ways to treat heart failure through protein modifications

Cardiovascular diseases are the leading causes of death and disability worldwide. Their initiation and progression involve multiple complex processes, including metabolic disorders, oxidative stress, inflammatory responses, and cell death. Protein acylation, a rapidly advancing field in post-translational modification research, dynamically regulates protein function, chromatin status, and metabolic signaling networks by covalently attaching various acyl groups to specific protein sites, thereby serving as a key molecular mechanism linking cellular metabolic states to cardiovascular pathology. This review systematically summarizes the mechanisms of protein acylation modifications, including acetylation, lactylation, 2-hydroxyisobutyrylation, and palmitoylation—in major cardiovascular diseases such as cardiac hypertrophy and heart failure, atherosclerosis, myocardial ischemia-reperfusion injury, and arrhythmias. It also provides an overview of recent therapeutic strategies targeting SIRT1, HDACs, acetyl-CoA, Snail1, NLRP3, and Khib-associated metabolic enzymes. Accumulating evidence indicates that maintaining histone acetylation homeostasis, activating SIRT1, inhibiting HDACs, or intervening in specific acylation sites can effectively alleviate myocardial injury, suppress inflammatory responses, and improve cardiac remodeling and repair, offering new insights for mechanistic research and precision therapy of cardiovascular diseases.