Molecular mechanisms, crosstalk and therapeutic potential of novel acylation modifications in cardiovascular and cerebrovascular diseases.

Metabolic reprogramming, the fundamental process by which cells adapt to fluctuations in energy demands, is pivotal in the pathophysiology of cardiovascular and cerebrovascular diseases (CCVDs). Aberrant reprogramming of glucose, lipid, and amino acid metabolism is intricately associated with pathological processes in CCVDs such as cardiac hypertrophy, atherosclerosis, and ischemia-reperfusion injury. This metabolic remodeling disrupts the dynamic balance of metabolites (cc, acetyl-CoA and lactate) in the cardio-cerebrovascular systems, thereby inducing abnormal post-translational modifications (PTMs) on histones and non-histone proteins. These PTMs drive disease progression by modulating gene transcription or the activity of key proteins, which subsequently influences downstream signaling pathways. Here, we systematically examine the regulatory enzymes and functional roles of nine recently characterized acylation modifications: crotonylation, β-hydroxybutyrylation, 2-hydroxyisobutyrylation, succinylation, malonylation, glutarylation, lactylation, propionylation, and butyrylation. Furthermore, this review elaborates on the molecular mechanisms, crosstalk and the latest preclinical advancements regarding these acylations in CCVDs, emphasizing the influence of distinct acylation patterns on various pathological processes and highlighting the clinical translational prospects of targeting these novel modifications for therapeutic intervention.