Lactylation, Crotonylation and Succinylation: Decoding Their Roles in the Progression of Cardiovascular Disease

Cardiovascular diseases (CVDs), such as atherosclerosis, myocardial remodeling, myocardial ischemia-reperfusion (I/R) injury, heart failure, and oxidative stress, are among the greatest threats to human health globally. The molecular mechanisms underlying CVDs have not yet been fully elucidated, but progress has been made in research on epigenetics in CVDs. Post-translational modifications (PTMs), which involve the covalent attachment of functional groups to modulate protein structure and function, represent a critical regulatory mechanism. These modifications enhance the functional diversity of the proteome without the need for de novo protein synthesis. Traditional types of PTMs, such as phosphorylation, acetylation, and ubiquitination, are closely associated with the pathogenesis of CVDs. With the application of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), an increasing number of novel acylation modifications have been discovered, including propionylation, butylation, crotonylation, succinylation, lactylation, and isonicotinylation. A deeper understanding of the role of PTMs in CVDs is essential for unraveling their molecular regulatory mechanisms and identifying new biomarkers and therapeutic targets. This review summarizes the mechanisms related to the occurrence and development of CVDs associated with three novel acylation modifications: crotonylation, lactylation, and succinylation.