Protein lipidation in cardiovascular homeostasis, development, and disease

Protein lipidation is a posttranslational modification in which unique lipid moieties are covalently attached to proteins. These PTMs are critical for protein function, as they mediate intracellular membrane localization, facilitate protein-protein interactions, and regulate protein stability. Dynamic regulation of protein lipidation has emerged as an important regulatory mechanism influencing both cardiovascular physiology and disease. Several forms of protein lipidation, namely prenylation, S-acylation (e.g, palmitoylation), and N-myristoylation, are involved in many fundamental processes, including cardiovascular development, cardiac electrophysiology/contractility, blood pressure homeostasis, and angiogenesis. Moreover, aberrant protein lipidation is increasingly linked to a multitude of cardiovascular diseases such as cardiac hypertrophy, hypertension, atherosclerosis, and congenital heart disease. In the present review, we provide an overview of the different types of protein lipidation, the key enzymes that regulate these PTMs, and an in-depth discussion of the mechanisms by which protein lipidation contributes to cardiovascular physiology and disease.