Distinct types of protein modifications in diabetic endothelial dysfunction

Diabetes mellitus is a metabolic disorder characterized by persistent hyperglycemia. Chronic diabetes mellitus may contribute to endothelial dysfunction and result in various conditions such as diabetic retinopathy, diabetic nephropathy, neuropathy, peripheral vascular disease, and metabolic syndrome. Post-translational modifications (PTMs) refer to the chemical alterations made to amino acid residues on post-translational proteins, achieved through the addition or removal of specific functional groups. These modifications significantly influence a protein's structure and dynamics, ultimately regulating its localization, folding, interactions with other biomolecules, and overall activity, including mitochondrial function, insulin secretion, cellular development, and viability. The present review aims to provide a comprehensive overview of the different types of PTMs associated with diabetic endothelial dysfunction, including glycosylation, ubiquitination, phosphorylation, acetylation, lactylation, palmitoylation, SUMOylation, methylation, carbonylation, and other PTMs. Currently, several drugs and compounds have been found to improve endothelial cell function in diabetes mellitus by targeting PTMs. By elucidating the mechanisms through which these modifications contribute to endothelial dysfunction in diabetes, this review aspires to enhance the understanding of the condition and potentially facilitate the development of innovative therapeutic strategies aimed at addressing cardiovascular complications in individuals with diabetes.