Vascular Immunometabolism in Atherosclerosis: Emerging Roles of Glycometabolic Reprogramming in Immune and Vascular...

The progression of atherosclerosis is closely associated with alterations in cellular glucose metabolism and vascular immunometabolic regulation. Increasing evidence indicates that glycometabolic reprogramming in macrophages, ECs, and vascular smooth muscle cells contributes to plaque development by modulating inflammatory activation, oxidative stress, lipid metabolism, and cellular phenotypic changes. In this review, we summarize recent advances in glycometabolic reprogramming during atherosclerosis, focusing on glycolysis, the pentose phosphate pathway, and lactate-mediated epigenetic regulation. We further discuss how metabolic alterations interact with immune responses, trained immunity, epigenetic remodeling, and cellular senescence to regulate the atherosclerotic microenvironment. In addition, we highlight potential therapeutic targets involved in metabolic regulation, including key glycolytic enzymes such as 6-phosphofructo-2-kinase and lactate dehydrogenase A, as well as metabolic-epigenetic pathways such as the TRAP1/HDAC3/H4K12la axis. However, significant challenges remain regarding cell-type specificity, therapeutic selectivity, and clinical translation of metabolic interventions. Understanding the complex relationship between glycometabolic reprogramming and vascular immunometabolism can provide mechanistic insights and guide future investigations of metabolic interventions for atherosclerosis.