The Role and Research Progress of Glycolytic Metabolic Reprogramming in Smooth Muscle Cells in Atherosclerosis

Atherosclerosis(AS) is a chronic vascular disease resulting from the combined effects of lipid deposition and inflammatory responses, in which the phenotypic plasticity of vascular smooth muscle cells (VSMCs) plays a central role in disease progression. Under aerobic conditions, VSMCs undergo a metabolic shift reminiscent of the "Warburg effect", supporting their proliferation, migration, and phenotypic modulation through enhanced glycolytic flux. Despite its pathophysiological significance, the mechanistic interplay between glycolytic reprogramming in VSMCs and atherosclerotic progression remains inadequately systematized. This review aims to bridge this knowledge gap by synthesizing emerging evidence on how glycolysis orchestrates VSMCs remodeling and contributes to the clinical manifestations of AS. Furthermore, we explore the synergistic coupling between glycolytic metabolism and electrophysiological dynamics in VSMCs-an emerging area with transformative potential. Our methodology integrates multidimensional strategies: first, we delineate the metabolic drivers of VSMCs phenotypic switching in AS; second, we combine in vitro and in vivo models to elucidate the role of VSMCs glycolysis in diabetes-accelerated AS and in-stent restenosis; lastly, we investigate metaboloelectrophysiological crosstalk and ion channel regulation as central mechanisms. This synthesis provides a conceptual and mechanistic foundation for targeting glycolytic pathways in AS and its complications, offering novel avenues for therapeutic intervention.