The Role of Macrophages in Atherosclerosis Development

Atherosclerosis is a chronic inflammatory vascular disease in which macrophages play central roles in lipid uptake, foam cell formation, plaque progression, plaque instability and, under certain conditions, plaque regression. This narrative review summarizes current knowledge on macrophage biology in atherosclerosis, with emphasis on macrophage phenotypic diversity, monocyte-endothelial interactions, foam cell formation, extracellular matrix remodeling, immune-cell interactions, cytokine signaling, mitochondrial dysfunction and cellular senescence. The review also discusses emerging macrophage-targeted strategies, including modulation of inflammatory activity, macrophage polarization, cholesterol efflux and lipid homeostasis. Although these approaches provide promising mechanistic and therapeutic insights, many remain at the preclinical stage. Further studies are needed to validate macrophage subtype-specific biomarkers, clarify the interaction between mitochondrial dysfunction and senescence, and evaluate safe and effective combination strategies for clinical translation.