Abstract
Atherosclerosis (AS) is a complex pathological process characterized by the pivotal involvement of foam cells in its pathogenesis. As the primary cellular components of arterial plaques, foam cells critically determine plaque stability. Foam cells derive mainly from macrophages, and their formation is driven by dysregulated lipid metabolism within these immune cells. Macrophage cholesterol metabolism is a highly regulated process comprising four key phases: uptake, esterification, hydrolysis, and efflux. Under physiological conditions, these four phases maintain a delicate balance. However, disruption of cholesterol homeostasis results in the excessive accumulation of intracellular lipid, promoting the formation of foam cell and inflammasome activation, thereby accelerating the atherosclerotic progression. Therefore, targeting macrophage cholesterol metabolism has emerged as a promising therapeutic approach for AS. This review summarizes the mechanisms underlying macrophage cholesterol metabolism and highlights recent progress in identifying bioactive components of traditional Chinese medicines (TCMs) that mitigate AS through the modulation of macrophage cholesterol homeostasis. These findings may offer novel insights into the development of clinically effective therapies for the prevention of AS.