Phytochemicals alter foam cell formation and macrophage cholesterol efflux

The accumulation of cholesterol within arterial macrophages, resulting from disrupted processes of cholesterol uptake, esterification, and efflux, is a critical factor in foam cell formation and the pathogenesis of atherosclerosis. Dysregulation of cholesterol homeostasis—marked by increased scavenger receptor-mediated uptake of cholesterol or oxidized low-density lipoprotein (ox-LDL) via receptors such as LOX-1, CD36, and SR-A, elevated expression of cholesterol acyltransferase-1 (ACAT1), and diminished cholesterol efflux mediated by ATP-binding cassette (ABC) transporters including ABCA1, ABCG1, and SR-BI—facilitates the development of macrophage foam cells. These lipid-enriched cells play a pivotal role in the progression, destabilization, and rupture of atherosclerotic plaques. Epidemiological studies suggest that phytochemicals derived from plant-based diets—bioactive compounds encompassing phenolics, terpenoids, alkaloids, nitrogen-containing compounds, phytosterols, and non-starch polysaccharides—exert significant regulatory effects on macrophage foam cell formation by inhibiting cholesterol uptake and esterification while enhancing cholesterol efflux. This review underscores the crucial influence of phytochemicals in modulating macrophage foam cell formation and cholesterol efflux capacity. The review summarized that a series of specific phytochemicals upregulate the expression ABCA1 and ABCG1 transporters, suppress the function of CD36, SR-A, and ACAT-1, facilitating reverse cholesterol transport (RCT) to high-density lipoprotein (HDL) and reducing intracellular cholesterol ester accumulation, ultimately conferring protective effects against atherosclerosis.