The macrophage in atherosclerosis: modulation of cell function by sterols

Lipid-laden macrophage foam cells are an early and persistent component of atherosclerotic lesions. As such they are likely to play a key role in disease progression, both as scavengers of lipid and as inflammatory mediators. The sterol content of macrophage foam cells is largely native cholesterol together with a small but significant proportion of oxidized cholesterol (oxysterols). Few in vitro investigations of the influence of sterol accumulation on macrophage function have used cells that contain physiologically or even pathologically representative amounts of cholesterol or, more particularly, oxysterols. However, recent studies, using macrophages with a sterol content much closer to that of authentic foam cells, show that the presence of oxysterols causes an impairment in macrophage cholesterol export, suggesting a key role for oxysterols in the maintenance of the foam cell phenotype. The implications of physiologically relevant levels of oxysterols on a wider range of macrophage function remain to be investigated.