Focal buildup of cholesterol in arteries is the process that produces ather
osclerotic plaques, the cause of most coronary artery disease and strokes.
Monocyte-derived macrophages are central cells that accumulate this cholest
erol in atherosclerotic lesions, a manifestation of the scavenging function
of the macrophage. Different types of cholesterol-containing lipid particl
es found in atherosclerotic lesions may enter macrophages by a variety of e
ndocytic pathways. The fate of cholesterol that enters macrophages determin
es whether macrophages help or hinder cholesterol removal from the vessel w
all. Macrophages may function to carry cholesterol out of lesions, or to pr
ocess the cholesterol for excretion in association with small protein-phosp
holipid complexes. Alternatively, macrophages that do not efficiently funct
ion to remove cholesterol from lesions may ultimately undergo cell death. S
ome cytokines, hormones, and pharmacologic agents show potential to modulat
e these processes and may be useful in directing macrophage function in ath
erosclerotic lesions towards beneficial rather than harmful effects.