Role of macrophages in atherosclerotic vascular lesions and xanthomas.

Intracellular accumulation of lipids occurs in macrophages and smooth muscle cells in atherosclotic vascular lesions and xanthomas associated with hypercholesterolemia. Blood monocytes are originally provided with receptors for native LDL, while macrophages are provided with another kind of receptors for denatured LDL named scavenger receptors. By treating the cells of a monocytic leukemia cell line, THP-1, by a phorbol ester, we could observe a rapid induction of the scavenger receptor with a decrease in LDL-receptor in a very short period of time (80% in 24hr). When we incubated the cells with acetylated LDL, the accumulation of cholesterol and other lipids took place and the cells were changed into foam cell. The cells can also synthesize and secrete apolipoprotein E. When we incubated the cells in the medium containing HDL or artificial lipid paricles containing apolipoprotein E, free cholesterol was released from the cell surface into the medium. The series of experiments provided us a convenient model for the study of development and regression of atherosclerosis. Probucol, a kind of antilipidemic drug provided with an activity as an antioxidant, prevented the lipid storage in macrophages. It inhibited the uptake of acetylated LDL and stimulated the release of cholesterol into the medium. Such in vitro observation explains why probucol is very effective in causing the regression of xanthomas and also in the prevention of atherosclerotic coronary heart diseases.