Metabolism of acetylated low density lipoproteins by monocyte-derived macrophages from patients with Werner's syndrome.

Abstract

Accumulation of lipid-laden foam cells of monocyte origin plays an important role in atherogenesis. Therefore, for determination of the mechanism of accelerated atherogenesis in Werner's syndrome, studies were carried out on the metabolism of acetylated low density lipoprotein (LDL) by monocyte-derived macrophages from patients with this syndrome. These macrophages showed abnormally high activities for degradation and uptake of 125I-acetylated LDL, incorporation of 14C-oleate into cellular cholesteryl ester in the presence of acetylated LDL, and accumulation of cholesteryl ester derived from internalized 3H-cholesteryl linoleate-labeled acetylated LDL. However, these macrophages showed normal binding of 125I-acetylated LDL. These results indicate that in monocyte-derived macrophages of patients with Werner's syndrome, the uptake, lysosomal hydrolysis, and re-esterification of free cholesterol are enhanced with no change in the receptor binding of acetylated LDL. As a result, these macrophages show increased accumulation of cholesteryl ester derived from acetylated LDL. This abnormal enhancement of cholesteryl ester accumulation may cause an accelerated conversion of macrophages to foam cells in Werner's syndrome.