AGE-RELATED-CHANGES IN THE METABOLISM OF ACETYLATED LOW-DENSITY LIPOPROTEINS BY PERITONEAL-MACROPHAGES FROM C57BL/6CRSCL MICE

Macrophages are major precursors of foam cells in atherosclerotic lesions. Acetylated low-density lipoproteins (acetyl LDL) taken up by macrophages through scavenger receptors are degraded by lysosomes and the released cholesterol is re-esterified, leading to foam cell formation. The ability of resident peritoneal macrophages from C57BL/6CrScl mice to form foam cells in relation to the donor age was assessed by the cholesterol esterification and the metabolism of acetyl LDL. The incorporation of C-14-oleate (complexed to albumin) into cellular cholesteryl esters in the presence of acetyl LDL (100 mu g/ml) was significantly greater in macrophages from senescent mice (24-25 months) than in cells from young (3-4 months) mice (p < .001) The degradation and cellular association of acetyl LDL by macrophages from senescent mice were significantly greater than macrophages from mature mice, (p <.001 and p < .01, respectively), whereas the binding of acetyl LDL was similar in peritoneal macrophages from mature and senescent mice. These results suggest that the uptake and degradation of acetyl LDL, and the re-esterification by macrophages increase with advancing age and that the ability of macrophages to form foam cells increases with aging. The enhanced ability of senescent macrophages to form foam cells might contribute to the development and progression of atherosclerosis related to the aging process.