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 lesi ons. Acetylated low-density lipoproteins (acetyl LDL) taken up by macr ophages 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 c holesterol esterification and the metabolism of acetyl LDL. The incorp oration of C-14-oleate (complexed to albumin) into cellular cholestery l esters in tile presence of acetyl LDL (100 mu g/ml) was significantl y greater in macrophages from senescent mice (24-25 months) than in ce lls from young (3-4 months) mice (p < .001) The degradation and cellul ar association of acetyl LDL by macrophages from senescent mice were s ignificantly greater than macrophages from mature mice, (p <.001 and p < .01, respectively), whereas the binding of acetyl LDL was similar i n peritoneal macrophages from mature and senescent mice. These results suggest that the uptake and degradation of acetyl LDL, and the re-est erification by macrophages increase with advancing age and that the ab ility of macrophages to form foam cells increases with aging. The enha nced ability of senescent macrophages to form foam cells might contrib ute to the development and progression of atherosclerosis related to t he aging process.