Chemically or biologically modified low-density lipoproteins (LDL) but not native unmodified LDL lead to foam cell formation in monocyte-derived macrophages. Since the magnitude of postprandial lipemia after a challenge test seems to be associated with coronary artery disease, we tested the hypothesis that in the course of postprandial lipemia, LDL appear in plasma that are capable of leading to foam cell formation even without prior modification. We incubated the macrophage-like cell line P388 with unmodified postabsorptive and postprandial LDL from 17 healthy donors and measured the cellular cholesterol and triglyceride contents and amounts of exogenous [C-14]oleic acid incorporated into the cholesteryl ester fraction. Postprandial LDL induced a significantly more pronounced cholesteryl ester accumulation than did postabsorptive LDL (477+/-286% versus 212+/-173%, respectively; P<.003). The increase in cellular total cholesterol was significantly higher as a result of cell incubation with postprandial LDL (107+/-61%) than with postabsorptive LDL (54+/-40%, P<.003), whereas no increase in triglyceride content was observed (P<.589) in either case. After CuSO4 incubation and incubation with P388 cells, postprandial LDL revealed more thiobarbituric acid-reacting substances than did postabsorptive LDL (55+/-10 versus 28+/-9 nmol/mg protein, P<.018; 28+/-4 versus 20+/-3 nmol/mg protein). The increase in Cellular cholesteryl ester synthesis caused by postprandial LDL was reduced by more than 50% when lipoproteins and cells were incubated in the presence of ascorbic acid (P<.007). In competition studies, cellular binding and degradation of I-125-labeled postprandial LDL were reduced 30% by cold acetyl-LDL, and coincubation of postprandial LDL with acetyl-LDL resulted in no further increase in cellular cholesteryl ester accumulation. Our results are consistent with the view that both lipoproteins may share the same cellular uptake mechanism and that this mechanism might be the scavenger receptor. From our results the reason for the increased atherogenicity of postprandial LDL appears to be a greater susceptibility to chemical modification such as oxidation during incubation with cells in culture.
