The susceptibility of low density lipoprotein to chemical oxidation is closely related to proneness to biological modification.
U937 is a monocytic cell line dependent on low density lipoprotein (LDL) receptor-mediated uptake of cholesterol for proliferation. However, exposure of U937 cells to LDL also results in an oxidative modification of LDL. We report here that the oxidative modification of LDL by U937 cells results in inhibition of growth and cell death. This finding suggests that analysis of U937 cell growth in presence of LDL may be used to determine the susceptibility of LDL to biological oxidative modification. There was an inverse association between the effect of LDL on U937 cell growth and the rate of degradation of U937 cell-modified LDL in mouse peritoneal macrophages (r = -0.82, p < 0.05) suggesting a coupling between proneness of LDL to develop cytotoxicity and affinity for scavenger receptors. In a group of young post-infarction patients (n = 18) the susceptibility of LDL to chemical oxidation as determined by analysis of the lag phase for formation of conjugated diens in presence of copper ions was compared with the biological modification of LDL as assessed by analysis of U937 cell growth in presence of LDL. The results demonstrated a close relation between the estimates of chemical oxidation and biological modification (r = 0.86, p < 0.005) suggesting that LDL, which is prone to become oxidised by copper also is more prone to become modified by cells in vivo.
Frostegård
J
J
Department of Medicine, King Gustaf V Research Institute, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Regnström
J
J
Tornvall
P
P
Hamsten
A
A
Nilsson
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D011973:Receptors, LDL / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D003300:Copper; D002784:Cholesterol