Apolipoprotein E and lipoprotein lipase reduce macrophage degradation of oxidized very-low-density lipoprotein (VLDL), but increase cellular degradation of native VLDL.
Oxidized low-density lipoprotein (Ox-LDL) has been shown to be taken up by the macrophage-scavenger receptor at an enhanced rate in comparison to native LDL, with consequent cellular cholesterol accumulation. In the present study, we analyzed macrophage interaction with very-low-density lipoprotein (VLDL) from normolipidemic subjects (N-VLDL) that was oxidized in the presence of 10 mumol/L copper ions. Oxidized VLDL (Ox-VLDL) contained increased conjugated dienes and malondialdehyde (MDA) equivalents and showed increased electrophoretic mobility. Gradual fragmentation of VLDL apolipoproteins (apo) was noted, with apo B-100 being the first to be fragmented, followed by apo E and apo C. Degradation of Ox-VLDL by mouse peritoneal macrophages (MPM) was increased almost twofold in comparison to N-VLDL. Upon incubation of VLDL with lipoprotein lipase (LPL), the LPL-treated lipoprotein demonstrated up to 50% increased degradation by macrophages in comparison to control N-VLDL. However, the degradation of LPL-treated Ox-VLDL was decreased by up to 20% in comparison to control Ox-VLDL. Similarly, the addition of apo E to VLDL enhanced its cellular degradation by 56%, whereas a 20% reduction in the degradation of apo E-treated Ox-VLDL was demonstrated in comparison to nontreated Ox-VLDL. These results showed that LPL and apo E, two important regulatory substances in cellular metabolism of plasma lipoproteins, increased macrophage degradation of native VLDL, but reduced the degradation of Ox-VLDL. These inhibitory effects on macrophage uptake of Ox-VLDL suggest that apo E and LPL may possess antiatherogenic potential.
Keidar
S
S
Lipid Research Unit, Rambam Medical Center, Haifa, Israel.
Kaplan
M
M
Rosenblat
M
M
Brook
G J
GJ
Aviram
M
M
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003864:Depression, Chemical; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D010529:Peritoneal Cavity / Q000166:cytology; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D001057:Apolipoproteins E; D008079:Lipoproteins, VLDL; D008071:Lipoprotein Lipase