Oxidative modification of beta-very low density lipoprotein. Potential role in monocyte recruitment and foam cell formation.
Oxidative modification of low density lipoprotein (LDL) generates a form that is degraded much more rapidly by macrophages and may thus be more atherogenic than unoxidized LDL. Recently, we provided evidence that oxidative modification of LDL may play a significant role in the generation of fatty streaks in the LDL receptor-deficient rabbit. The major lipoprotein in cholesterol-fed animals is the beta-very low density lipoprotein (beta-VLDL). Since beta-VLDL is avidly taken up by macrophages, it could lead to foam cell formation without the need for oxidative modification or modification of other kinds. However, the present studies show that beta-VLDL can be oxidized by incubation with endothelial cells or with copper ions. Oxidized beta-VLDL was degraded by macrophages at about twice the rate of unoxidized beta-VLDL, and it stimulated cholesterol esterification twice as much as unoxidized beta-VLDL. The degradation of oxidized beta-VLDL was inhibited either by oxidized beta-VLDL itself or by oxidized LDL, but not by unoxidized beta-VLDL. beta-VLDL was chemotactic for human monocytes and contained significant amounts of lysophosphatidylcholine, previously shown to be a chemotactic agent. In summary, oxidized LDL is degraded by macrophages proportionately more than oxidized beta-VLDL as compared to the unmodified lipoproteins. However, the twofold increase may, nevertheless, be significant in the atherogenicity of beta-VLDL.
Parthasarathy
S
S
Department of Medicine, University of California, San Diego, La Jolla 92093.
Quinn
M T
MT
Schwenke
D C
DC
Carew
T E
TE
Steinberg
D
D
D000818:Animals; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005487:Foam Cells / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008079:Lipoproteins, VLDL / Q000032:analysis / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000032:analysis; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D010084:Oxidation-Reduction; D011817:Rabbits
D008079:Lipoproteins, VLDL; D008244:Lysophosphatidylcholines