Altered hepatic catabolism of low-density lipoprotein subjected to lipid peroxidation in vitro

W. L. Stone, M. Heimberg, R. L. Scott, I. LeClair, H. G. Wilcox

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Recent evidence suggests that oxidatively modified forms of low density lipoprotein (LDL) may be particularly atherogenic. In this investigation, the catabolism of human LDL modified by lipid peroxidation in vitro was studied with a recirculating rat liver perfusion system. A dual-labelling technique was used that permitted native LDL and modified LDL to be studied simultaneously in the liver perfusion system. Native human LDL was found to have a fractional catabolic rate (FCR) of 1.00±0.21%/h, in agreement with other investigators. Subjecting LDL to oxidation for 12h in the presence of 30 μM FeEDTA did not significantly affect its FCR. LDL treated with a superoxide-generating system (xanthine oxidase, hypoxanthine O2) in the presence of 30 μM FeEDTA did, however, show a significant increase in FCR (3.23±0.19%/h). The hepatic uptakes of native LDL and LDL oxidized with FeEDTA + O2 were similar, but both were significantly lower than the hepatic uptake of LDL treated with the superoxide-radical-generating system. The proteolysis of LDL with pancreatin did not influence either its susceptibility to oxidation or its FCR. LDL oxidation resulted in the preferential loss of α-tocopherol rather than γ-tocopherol. These data indicate that the rat liver effectively catabolizes LDL oxidatively modified by treatment with the superoxide-generating system. Furthermore, our results suggest that only very low plasma levels of highly oxidized LDL could be found under conditions in vivo. The liver may therefore play a major role in protecting the arterial vasculature from highly atherogenic forms of LDL.

Original languageEnglish (US)
Pages (from-to)573-579
Number of pages7
JournalBiochemical Journal
Issue number3
StatePublished - 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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