Wl. Stone et al., ALTERED HEPATIC CATABOLISM OF LOW-DENSITY-LIPOPROTEIN SUBJECTED TO LIPID-PEROXIDATION IN-VITRO, Biochemical journal, 297, 1994, pp. 573-579
Recent evidence suggests that oxidatively modified forms of low-densit
y lipoprotein (LDL) may be particularly atherogenic. In this investiga
tion, the catabolism of human LDL modified by lipid peroxidation in vi
tro was studied with a recirculating rat liver perfusion system. A dua
l-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 o
xidation for 12 h in the presence of 30 mu M FeEDTA. did not significa
ntly affect its FCR. LDL treated with a superoxide-generating system (
xanthine oxidase, hypoxanthine, O-2) in the presence of 30 mu M FeEDTA
did, however, show a significant increase in FCR (3.23+/-0.19%/h). Th
e hepatic uptakes of native LDL and LDL oxidized with FeEDTA + O-2 wer
e similar, but both were significantly lower than the hepatic uptake o
f LDL treated with the superoxide-radical-generating system. The prote
olysis of LDL with pancreatin did not influence either its susceptibil
ity to oxidation or its FCR. LDL oxidation resulted in the preferentia
l loss of alpha-tocopherol rather than gamma-tocopherol. These data in
dicate that the rat liver effectively catabolizes LDL oxidatively modi
fied by treatment with the superoxide-generating system. Furthermore,
our results suggest that only very low plasma levels of highly oxidize
d 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.