ALTERED HEPATIC CATABOLISM OF LOW-DENSITY-LIPOPROTEIN SUBJECTED TO LIPID-PEROXIDATION IN-VITRO

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.