Ms. Nenseter et al., EFFECT OF CHOLESTEROL FEEDING ON THE SUSCEPTIBILITY OF LIPOPROTEINS TO OXIDATIVE MODIFICATION, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1213(2), 1994, pp. 207-214
In previous studies we have shown that the liver endothelial and Kupff
er cells in hypercholesterolemic rabbits are very active in endocytosi
s of low-density lipoprotein (LDL) and beta-very-low-density lipoprote
in (beta-VLDL) (Nenseter et al. (1997,) J. Lipid Res. 33, 867-877; Gud
mundsen et al. (1993) J. Lipid Res, 34, 589-600). These data raised th
e question whether subfractions of LDL and beta-VLDL were modified in
vivo to forms recognized by the scavenger/oxidized LDL receptors of th
e non-parenchymal liver cells. The purpose of the present study was to
address this question by assessing the effect of cholesterol feeding
on the susceptibility of the lipoproteins to oxidative modification in
vitro. In addition, the effect of HDL on the lipid peroxidation of LD
L was evaluated. LDL and beta-VLDL were isolated from rabbits given a
diet supplemented with cholesterol (2% w/w) for 3 weeks. The extent of
Cu2+-catalyzed oxidation of the lipoproteins was compared with that o
f LDL from control-fed rabbits. Extent of oxidation assessed by format
ion of conjugated dienes, lipid peroxides, thiobarbituric acid-reactiv
e substances, relative electrophoretic mobility and uptake of lipoprot
eins by J774 macrophages suggested that LDL and beta-VLDL from the hyp
ercholesterolemic rabbits were more susceptible to oxidation than LDL
from normolipidemic rabbits. HDL protected LDL and beta-VLDL from lipi
d peroxidation in vitro. Taken together, the increased susceptibility
of LDL and beta-VLDL to oxidative modification in vitro, combined with
the low levels of alpha-tocopherol, and the reduced ratio of HDL to L
DL cholesterol observed in the hypercholesterolemic rabbits, and the p
rotective effect of HDL on the lipid peroxidation of LDL, support the
probability that oxidative modification of LDL and beta-VLDL occur in
vivo in the hypercholesterolemic rabbits.