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Journal of Lipid Research, Vol 30, 1561-1568, Copyright © 1989 by Lipid Research, Inc.
I Jialal and A Chait
The rate of degradation of oxidatively modified low density lipoprotein
(Ox-LDL) by human endothelial cells was similar to that of unmodified low
density lipoprotein (LDL), and was approximately 2-fold greater than the
rate of degradation of acetylated LDL (Ac-LDL). While LDL and Ac-LDL both
stimulated cholesterol esterification in endothelial cells, Ox-LDL
inhibited cholesterol esterification by 34%, demonstrating a dissociation
between the degradation of Ox-LDL and its ability to stimulate cholesterol
esterification. Further, while LDL and Ac-LDL resulted in a 5- and 15-fold
increase in cholesteryl ester accumulation, respectively, Ox-LDL caused
only a 1.3-fold increase in cholesteryl ester mass. These differences could
be accounted for, in part, by the reduced cholesteryl ester content of
Ox-LDL. However, when endothelial cells were incubated with Ac-LDL in the
presence and absence of Ox-LDL, Ox-LDL led to a dose-dependent inhibition
of cholesterol esterification without affecting the degradation of Ac-LDL.
This inhibitory effect of Ox-LDL on cholesteryl ester synthesis was also
manifest in normal human skin fibroblasts incubated with LDL and in
LDL-receptor-negative fibroblasts incubated with unesterified cholesterol
to stimulate cholesterol esterification. Further, the lipid extract from
Ox-LDL inhibited cholesterol esterification in LDL- receptor negative
fibroblasts. These findings suggest that the inhibition of cholesterol
esterification by oxidized LDL is independent of the LDL and scavenger
receptors and may be a result of translocation of a lipid component of
oxidatively modified LDL across the cell membrane.
ARTICLES
Differences in the metabolism of oxidatively modified low density lipoprotein and acetylated low density lipoprotein by human endothelial cells: inhibition of cholesterol esterification by oxidatively modified low density lipoprotein
Department of Medicine, University of Washington, Seattle 98195.
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