Minimally oxidized LDL inhibits macrophage selective cholesteryl ester uptake and native LDL-induced foam cell formation[S]

Scavenger receptor-mediated uptake of oxidized LDL (oxLDL) is thought to be the major mechanism of foam cell generation in atherosclerotic lesions. Recent data has indicated that native LDL is also capable of contributing to foam cell formation via low-affinity receptor-independent LDL particle pino...

Full description

Saved in:
Bibliographic Details
Published in:Journal of lipid research 2014-08, Vol.55 (8), p.1648-1656
Main Authors: Meyer, Jason M., Ji, Ailing, Cai, Lei, van der Westhuyzen, Deneys R.
Format: Article
Language:English
Subjects:
Animals
Cholesterol Esters - genetics
Cholesterol Esters - metabolism
Foam Cells - metabolism
Foam Cells - pathology
LDL oxidation
Lipoproteins, LDL - genetics
Lipoproteins, LDL - metabolism
Mice
Mice, Knockout
oxidized low density lipoprotein
Receptors, LDL - genetics
Receptors, LDL - metabolism
selective lipid uptake
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Scavenger receptor-mediated uptake of oxidized LDL (oxLDL) is thought to be the major mechanism of foam cell generation in atherosclerotic lesions. Recent data has indicated that native LDL is also capable of contributing to foam cell formation via low-affinity receptor-independent LDL particle pinocytosis and selective cholesteryl ester (CE) uptake. In the current investigation, Cu2+-induced LDL oxidation was found to inhibit macrophage selective CE uptake. Impairment of selective CE uptake was significant with LDL oxidized for as little as 30 min and correlated with oxidative fragmentation of apoB. In contrast, LDL aggregation, LDL CE oxidation, and the enhancement of scavenger receptor-mediated LDL particle uptake required at least 3 h of oxidation. Selective CE uptake did not require expression of the LDL receptor (LDL-R) and was inhibited similarly by LDL oxidation in LDL-R−/− versus WT macrophages. Inhibition of selective uptake was also observed when cells were pretreated or cotreated with minimally oxidized LDL, indicating a direct inhibitory effect of this oxLDL on macrophages. Consistent with the effect on LDL CE uptake, minimal LDL oxidation almost completely prevented LDL-induced foam cell formation. These data demonstrate a novel inhibitory effect of mildly oxidized LDL that may reduce foam cell formation in atherosclerosis.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.M044644