Oxidation of low density lipoproteins greatly enhances their association with lipoprotein lipase anchored to endothelial cell matrix.
Native and oxidized low density lipoprotein retention within arterial wall endothelial cell matrix ( ECM) is an early event in the pathogenesis of atherosclerosis. Previously we showed lipoprotein lipase (LPL) addition to ECM enhanced the retention of apoB-containing lipoproteins. In the present studies we examined whether the oxidation of low density lipoprotein (LDL) increases its retention by LPL-containing ECM. Except where noted, 125I-labeled moderately oxidized LDL (ModOxLDL) was prepared by long term storage of 125I-LDL. Without LPL, 125I-ModOxLDL matrix binding was low and nonsaturable. LPL preanchored to ECM resulted in 125I-ModOxLDL binding that was saturable and 20-fold greater than in the absence of LPL, with an association constant equal to 2.6 nM. Copper-oxidized LDL (Cu-OxLDL) was able to compete with 125I-ModOxLDL, whereas a 60-fold native LDL excess had no effect. Reconstituted apolipoprotein B from Cu-OxLDL also reduced 125I-ModOxLDL to LPL, whereas liposomes derived from the lipid extract of Cu-OxLDL had no effect on binding. These data suggest that the increased binding of oxidized LDL to LPL- ECM may be due to the exposure of novel apoB binding sites and not an oxidized lipid moiety. 125I-ModOxLDL binding was also not affected by either preincubation with a 300-fold molar excess of apoE-poor HDL or an 340-fold molar excess of Cu-Ox-HDL. In contrast, a 4-fold apoE-rich HDL excess (based on protein) totally inhibited 125I-ModOxLDL matrix retention. Positively charged peptides of polyarginine mimicked the effect of apoE-rich HDL in reducing the 125I-ModOxLDL retention; however, polylysine had no effect. We postulate that the oxidation of LDL may be a mechanism that enhances LDL retention by the ECM- bound LPL and that the protective effects of apoE-containing HDL may in part be due to its ability to block the retention of oxidized LDL in vivo.[1]References
- Oxidation of low density lipoproteins greatly enhances their association with lipoprotein lipase anchored to endothelial cell matrix. Auerbach, B.J., Bisgaier, C.L., Wölle, J., Saxena, U. J. Biol. Chem. (1996) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg