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 pathogenes is of atherosclerosis. Previously we showed lipoprotein lipase (LPL) a ddition to ECM enhanced the retention of apoB-containing lipoproteins. In the present studies we examined whether the oxidation of low densi ty lipoprotein (LDL) increases its retention by LPL-containing ECM, Ex cept where noted, I-125-labeled moderately oxidized LDL (ModOx-LDL) wa s prepared by long term storage of I-125-LDL. Without LPL, I-125-ModOx LDL matrix binding was low and nonsaturable, LPL preanchored to ECM re sulted in I-125-ModOxLDL binding that was saturable and 20-fold greate r than in the absence of LPL, with an association constant equal to 2. 6 nM, Copper-oxidized LDL (Cu-Ox-LDL) was able to compete with I-125-M odOxLDL, whereas a 60-fold native LDL excess had no effect, Reconstitu ted apolipoprotein B from Cu-OxLDL also reduced I-125-ModOxLDL to LPL, whereas liposomes derived from the lipid extract of Cu-OxLDL had no e ffect on binding, These data suggest that the increased binding of oxi dized LDL to LPL ECM may be due to the exposure of novel apoB binding sites and not an oxidized lipid moiety, I-125-ModOxLDL binding was als o 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 I-fold apoE-rich HDL excess (based on protein) totally inhibited I-1 25-ModOxLDL matrix retention, Positively charged peptides of polyargin ine mimicked the effect of apoE-rich HDL in reducing the I-125-ModOxLD L 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 LPE and that the protective effects of apoE-containing HDL may in part be due to its ability to block the retention of oxidized L DL in vivo.