| Title: |
Implication of lipoprotein associated phospholipase A2activity in oxLDL uptake by macrophages |
| Authors: |
Markakis, Konstantinos P., Koropouli, Maria K., Grammenou-Savvoglou, Stavroula, van Winden, Ewoud C., Dimitriou, Andromaxi A., Demopoulos, Constantinos A., Tselepis, Alexandros D., Kotsifaki, Eleni E. |
| Source: |
Journal of Lipid Research; August 2010, Vol. 51 Issue: 8 p2191-2201, 11p |
| Abstract: |
Recognition and uptake of oxidized LDL (oxLDL) by scavenger receptors of macrophages and foam cell formation are mediated by the oxidatively modified apolipoprotein B (ApoB) and lipid moiety of oxLDL. A great amount of oxidized phosphatidylcholine (oxPC) of oxLDL is hydrolyzed at the sn-2 position by lipoprotein associated phospholipase A2(Lp-PLA2) to lysophosphatidylcholine and small oxidation products. This study examines the involvement of Lp-PLA2in the uptake of oxLDL by mouse peritoneal macrophages. LDL with intact Lp-PLA2activity [LDL (+)] and LDL with completely inhibited Lp-PLA2activity [LDL (-)] were subjected to oxidation with 5 µM CuSO4for 6 h [moderately oxLDL (MoxLDL)], or 24 h [heavily oxLDL (HoxLDL)] and peritoneal macrophages were incubated with these preparations. The uptake of MoxLDL(-) was about 30% increased compared with that of MoxLDL(+), and HoxLDL(-) uptake was about 20% increased compared with that of HoxLDL(+). Inhibition of Lp-PLA2activity had no effect on the uptake of ApoB-liposomes conjugates with ApoB isolated from MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+). Liposomes prepared from the lipid extract of MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+) exhibited a similar pattern to that observed in the uptake of the corresponding intact lipoproteins. This study suggests that the progressive inactivation of Lp-PLA2during LDL oxidation leads to an increased uptake of oxLDL by macrophages, which could be primarily attributed to the increased uptake of the oxidized phospholipids enriched lipid moiety of oxLDL. |
| Database: |
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