Qiu_2007_Cardiovasc.Res_76_528

OBJECTIVE: Endothelial lipase (EL) is expressed in macrophages in human atherosclerotic lesions. However, its specific metabolic role in human macrophages has not been fully explored.
METHODS: The present study used lentivirus containing either shRNA or cDNA for EL to decrease or increase EL expression, respectively in THP-1 macrophages to investigate the consequence on LDL binding and cell association.
RESULTS: EL suppression significantly decreased the binding and cell association of native LDL (52% and 33%) and mildly oxLDL (43% and 36%) as well as extensively oxLDL binding (36%) in THP-1 macrophages. EL overexpression markedly increased the binding and cell association of native LDL (3.1- and 2.2-fold), mildly oxLDL (1.9- and 1.4-fold), and extensively oxLDL (1.5- and 1.5-fold). An inactive mutant EL compromised EL-mediated cell association of native and mildly oxLDL but not extensively oxLDL. Heparinase treatment almost completely eliminated EL-mediated native and oxLDL binding and cell association in THP-1 macrophages. LDL receptor blocking by antibodies decreased EL-mediated native LDL binding and cell association by 24% and 54%, respectively. Neither receptor associated protein or CD36 antibody treatment led to changes in EL-mediated lipoprotein binding and cell association. Furthermore, wild-type and the catalytically inactive mutant EL increased lipid accumulation in THP-1 macrophages.
CONCLUSIONS: EL expression promotes the binding and uptake of native and oxidized LDL in THP-1 macrophages in a heparan sulfate proteoglycan-dependent manner, and the LDL receptor was partly responsible for the EL-enhanced uptake of native LDL.