Endothelial lipase enhances low density lipoprotein binding and cell association in THP-1 macrophages.
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.
Qiu
Guosong
G
Atherosclerosis Specialty Laboratory, Healthy Heart Program, St. Paul's Hospital, James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, Canada.
Hill
John S
JS
D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D008049:Lipase / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology