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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:84.)
© 2009 American Heart Association, Inc.

Cell Biology/Signaling

Endothelial Lipase Promotes Apolipoprotein AI-Mediated Cholesterol Efflux in THP-1 Macrophages

Guosong Qiu; John S. Hill

From the Atherosclerosis Specialty Laboratory, James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Providence Heart + Lung Institute, Department of Pathology and Laboratory Medicine, University of British Columbia-St. Paul’s Hospital, Vancouver, BC Canada.

Correspondence to John S. Hill, St. Paul’s Hospital, Healthy Heart Program, 1081 Burrard Street, Vancouver, BC V6Z 1Y6 Canada. E-mail jshill{at}interchange.ubc.ca

Objective— Endothelial lipase (EL) is expressed by macrophages within atherosclerotic lesions. We investigated the influence of EL expression on cholesterol efflux in macrophages.

Methods and Results— The present study used lentivirus to introduce either EL shRNA for loss-of-function studies or EL cDNA for gain-of-function studies to investigate the role of EL in apoAI-mediated cholesterol efflux. ApoAI-mediated cholesterol efflux was decreased after EL suppression, but increased with EL overexpression in free cholesterol labeled and acLDL loaded THP-1 macrophages. Similar findings were observed in THP-1 macrophages after exogenous EL addition and in transfected 293 cells. EL-related apoAI-mediated cholesterol efflux decreased after treatment with heparin or catalytic inactivation (S149A mutation or tetrahydrolipstatin) alone, and completely inhibited in combination. Furthermore, EL expression did not change ABCA1 expression, but was positively correlated with apoAI binding to macrophages and 293 cells. This effect was mitigated after heparin treatment but not influenced by catalytic inactivation via tetrahydrolipstatin or the S149A mutation. Moreover, EL expression was positively associated with lysophosphatidylcholine production and inversely with phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin levels. Lysophosphatidylcholine treatment dose-dependently stimulated apoAI-mediated cholesterol efflux in THP-1 macrophages.

Conclusion— EL appears to promote apoAI-mediated cholesterol efflux through catalytic and noncatalytic-dependent mechanisms.

Key Words: endothelial lipase • cholesterol efflux • macrophages • ATP-binding cassette transporter A1 • lentivirus