Endothelial lipase enhances low density lipoprotein binding and cell association in THP-1 macrophages

Abstract

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.

Update on the Role of Endothelial Lipase in High-Density Lipoprotein Metabolism, Reverse Cholesterol Transport, and Atherosclerosis

“…61 It is also reported that macrophages from EL −/− mice or EL-depleted macrophages have less capacity to take up LDL and oxidize LDL independently of its lypolytic function. 25, 62 These findings suggest that EL acts as a bridge between monocytes and endothelial cells, lipoproteins and macrophages, which are the initial steps of atherosclerosis. Azumi et al reported that EL is expressed in endothelial cells, smooth muscle cells, and macrophages within human atherosclerotic lesions.…”

Putative Role of Endothelial Lipase in Dialysis Patients with Hypoalbuminemia and Inflammation

“…It has been reported that atherosclerotic lesions were significantly lower in both EL and apoE knockout mice than in apoE knockout mice [27]. Furthermore, it has been shown that the EL expression is elevated in macrophages in human atherosclerotic lesions [28, 29], and that EL modulates macrophage adhesion to vessel walls [30] as well as the binding and uptake of LDL in macrophages [31]. It was also found through a clinical study that EL concentrations are associated with coronary atherosclerosis [23].…”

Molecular Biology of Atherosclerosis

“…Endothelial lipase (EL, also known as LIPG for lipase G), while usually associated with remodeling and reductions of plasma HDL can also serve as a bridge to bind LDL to cell heparan sulfated proteoglycans, promoting uptake of both native and oxLDL followed by cholesterol accumulation in macrophages (1444). EL KO in ApoE null mice reduced atherosclerosis 70% (828).…”