Endogenous apolipoprotein E modulates cholesterol efflux and cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 and lipid-free apolipoproteins in mouse peritoneal macrophages

2000 ◽  
Vol 78 (4) ◽  
pp. 217-227 ◽  
Author(s):  
Claus Langer ◽  
Yadong Huang ◽  
Paul Cullen ◽  
Bernd Wiesenhütter ◽  
Robert W. Mahley ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Apolipoprotein E ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Peritoneal Macrophages ◽  
Ester Hydrolysis ◽  
High Density ◽  
Mouse Peritoneal Macrophages

scholarly journals ADAM17 Boosts Cholesterol Efflux and Downstream Effects of High-Density Lipoprotein on Inflammatory Pathways in Macrophages

2021 ◽  
Author(s):  
Vishal Kothari ◽  
Jingjing Tang ◽  
Yi He ◽  
Farah Kramer ◽  
Jenny E. Kanter ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Myeloid Cell ◽  
Peritoneal Macrophages ◽  
High Density ◽  
Cholesterol Depletion ◽  
Proinflammatory Responses ◽  
Anti Inflammatory

Objective: HDL (high-density lipoprotein) can exert both anti-inflammatory and proinflammatory effects in macrophages due to its ability to induce cholesterol depletion. Because cholesterol depletion also increases sheddase activity of the membrane protease ADAM17 (ADAM metallopeptidase domain 17) in other cells, we examined if ADAM17 plays a role in HDL’s effects on inflammatory processes in macrophages in vitro and in vivo. Approach and Results: Sorted peritoneal macrophages from human APOA1 (apolipoprotein A1) transgenic LDL (low-density lipoprotein) receptor-deficient ( APOA1 Tg ; Ldlr −/− ) mice with and without myeloid cell-targeted ADAM17-deficiency were studied in parallel with wildtype and ADAM17-deficient bone marrow-derived macrophages stimulated with HDL in vitro. HDL increased ADAM17 expression and activity in macrophages. Furthermore, ADAM17-deficient macrophages exhibited reduced expression of ABCA1 (ATP-binding cassette A1) and reduced cholesterol efflux and were cholesterol loaded. This was caused by the absence of shedding of TNFα, a major ADAM17 substrate. Sorted thioglycollate-elicited peritoneal macrophages freshly isolated from APOA1 Tg ; Ldlr −/− mice, which have higher HDL levels than Ldlr −/− controls, showed reduced expression of interferon-inducible genes in response to lipopolysaccharide or interferon-β, but exacerbated proinflammatory responses to lipopolysaccharide for Tnfa , Cxcl1 , Ccl2 , and Il1b , phenocopying cells stimulated with HDL in vitro. These effects were all prevented in ADAM17-deficient macrophages and associated with lower concentrations of large HDL particles in APOA1 Tg ; Ldlr −/− mice with myeloid cell-targeted ADAM17-deficiency. Conclusions: The increased cholesterol loading of ADAM17-deficient macrophages prevents both anti-inflammatory and proinflammatory responses of HDL. Our findings demonstrate a novel role for ADAM17 in maintaining cholesterol efflux in macrophages, thereby regulating the immune functions of these cells.

Characterization of the cholesterol efflux of apolipoprotein E-containing high-density lipoprotein in THP-1 cells

2019 ◽  
Vol 400 (2) ◽  
pp. 209-218 ◽  
Author(s):  
Yuna Horiuchi ◽  
Ryunosuke Ohkawa ◽  
Shao-Jui Lai ◽  
Azusa Yamazaki ◽  
Hayato Ikoma ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Apolipoprotein E ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Response To Treatment ◽  
Atp Binding Cassette Transporter ◽  
A Minor

Abstract High-density lipoprotein (HDL), also known as antiatherogenic lipoprotein, consists of heterogeneous particles in terms of size, density and composition, suggesting differences among HDL subclasses in characteristics and functions. We investigated the role of apolipoprotein E (apoE)-containing HDL, a minor HDL subclass, in the cholesterol efflux capacity (CEC) of HDL, which is its predominant atheroprotective function. The CEC of apoE-containing HDL was similar to that of apoE-deficient HDL, but the former exhibited a greater rate increase (1.48-fold) compared to that of the latter (1.10-fold) by the stimulation of THP-1 macrophages with the Liver X Receptor (LXR) agonist. No difference in CEC was observed without the LXR agonist between apoA-I, the main apolipoprotein in HDL, and apoE, whereas the increase in CEC in response to treatment with the LXR agonist was greater for apoA-I (4.25-fold) than for apoE (2.22-fold). Furthermore, the increase in the CEC of apoE-containing HDL induced by the LXR agonist was significantly reduced by treatment with glyburide, an inhibitor of ATP-binding cassette transporter A1 (ABCA1). These results suggest that apoE-containing HDL, unlike apoE-deficient HDL, is involved in cholesterol efflux via ABCA1.

Cholesterol efflux from normal and Tangier disease fibroblasts into normal, high-density lipoprotein-deficient, and apolipoprotein E-deficient plasmas

Metabolism ◽  
2000 ◽  
Vol 49 (6) ◽  
pp. 770-777 ◽  
Author(s):  
S. Schuler-Lüttmann ◽  
Y. Zhu ◽  
M. Hoffmann ◽  
W. März ◽  
G. Feussner ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Apolipoprotein E ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Tangier Disease
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