Online citations, reference lists, and bibliographies.
← Back to Search

Inhibition Of LPL Expression In Human Monocyte-derived Macrophages Is Dependent On LDL Oxidation State: A Key Role For Lysophosphatidylcholine.

D. Stengel, M. Antonucci, W. Gaoua, C. Dachet, P. Lesnik, D. Hourton, E. Ninio, M. Chapman, S. Griglio
Published 1998 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
The regulation of macrophage lipoprotein lipase (LPL) secretion and mRNA expression by atherogenic lipoproteins is of critical relevance to foam cell formation. LPL is present in arterial lesions and constitutes a bridging ligand between lipoproteins, proteoglycans, and cell receptors, thus favoring macrophage lipoprotein uptake and lipid accumulation. We investigated the effects of native and of oxidized lipoproteins on the expression of LPL in an in vitro human monocyte-macrophage system. Exposure of mature macrophages (day 12) to highly copper-oxidized human low density lipoprotein (LDL) (100 microg protein per milliliter) led to marked reduction in the expression of LPL activity (-62%, P<0.01) and mRNA level (-47%, P<0.05); native LDL, acetylated LDL, and LDL oxidized for <6 hours were without effect. The reduction in LPL activity became significant at a threshold of 6 hours of LDL oxidation (-31%, P<0.05). Among the biologically active sterols formed during LDL oxidation, only 7beta-hydroxycholesterol (5 microg/mL) induced a minor reduction in macrophage LPL activity, whereas 25-hydroxycholesterol was without effect. By contrast, lysophosphatidylcholine, whose LDL content increased in parallel with the degree of oxidation, induced significant reductions in LPL activity and mRNA levels at concentrations of 2 to 20 micromol/L (-34% to -53%, P<0.01). Our results demonstrate that highly oxidized LDL (>6-hour oxidation) exerts negative feedback on LPL secretion in human monocytes-macrophages via a reduction in mRNA levels. By contrast, native LDL and mildly oxidized LDL (<6-hour oxidation) did not exert a feedback effect on LPL expression. We speculate that the content of lysophosphatidylcholine and, to a lesser degree, of 7beta-hydroxycholesterol in oxidized LDLs is responsible for the downregulation of LPL activity and mRNA abundance in human monocyte-derived macrophages and may therefore modulate LPL-mediated pathways of lipoprotein uptake during conversion of macrophages to foam cells.
This paper references
10.1172/JCI114562
Minimally modified low density lipoprotein stimulates monocyte endothelial interactions.
J. Berliner (1990)
10.1161/01.ATV.15.10.1591
Transcriptional activation of the macrophage-colony stimulating factor gene by minimally modified LDL. Involvement of nuclear factor-kappa B.
T. Rajavashisth (1995)
Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis.
I. Goldberg (1996)
Oxidized LDL binds to CD36 on human monocyte-derived macrophages and transfected cell lines.Arterioscler
AC Nicholson (1994)
10.1002/PATH.1711710413
Cytotoxicity of oxidized low‐density lipoprotein to mouse peritoneal macrophages: An ultrastructural study
V. C. Reid (1993)
A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent.
M. el-Saadani (1989)
10.1016/0891-5849(92)90181-F
The role of lipid peroxidation and antioxidants in oxidative modification of LDL.
H. Esterbauer (1992)
10.1074/JBC.270.26.15747
Enhancement of the Binding of Triglyceride-rich Lipoproteins to the Very Low Density Lipoprotein Receptor by Apolipoprotein E and Lipoprotein Lipase (*)
S. Takahashi (1995)
A macrophage Fc receptor for IgG is also a receptor for oxidized low density lipoprotein.
L. Stanton (1992)
10.1042/BJ3140563
Lipoprotein lipase stimulates the binding and uptake of moderately oxidized low-density lipoprotein by J774 macrophages.
W. L. Hendriks (1996)
Further resolution of the low density lipoprotein spectrum in normal human plasma: physicochemical characteristics of discrete subspecies separated by density gradient ultracentrifugation.
M. Chapman (1988)
10.1073/PNAS.73.9.3178
Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts.
S. K. Basu (1976)
10.1161/01.ATV.12.5.608
Scavenger receptor-independent stimulation of cholesterol esterification in macrophages by low density lipoprotein extracted from human aortic intima.
U. Steinbrecher (1992)
10.1074/jbc.271.44.27346
The Scavenger Receptor Serves as a Route for Internalization of Lysophosphatidylcholine in Oxidized Low Density Lipoprotein-induced Macrophage Proliferation*
M. Sakai (1996)
10.1097/00041433-199510000-00009
Triglyceride lpases and atherosclerosis
G. Olivecrona (1995)
10.1172/JCI114271
Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man.
S. Ylä-Herttuala (1989)
10.1073/PNAS.88.22.10143
Macrophages and smooth muscle cells express lipoprotein lipase in human and rabbit atherosclerotic lesions.
S. Ylä-Herttuala (1991)
10.1172/JCI117490
Inactivation of lysosomal proteases by oxidized low density lipoprotein is partially responsible for its poor degradation by mouse peritoneal macrophages.
G. Hoppe (1994)
Simple liquid-liquid partition system for isolation of labeled oleic acid from mixtures with glycerides.
P. Belfrage (1969)
10.1161/01.ATV.17.1.141
Oxidized LDL stimulates mitogen-activated protein kinases in smooth muscle cells and macrophages.
M. Kusuhara (1997)
10.1161/01.ATV.10.2.246
Expression of elastase activity by human monocyte-macrophages is modulated by cellular cholesterol content, inflammatory mediators, and phorbol myristate acetate.
M. Rouis (1990)
10.1073/PNAS.87.13.5134
Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells.
S. D. Cushing (1990)
10.1172/JCI115747
Lipoprotein lipase is synthesized by macrophage-derived foam cells in human coronary atherosclerotic plaques.
K. O'brien (1992)
10.1161/01.CIR.94.6.1216
Oxidation-specific epitopes in human coronary atherosclerosis are not limited to oxidized low-density lipoprotein.
K. O'brien (1996)
Sensitive detection of oxidatively modified low density lipoprotein using a monoclonal antibody.
H. Itabe (1996)
Electrophoretic separation of plasma lipoproteins in agarose gel.
R. P. Noble (1968)
10.1016/0005-2760(66)90056-7
Hydrolysis of cholesteryl linoleate by a high-speed supernatant preparation of rat and monkey aorta.
C. F. Howard (1966)
10.1161/01.ATV.14.6.1000
Induction of LDL receptor-related protein during the differentiation of monocyte-macrophages. Possible involvement in the atherosclerotic process.
Y. Watanabe (1994)
10.1097/00041433-199410000-00010
The arterial wall and the atherosclerotic lesion
J. Guyton (1994)
10.1016/S0021-9150(97)00124-X
Effect of the oxidation state of LDL on the modulation of arterial vasomotor response in vitro.
N. Mougenot (1997)
Lysophosphatidylcholine concentrations and metabolism in aortic intima plus inner media: effect of nutritionally induced atherosclerosis.
O. Portman (1969)
10.1172/JCI116764
Expression of lipoprotein lipase mRNA and secretion in macrophages isolated from human atherosclerotic aorta.
L. Mattsson (1993)
10.1161/01.ATV.15.4.534
Selective retention of VLDL, IDL, and LDL in the arterial intima of genetically hyperlipidemic rabbits in vivo. Molecular size as a determinant of fractional loss from the intima-inner media.
B. G. Nordestgaard (1995)
Ultrastructure of the intima in WHHL and cholesterol-fed rabbit aortas prepared by ultra-rapid freezing and freeze-etching.
J. Frank (1989)
10.1073/PNAS.91.24.11452
7 beta-hydroperoxycholest-5-en-3 beta-ol, a component of human atherosclerotic lesions, is the primary cytotoxin of oxidized human low density lipoprotein.
G. Chisolm (1994)
10.1073/PNAS.88.19.8342
Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein.
U. Beisiegel (1991)
10.1016/0021-9150(95)05594-M
Toxicity of oxysterols to human monocyte-macrophages.
K. Clare (1995)
CD36 is a receptor for oxidized low density lipoprotein.
G. Endemann (1993)
Cellular binding site and membrane binding proteins for triglyceride-rich lipoproteins in human monocyte-macrophages and THP-1 monocytic cells.
S. Gianturco (1994)
10.1074/JBC.271.43.27090
The Bioactive Phospholipid, Lysophosphatidylcholine, Induces Cellular Effects via G-Protein-dependent Activation of Adenylyl Cyclase*
Y. Yuan (1996)
10.1056/NEJM198904063201407
Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity.
D. Steinberg (1989)
10.1016/S0076-6879(78)52032-6
Microsomal lipid peroxidation.
J. A. Buege (1978)
10.1016/0009-3084(95)02489-6
Time course of oxysterol formation during in vitro oxidation of low density lipoprotein.
S. Dželetović (1995)
10.1161/01.ATV.17.5.954
Expression of the PAF receptor in human monocyte-derived macrophages is downregulated by oxidized LDL: relevance to the inflammatory phase of atherogenesis.
D. Stengel (1997)
10.1016/0014-5793(93)81655-J
Potentiation of diacylglycerol‐induced activation of protein kinase C by lysophospholipids
Y. Sasaki (1993)
Ultrastructure of the intima in WHHL and cholesterol-fed rabbit aortas prepared by ultra-rapid freezing and freezeetching.J Lipid Res. 1989;30:967–978
JS Frank (1989)
10.1161/01.ATV.14.4.622
Liposome-like particles isolated from human atherosclerotic plaques are structurally and compositionally similar to surface remnants of triglyceride-rich lipoproteins.
B. Chung (1994)
10.1074/jbc.271.3.1329
Oxidation of Low Density Lipoproteins Greatly Enhances Their Association with Lipoprotein Lipase Anchored to Endothelial Cell Matrix (*)
B. Auerbach (1996)
10.1161/01.ATV.15.2.269
Oxidized LDL binds to CD36 on human monocyte-derived macrophages and transfected cell lines. Evidence implicating the lipid moiety of the lipoprotein as the binding site.
A. C. Nicholson (1995)
10.1016/S0006-291X(05)81008-3
Phospholipase A2-modified LDL is taken up at enhanced rate by macrophages.
M. Aviram (1992)
10.1172/JCI118436
Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages.
L. Hultén (1996)
10.1161/01.ATV.14.11.1767
Triglyceride-rich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque.
J. Rapp (1994)
10.1161/01.ATV.15.2.276
Apolipoprotein A-I-mediated efflux of sterols from oxidized LDL-loaded macrophages.
L. Kritharides (1995)
10.1016/0005-2760(66)90055-5
Squalene, 26-hydroxycholesterol and 7-ketocholesterol in human atheromatous plaques.
C. J. Brooks (1966)
10.1146/ANNUREV.PH.57.030195.004043
Cell biology of atherosclerosis.
R. Ross (1995)
Protein measurement with the Folin phenol reagent.
O. H. Lowry (1951)
A simple method for the isolation and purification of total lipides from animal tissues.
J. Folch (1957)
10.1161/01.ATV.16.2.194
Active oxygen species and lysophosphatidylcholine are involved in oxidized low density lipoprotein activation of smooth muscle cell DNA synthesis.
A. Stiko (1996)
Rapid, simple and specific assays for lipoprotein lipase and hepatic lipase
P Nilsson-Ehle (1977)
Lipoprotein lipase and sphingomyelinase synergistically enhance the association of atherogenic lipoproteins with smooth muscle cells and extracellular matrix. A possible mechanism for low density lipoprotein and lipoprotein(a) retention and macrophage foam cell formation.
I. Tabas (1993)
Lipoprotein lipase (LpL) affects low density lipoprotein (LDL) flux through vascular tissue: evidence that LpL increases LDL accumulation in vascular tissue.
J. Rutledge (1994)
Mechanisms by which lipoprotein lipase alters cellular metabolism of lipoprotein(a), low density lipoprotein, and nascent lipoproteins. Roles for low density lipoprotein receptors and heparan sulfate proteoglycans.
K. Williams (1992)
10.1172/JCI117195
Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein and scavenger receptor in human atherosclerotic lesions.
J. Luoma (1994)
10.1146/ANNUREV.BI.52.070183.001255
Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis.
M. Brown (1983)



This paper is referenced by
10.1016/S0008-6363(02)00405-4
The pivotal role of lipoprotein lipase in atherosclerosis.
J. R. Mead (2002)
10.1161/01.ATV.19.2.309
Tissue factor pathway inhibitor is expressed by human monocyte-derived macrophages : relationship to tissue factor induction by cholesterol and oxidized LDL.
L. Petit (1999)
Natural antibodies against phosphorylcholine as potential protective factors in atherosclerosis, cardiovascular disease and systemic lupus erythematosus
J. Su (2009)
10.1161/ATVBAHA.111.243519
Human ATP–Binding Cassette G1 Controls Macrophage Lipoprotein Lipase Bioavailability and Promotes Foam Cell Formation
M. Olivier (2012)
10.1007/s00109-004-0551-2
Chylomicron remnants and oxidised low density lipoprotein have differential effects on the expression of mRNA for genes involved in human macrophage foam cell formation
K. V. Batt (2004)
10.1186/1758-5996-2-13
Short-term nutritional counseling reduces body mass index, waist circumference, triceps skinfold and triglycerides in women with metabolic syndrome
G. D. Pimentel (2010)
10.1016/j.bbalip.2014.03.013
Physiological regulation of lipoprotein lipase.
S. Kersten (2014)
10.1093/NDT/GFM804
Dialysis-related systemic microinflammation is associated with specific genomic patterns.
G. Zaza (2008)
10.1152/PHYSREV.00005.2003
Role of monocytes in atherogenesis.
B. Osterud (2003)
10.1016/J.BBALIP.2004.03.002
Expression of the lysophospholipid receptor family and investigation of lysophospholipid-mediated responses in human macrophages.
C. Q. Duong (2004)
Macrophage lipoprotein lipase expression is increased in patients with heterozygous familial hypercholesterolemia.
M. Beauchamp (2002)
10.1016/J.FREERADBIOMED.2004.04.016
Thioredoxin reductase 1 is upregulated in atherosclerotic plaques: specific induction of the promoter in human macrophages by oxidized low-density lipoproteins.
C. Furman (2004)
10.1007/978-1-4419-9236-9_18
Native and minimally oxidized low density lipoprotein depress smooth muscle matrix metalloproteinase levels
David P. Wilson (2003)
Reactive Oxygen Species as Potential Mediators of Obesity-Related Cardiovascular Complications 35
Anca D Dobrian (2014)
10.1161/01.ATV.0000142366.69080.c3
REDD2 Gene Is Upregulated by Modified LDL or Hypoxia and Mediates Human Macrophage Cell Death
C. Cuaz-Pérolin (2004)
10.1161/01.CIR.103.8.1057
Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages
N. Ouchi (2001)
10.1016/S0021-9150(00)00398-1
Diabetic state induces lipid loading and altered expression and secretion of lipoprotein lipase in human monocyte-derived macrophages.
A. Dobrian (2000)
10.1007/s00109-002-0384-9
Lipoprotein lipase: structure, function, regulation, and role in disease
J. R. Mead (2002)
10.2217/17460875.3.6.637
Oxidized LDL and the metabolic syndrome.
P. Holvoet (2006)
10.6064/2012/205027
Stress in Obesity and Associated Metabolic and Cardiovascular Disorders
P. Holvoet (2012)
10.1016/j.jacc.2013.05.105
Elevated expression of lipoprotein-associated phospholipase A2 in calcific aortic valve disease: implications for valve mineralization.
A. Mahmut (2014)
10.1089/10979330152560487
Effects of differently oxidized LDL on the expression of pro-inflammatory molecules in human monocytes in vitro.
R. Dominaitiene (2001)
10.1007/8904_2013_272
Severe hypertriglyceridemia in a newborn with monogenic lipoprotein lipase deficiency: an unconventional therapeutic approach with exchange transfusion.
L. Pugni (2014)
10.1124/JPET.108.142950
Inhibition of LPS Stimulated COPD Macrophage Inflammatory Gene Expression by Dexamethasone and the p38 MAPK Inhibitor SB706504
Lauren M Kent (2008)
10.1023/A:1014721026280
17β-Estradiol Enhances the Flux of Cholesterol Through the Cholesteryl Ester Cycle in Human Macrophages
M. Napolitano (2001)
10.3181/00379727-231-2310766
Upregulation of Endothelin Receptor B in Human Endothelial Cells by Low-Density Lipoproteins
G. Muller (2006)
10.1016/S0014-5793(02)02223-8
Peroxisome proliferator‐activated receptor (PPAR) agonists decrease lipoprotein lipase secretion and glycated LDL uptake by human macrophages
F. Gbaguidi (2002)
10.1111/j.1600-6143.2006.01433.x
mTOR Inhibition Induces Endothelial Progenitor Cell Death
S. Miriuka (2006)
10.1016/S1388-1981(02)00355-4
VLDL-induced triglyceride accumulation in human macrophages is mediated by modulation of LPL lipolytic activity in the absence of change in LPL mass.
D. Milosavljevic (2003)
10.1016/S0021-9150(00)00634-1
Preferential reduction of very low density lipoprotein-1 particle number by fenofibrate in type IIB hyperlipidemia: consequences for lipid accumulation in human monocyte-derived macrophages.
D. Milosavljevic (2001)
10.1023/A:1024794924217
Native and minimally oxidized low density lipoprotein depress smooth muscle matrix metalloproteinase levels
David F Wilson (2003)
10.1016/J.NUT.2006.04.012
Postprandial serum triacylglycerols and oxidative stress in mice after consumption of fish oil, soy oil or olive oil: possible role for paraoxonase-1 triacylglycerol lipase-like activity.
B. Fuhrman (2006)
See more
Semantic Scholar Logo Some data provided by SemanticScholar