← Back to Search
Role Of Macrophage-Derived Lipoprotein Lipase In Lipoprotein Metabolism And Atherosclerosis
M. van Eck, R. Zimmermann, P. Groot, R. Zechner, T. V. van Berkel
Published 2000 · Biology, Medicine
Download PDFAnalyze on Scholarcy
Lipoprotein lipase (LPL) synthesis by macrophages is upregulated in early atherogenesis, implicating the possible involvement of LPL in plaque formation. However, it is still unclear whether macrophage-derived LPL displays a proatherosclerotic or an antiatherosclerotic role in atherosclerotic lesion development. In this study, the role of macrophage-derived LPL on lipid metabolism and atherosclerosis was assessed in vivo by transplantation of LPL-deficient (LPL−/−) and wild-type (LPL+/+) bone marrow into C57BL/6 mice. Eight weeks after bone marrow transplantation (BMT), serum cholesterol levels in LPL−/−→C57BL/6 mice were reduced by 8% compared with those in LPL+/+→C57BL/6 mice (P <0.05, n=16), whereas triglycerides were increased by 33% (P <0.05, n=16). Feeding the mice a high-cholesterol diet increased serum cholesterol levels in LPL−/−→C57BL/6 and LPL+/+→C57BL/6 mice 5-fold and 9-fold, respectively, resulting in a difference of ≈50% (P <0.01) after 3 months on the diet. No effects on triglyceride levels were observed under these conditions. Furthermore, serum apolipoprotein E levels were reduced by 50% in the LPL−/−→C57BL/6 mice compared with controls under both dietary conditions. After 3 months on a high-cholesterol diet, the atherosclerotic lesion area in LPL−/−→C57BL/6 mice was reduced by 52% compared with controls. It can be concluded that macrophage-derived LPL plays a significant role in the regulation of serum cholesterol, apolipoprotein E, and atherogenesis, suggesting that specific blockade of macrophage LPL production may be beneficial for decreasing atherosclerotic lesion development. (Arterioscler Thromb Vasc Biol. 2000;20:e53-e62.)
This paper references
Effects of heterozygous lipoprotein lipase deficiency on diet-induced atherosclerosis in mice.
C. Semenkovich (1998)
The novel compound NO-1886 elevates plasma high-density lipoprotein cholesterol levels in hamsters and rabbits by increasing lipoprotein lipase without any effect on cholesteryl ester transfer protein activity.
K. Tsutsumi (1997)
The tissue-specific expression of lipoprotein lipase: implications for energy and lipoprotein metabolism.
R. Zechner (1997)
Overexpression of human lipoprotein lipase in transgenic mice. Resistance to diet-induced hypertriglyceridemia and hypercholesterolemia.
M. Shimada (1993)
Mouse models of atherosclerosis.
J. Smith (1998)
Separation of plasma lipoproteins by density-gradient ultracentrifugation.
T. Redgrave (1975)
Accelerated atherosclerosis in C57Bl/6 mice transplanted with ApoE-deficient bone marrow.
M. van Eck (2000)
in C 57 BL / 6 mice transplanted with apoE - deficient bone marrow
S Fazio (2000)
Bone marrow transplantation in apolipoprotein E-deficient mice. Effect of ApoE gene dosage on serum lipid concentrations, (beta)VLDL catabolism, and atherosclerosis.
M. van Eck (1997)
New aspects on the role of plasma lipases in lipoprotein catabolism and atherosclerosis.
U. Beisiegel (1996)
Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy characterized by proliferation of mitochondria and peroxisomes in transgenic mice.
S. Levak-Frank (1995)
Regulation by nutritional status of lipids and apolipoproteins A-I, A-II, and A-IV in inbred mice.
R. Leboeuf (1994)
Lipoprotein lipase and hepatic lipase
P. Kern (1991)
Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by bone marrow transplantation.
W. Boisvert (1995)
Macrophages and smooth muscle cells express lipoprotein lipase in human and rabbit atherosclerotic lesions.
S. Ylä-Herttuala (1991)
Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo.
V. Babaev (1999)
3.P.183 Bone marrow transplantation in apolipoprotein E deficient mice: Effect of apoE gene-dosage on serum lipid concentrations, βVLDL catabolism, and atherosclerosis
M. V. Eck (1997)
Correction of Hypertriglyceridemia with Low High-Density Lipoprotein Cholesterol by the Novel Compound NO-1886, a Lipoprotein Lipase-Promoting Agent, in STZ-Induced Diabetic Rats
K. Tsutsumi (1995)
Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation
M. Linton (1995)
Secretion of lipoprotein lipase by macrophages in culture.
J. C. Khoo (1981)
Lipoprotein lipase enhances human monocyte adhesion to aortic endothelial cells.
J. Mamputu (1997)
Synthetic low and high fat diets for the study of atherosclerosis in the mouse.
P. Nishina (1990)
Efficient Trace-labelling of Proteins with Iodine
A. McFarlane (1958)
Quantitative assessment of aortic atherosclerosis in APOE*3 Leiden transgenic mice and its relationship to serum cholesterol exposure.
P. Groot (1996)
Abundant expression of apoprotein E by macrophages in human and rabbit atherosclerotic lesions.
M. Rosenfeld (1993)
Structure, function and role of lipoprotein lipase in lipoprotein metabolism.
S. Santamarina-Fojo (1994)
Lipoprotein Lipase Reduces Secretion of Apolipoprotein E from Macrophages*
M. Lucas (1997)
In vivo and in vitro uptake and degradation of acetylated low density lipoprotein by rat liver endothelial, Kupffer, and parenchymal cells.
J. Nagelkerke (1983)
Lipoprotein lipase (LpL) affects low density lipoprotein (LDL) flux through vascular tissue: evidence that LpL increases LDL accumulation in vascular tissue.
J. Rutledge (1994)
Lipoprotein lipase is synthesized by macrophage-derived foam cells in human coronary atherosclerotic plaques.
K. O'brien (1992)
Rapid and simple isolation procedure for lipoprotein lipase from human milk.Biochim
R. Zechner (1990)
Induced Mutant Mice Expressing Lipoprotein Lipase Exclusively in Muscle Have Subnormal Triglycerides yet Reduced High Density Lipoprotein Cholesterol Levels in Plasma*
S. Levak-Frank (1997)
Rapid and simple isolation procedure for lipoprotein lipase from human milk.
R. Zechner (1990)
Lipoprotein lipase and hepatic lipase.Curr Opin Lipidol
T Olivecrona (1993)
Synthesis of Apolipoprotein E by Peripheral Tissues
D. Williams (1985)
Lipoprotein lipase and hepatic lipase mRNA tissue specific expression, developmental regulation, and evolution.
C. Semenkovich (1989)
Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes.
P. Weinstock (1995)
Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets.
N. Elshourbagy (1985)
Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV.
R. D. Cohen (1997)
The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis.
K. Tsutsumi (1993)
Decreased Atherosclerosis in Heterozygous Low Density Lipoprotein Receptor-deficient Mice Expressing the Scavenger Receptor BI Transgene*
T. Arai (1999)
COOH-terminal Disruption of Lipoprotein Lipase in Mice Is Lethal in Homozygotes, but Heterozygotes Have Elevated Triglycerides and Impaired Enzyme Activity (*)
T. Coleman (1995)
IFCC method for alanine aminotransferase
K. Henley (1980)
Lipoprotein lipase increases low density lipoprotein retention by subendothelial cell matrix.
U. Saxena (1992)
Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis.
I. Goldberg (1996)
High macrophage lipoprotein lipase expression and secretion are associated in inbred murine strains with susceptibility to atherosclerosis.
G. Renier (1993)
Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase.
M. Shimada (1996)
Adenovirus-mediated gene transfer of human lipoprotein lipase ameliorates the hyperlipidemias associated with apolipoprotein E and LDL receptor deficiencies in mice.
E. Zsigmond (1997)
Immunoreactive apolipoprotein E is a widely distributed cellular protein. Immunohistochemical localization of apolipoprotein E in baboon tissues.
C. Lin (1986)
Apolipoprotein E and lipoprotein lipase secreted from human monocyte-derived macrophages modulate very low density lipoprotein uptake.
S. Ishibashi (1990)
Lipoprotein lipase increases lipoprotein binding to the artery wall and increases endothelial layer permeability by formation of lipolysis products.
J. Rutledge (1997)
Muscle-specific overexpression of lipoprotein lipase in transgenic mice results in increased alpha-tocopherol levels in skeletal muscle.
W. Sattler (1996)
Synthesis of apolipoprotein E by peripheral tissues. Potential functions in reverse cholesterol transport and cellular cholesterol metabolism.
D. Williams (1985)
Protein measurement with the Folin phenol reagent.
O. H. Lowry (1951)
Regulation of lipoprotein lipase secretion in murine macrophages during foam cell formation in vitro. Effect of triglyceride-rich lipoproteins.
O. Sofer (1992)
Lipoprotein lipase enhances the interaction of low density lipoproteins with artery-derived extracellular matrix proteoglycans.
I. J. Edwards (1993)
IFCC method for alanine aminotransferase.J
HU Bergmeyer (1986)
Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages.
S. Fazio (1997)
This paper is referenced by
Betulinic acid downregulates expression of oxidative stress-induced lipoprotein lipase via the PKC/ERK/c-Fos pathway in RAW264.7 macrophages.
J. Peng (2015)
Overexpression of Angiopoietin-Like Protein 4 Protects Against Atherosclerosis Development
Anastasia Georgiadi (2013)
Amelioration of Hypertriglyceridemia with Hypo-Alpha-Cholesterolemia in LPL Deficient Mice by Hematopoietic Cell-Derived LPL
Yinyuan Ding (2011)
Endothelial lipase enhances low density lipoprotein binding and cell association in THP-1 macrophages.
Guosong Qiu (2007)
Effects of High Sugar Consumption on Transcriptome of Adipose Tissues and Metabolome of Blood in Mice
M. Park (2008)
Thematic review series: The Immune System and Atherogenesis. Cytokine regulation of macrophage functions in atherogenesis Published, JLR Papers in Press, July 1, 2005. DOI 10.1194/jlr.R500009-JLR200
A. Daugherty (2005)
Association of the Hindiii and S447X Polymorphisms in Lpl Gene with Hypertension and Type 2 Diabetes in Mexican Families
Salvador Muñoz-Barrios (2012)
The role of lipoprotein lipase in adipose tissue development and metabolism
R. Zechner (2000)
Human ATP–Binding Cassette G1 Controls Macrophage Lipoprotein Lipase Bioavailability and Promotes Foam Cell Formation
M. Olivier (2012)
Angiopoietin-like 4: A double-edged sword in atherosclerosis and ischemic stroke?
Longchang Xu (2015)
Arterial function parameters in patients with metabolic syndrome and severe hypertriglyceridemia.
Egidija Rinkūnienė (2017)
Triglycerides Revisited to the Serial.
Paulo Ricardo Nazário Viecili (2017)
Systemic inflammation as a cardiovascular disease risk factor and as a potential target for drug therapy.
R. Kaplan (2001)
Phospholipid transfer protein is present in human atherosclerotic lesions and is expressed by macrophages and foam cells Published, JLR Papers in Press, May 1, 2003. DOI 10.1194/jlr.M200281-JLR200
C. Desrumaux (2003)
Upregulation of Macrophage Endothelial Lipase by Toll-Like Receptors 4 and 3 Modulates Macrophage Interleukin-10 and -12 Production
X. Wang (2007)
MicroRNA‐29a regulates pro‐inflammatory cytokine secretion and scavenger receptor expression by targeting LPL in oxLDL‐stimulated dendritic cells
T. Chen (2011)
Triglyceride and Cardiovascular Disease
M. Kim (2013)
Human gene array analysis of THP-1 macrophages exposed to lipoprotein hydrolysis products generated by lipoprotein lipase
Narmadaa Thyagarajan (2017)
Advanced glycation end products potentiate the stimulatory effect of glucose on macrophage lipoprotein lipase expression Published, JLR Papers in Press, June 21, 2004. DOI 10.1194/jlr.M400169-JLR200
M. Beauchamp (2004)
Epanova(®) and hypertriglyceridemia: pharmacological mechanisms and clinical efficacy.
Y. Kataoka (2013)
Regulation of In Vitro Vascular Calcification by BMP4, VEGF and Wnt3a
L. Mikhaylova (2007)
A new piece in the puzzling effect of n-3 fatty acids on atherosclerosis?
W Le Goff (2014)
The pivotal role of lipoprotein lipase in atherosclerosis.
J. R. Mead (2002)
Direct effects of long-chain non-esterified fatty acids on vascular cells and their relevance to macrovascular complications of diabetes.
J. Oram (2004)
A new piece in the puzzling effect of n-3 fatty acids on atherosclerosis?
Wilfried Le Goff (2014)
Active autophagy but not lipophagy in macrophages with defective lipolysis
M. Goeritzer (2015)
Macrophage Adipose Triglyceride Lipase Deficiency Attenuates Atherosclerotic Lesion Development in Low-Density Lipoprotein Receptor Knockout Mice
B. Lammers (2011)
Regulation of lipoprotein lipase by Angptl4
Wieneke Dijk (2014)
Physiological regulation of lipoprotein lipase.
S. Kersten (2014)
miR-467b regulates the cholesterol ester formation via targeting ACAT1 gene in RAW 264.7 macrophages.
Bo Wang (2017)
Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association.
M. Miller (2011)
Lipoprotein lipase: from gene to atherosclerosis.
Y. Li (2014)See more