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Originally published In Press as doi:10.1074/jbc.M002423200 on June 16, 2000
J. Biol. Chem., Vol. 275, Issue 34, 26293-26299, August 25, 2000
Macrophage Lipoprotein Lipase Promotes Foam Cell Formation and
Atherosclerosis in Low Density Lipoprotein
Receptor-deficient Mice*
Vladimir R.
Babaev §,
Mayur B.
Patel,
Clay F.
Semenkovich¶,
Sergio
Fazio ** , and
MacRae F.
Linton  §§
From the Departments of Medicine, Pathology,
and §§ Pharmacology, Vanderbilt University Medical Center,
Nashville, Tennessee 37232 and ¶ Washington University,
St. Louis, Missouri 63110-1043
The role of macrophage lipoprotein
lipase (LPL) expression in atherosclerotic lesion formation was
examined in low density lipoprotein receptor
(LDLR / ) mice using dietary conditions designed to
induce either fatty streak lesions or complex atherosclerotic lesions.
First, LDLR / mice chimeric for macrophage LPL
expression were created by transplantation of lethally irradiated
female LDLR / mice with LPL /
(n = 12) or LPL+/+ (n = 14) fetal liver cells as a source of hematopoietic cells. To
induce fatty streak lesions, these mice were fed a Western diet for 8 weeks, resulting in severe hypercholesterolemia. There were no
differences in plasma post-heparin LPL activity, serum lipid levels, or
lipoprotein distribution between these two groups. The mean lesion area
in the proximal aorta in LPL / LDLR /
mice was significantly reduced by 33% compared with LPL+/+
LDLR / mice, and a similar reduction (38%) in
lesion area was found by en face analysis of the aortae. To
induce complex atherosclerotic lesions, female LDLR /
mice were lethally irradiated, transplanted with LPL /
(n = 14), LPL+/ (n = 13), or LPL+/+ (n = 14) fetal liver cells,
and fed the Western diet for 19 weeks. Serum cholesterol and
triglyceride levels did not differ between the three groups. After 19 weeks of diet, the lesions in the proximal aorta were complex with
relatively few macrophages expressing LPL protein and mRNA in
LPL+/+ LDLR / mice. Analysis of
cross-sections of the proximal aorta demonstrated no differences in the
extent of lesion area between the groups, whereas en face
analysis of the aortae revealed a dose-dependent effect of
macrophage LPL on mean aortic lesion area in LPL / LDLR / , LPL /+ LDLR / ,
and LPL+/+ LDLR / mice (1.8 ± 0.2%, 3.5 ± 0.5% and 5.9 ± 0.8%, respectively). Taken together, these data indicate that macrophage LPL expression in the
artery wall promotes atherogenesis during foam cell lesion formation,
but this impact may be limited to macrophage-rich lesions.
*
This work was supported in part by American Heart
Association Established Investigator Award 9740040N (to M. F. L.) and by National Institutes of Health Grants HL53989 and HL58427.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
§
Supported by Fellowship Award 9840052SE from the Southeast
Affiliate of the American Heart Association.
**
An American Heart Association Established Investigator (96001900).

To whom correspondence may be addressed: Division of
Cardiovascular Medicine, Vanderbilt University School of Medicine, Rm. 312, Medical Research Bldg. II, Nashville, TN 37232-6303. Tel.: 615-936-1653; Fax: 615-936-1667; E-mail:
macrae.linton@mcmail.vanderbilt.edu or
sergio.fazio@mcmail.vanderbilt.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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[PDF]
|
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|
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[Full Text]
[PDF]
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[Abstract]
[Full Text]
[PDF]
|
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|
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277(13):
11097 - 11106.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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456 - 461.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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J. Biol. Chem.,
February 8, 2002;
277(7):
5692 - 5697.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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[Abstract]
[Full Text]
[PDF]
|
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|
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|
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[Abstract]
[Full Text]
[PDF]
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[Abstract]
[Full Text]
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[Full Text]
[PDF]
|
 |
|
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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