A Direct Role for the Macrophage Low Density Lipoprotein Receptor in Atherosclerotic Lesion Formation
To evaluate the contribution of the macrophage low density lipoprotein receptor (LDLR) to atherosclerotic lesion formation, we performed bone marrow transplantation studies in different mouse strains. First, LDLR(â/â) mice were transplanted with either LDLR(+/+) marrow or LDLR(â/â) marrow an...
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Published in | The Journal of biological chemistry Vol. 274; no. 27; pp. 19204 - 19210 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
02.07.1999
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Subjects | |
Online Access | Get full text |
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Summary: | To evaluate the contribution of the macrophage low density lipoprotein receptor (LDLR) to atherosclerotic lesion formation,
we performed bone marrow transplantation studies in different mouse strains. First, LDLR(â/â) mice were transplanted with
either LDLR(+/+) marrow or LDLR(â/â) marrow and were challenged with an atherogenic Western type diet. The diet caused severe
hypercholesterolemia of a similar degree in the two groups, and no differences in the aortic lesion area were detected. Thus,
macrophage LDLR expression does not influence foam cell lesion formation in the setting of extreme LDL accumulation. To determine
whether macrophage LDLR expression affects foam cell formation under conditions of moderate, non-LDL hyperlipidemia, we transplanted
C57BL/6 mice with either LDLR(â/â) marrow (experimental group) or LDLR(+/+) marrow (controls). Cholesterol levels were not
significantly different between the two groups at baseline or after 6 weeks on a butterfat diet, but were 40% higher in the
experimental mice after 13 weeks, mostly due to accumulation of β-very low density lipoprotein (β-VLDL). Despite the increase
in cholesterol levels, mice receiving LDLR(â/â) marrow developed 63% smaller lesions than controls, demonstrating that macrophage
LDLR affects the rate of foam cell formation when the atherogenic stimulus is β-VLDL. We conclude that the macrophage LDLR
is responsible for a significant portion of lipid accumulation in foam cells under conditions of dietary stress. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.27.19204 |