A direct role for the macrophage low density lipoprotein receptor in atherosclerotic lesion formation

MacRae F. Linton, Vladimir R. Babaev, Linda A. Gleaves, Sergio Fazio

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    73 Scopus citations

    Abstract

    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(-/-) mice were transplanted with either LDLR(+/+) marrow or LDLR(-/-) 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(-/-) 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(-/-) 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.

    Original languageEnglish (US)
    Pages (from-to)19204-19210
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume274
    Issue number27
    DOIs
    StatePublished - Jul 2 1999

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    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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