Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis

Liza Makowski, Jeffrey B. Boord, Kazuhisa Maeda, Vladimir R. Babaev, K. Teoman Uysal, Maureen A. Morgan, Rex A. Parker, Jill Suttles, Sergio Fazio, Gökhan S. Hotamisligil, MacRae F. Linton

    Research output: Contribution to journalArticle

    498 Scopus citations

    Abstract

    The adipocyte fatty-acid-binding protein, aP2, has an important role in regulating systemic insulin resistance and lipid metabolism. Here we demonstrate that aP2 is also expressed in macrophages, has a significant role in their biological responses and contributes to the development of atherosclerosis. Apolipoprotein E (ApoE)-deficient mice also deficient for aP2 showed protection from atherosclerosis in the absence of significant differences in serum lipids or insulin sensitivity. aP2-deficient macrophages showed alterations in inflammatory cytokine production and a reduced ability to accumulate cholesterol esters when exposed to modified lipoproteins. Apoe-/- mice with Ap2+/+ adipocytes and Ap2-/- macrophages generated by bone-marrow transplantation showed a comparable reduction in atherosclerotic lesions to those with total aP2 deficiency, indicating an independent role for macrophage aP2 in atherogenesis. Through its distinct actions in adipocytes and macrophages, aP2 provides a link between features of the metabolic syndrome and could be a new therapeutic target for the prevention of atherosclerosis.

    Original languageEnglish (US)
    Pages (from-to)699-705
    Number of pages7
    JournalNature medicine
    Volume7
    Issue number6
    DOIs
    StatePublished - 2001

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Makowski, L., Boord, J. B., Maeda, K., Babaev, V. R., Uysal, K. T., Morgan, M. A., Parker, R. A., Suttles, J., Fazio, S., Hotamisligil, G. S., & Linton, M. F. (2001). Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nature medicine, 7(6), 699-705. https://doi.org/10.1038/89076