Retrovirus-mediated Expression of Apolipoprotein A-I in the Macrophage Protects against Atherosclerosis in Vivo

Hiroyuki Ishiguro, Hiroaki Yoshida, Amy S. Major, Tianli Zhu, Vladimir R. Babaev, MacRae F. Linton, Sergio Fazio

    Research output: Contribution to journalArticle

    43 Scopus citations

    Abstract

    We have previously reported that the lack of apolipoprotein (apo) E expression by macrophages promotes foam cell formation in vivo. Because transgenic mice overexpressing human apoA-I from the liver (h-apoA-I TgN) are protected from the atherogenesis induced by apoE deficiency, we hypothesized that the presence of apoA-I in the vessel wall could reduce the negative effect of apoE deficiency on lesion growth. To address this issue, we used both retroviral transduction and transgenic approaches to produce in vivo systems where apoA-I is expressed from macrophages. In the retroviral transduction study, apoA-I-deficient (apoA-I-/-) mice reconstituted with apoE-deficient (apoE-/-) bone marrow cells that were infected with a retroviral vector expressing human apoA-I (MFG-HAI) had 95% lower atherosclerotic lesion area than that of recipients of apoE-/- bone marrow cells infected with the parental virus (MFG). To determine whether the protective effect of locally produced apoA-I was due to the lack of systemic apoA-I, we conducted a different experiment using h-apoA-I TgN mice as recipients of apoE-/- bone marrow with or without human apoA-I (driven by a macrophage-specific transgene defined as mφ-AI). Aortic lesion area in apoE-/-/mφ-AI → h-apoA-I TgN mice was decreased by 85% compared with apoE-/- → h-apoA-I TgN mice. These data demonstrate that expression of apoA-I from macrophages protects against atherogenesis without affecting plasma apoA-I and high density lipoprotein cholesterol levels.

    Original languageEnglish (US)
    Pages (from-to)36742-36748
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume276
    Issue number39
    DOIs
    StatePublished - Sep 28 2001

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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