Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL

Hagai Tavori, Yan Ru Su, Patricia G. Yancey, Ilaria Giunzioni, Ashley J. Wilhelm, John L. Blakemore, Manal Zabalawi, MacRae F. Linton, Mary G. Sorci-Thomas, Sergio Fazio

    Research output: Contribution to journalArticle

    15 Scopus citations

    Abstract

    Tissue cholesterol accumulation, macrophage infiltration, and inflammation are features of atherosclerosis and some forms of dermatitis. HDL and its main protein, apoAI, are acceptors of excess cholesterol from macrophages; this process inhibits tissue inflammation. Recent epidemiologic and clinical trial evidence questions the role of HDL and its manipulation in cardiovascular disease. We investigated the effect of ectopic macrophage apoAI expression on atherosclerosis and dermatitis induced by the combination of hypercholesterolemia and absence of HDL in mice. Hematopoietic progenitor cells were transduced to express human apoAI and transplanted into lethally irradiated LDL receptor-/-/apoAI-/- mice, which were then placed on a high-fat diet for 16 weeks. Macrophage apoAI expression reduced aortic CD4+ T-cell levels (-39.8%), lesion size (-25%), and necrotic core area (-31.6%), without affecting serum HDL or aortic macrophage levels. Macrophage apoAI reduced skin cholesterol by 39.8%, restored skin morphology, and reduced skin CD4+ T-cell levels. Macrophage apoAI also reduced CD4+ T-cell levels (-32.9%) in skin-draining lymph nodes but had no effect on other T cells, B cells, dendritic cells, or macrophages compared with control transplanted mice. Thus, macrophage apoAI expression protects against atherosclerosis and dermatitis by reducing cholesterol accumulation and regulating CD4+ T-cell levels, without affecting serum HDL or tissue macrophage levels.

    Original languageEnglish (US)
    Pages (from-to)635-643
    Number of pages9
    JournalJournal of Lipid Research
    Volume56
    Issue number3
    DOIs
    Publication statusPublished - Mar 1 2015

      Fingerprint

    Keywords

    • Apolipoprotein AI
    • Bone marrow transplant
    • Gene therapy
    • Hematopoietic progenitor cells
    • High density lipoprotein

    ASJC Scopus subject areas

    • Biochemistry
    • Cell Biology
    • Endocrinology

    Cite this