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Toll-like receptor 2 plays a critical role in the progression of atherosclerosis that is independent of dietary lipids

  • Author Footnotes
    1 These authors contributed equally to this work.
    Xinyan Liu
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Takashi Ukai
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States

    Department of Periodontology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan
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  • Hiromichi Yumoto
    Affiliations
    Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States

    Department of Conservative Dentistry, The Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan
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  • Michael Davey
    Affiliations
    Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, United States
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  • Sulip Goswami
    Affiliations
    Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States
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  • Frank C. Gibson III
    Affiliations
    Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States
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  • Caroline A. Genco
    Correspondence
    Corresponding author. Tel.: +1 617 414 5305; fax: +1 617 414 4149.
    Affiliations
    Department of Medicine, Section of Molecular Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, United States

    Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, United States

    Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, United States
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Abstract

      Objective

      Toll-like receptors (TLRs), a group of pathogen-associated microbial pattern recognition receptors, play an important role in innate immune signaling and are differentially regulated in chronic inflammatory diseases such as atherosclerosis. However, the involvement of TLRs in the progression of atherosclerosis is still unclear.

      Methods and results

      TLR2 and apolipoprotein E double knockout (Tlr2−/−Apoe−/−) mice were generated and the progressive formation of atherosclerotic plaque in the aortas was examined in mice fed a normal chow diet. We demonstrate that inactivation of TLR2 resulted in reduced progression of atherosclerosis in both male and female Apoe−/− mice. Likewise, TLR2 deficiency resulted in a reduction in lipid accumulation and decreased macrophage recruitment to the aortic sinus, as well as reduced monocyte chemoattractant protein-1 (MCP-1) levels. Furthermore, macrophages isolated from Tlr2−/−Apoe−/− mice demonstrated significantly reduced MCP-1 production upon stimulation with a TLR2 ligand. However, no differences in acetylated low-density lipoprotein uptake and foam cell formation were observed in macrophages isolated from Tlr2−/−Apoe−/− mice as compared to Apoe−/− mice.

      Conclusions

      TLR2 plays a critical role in the progression of atherosclerosis in Apoe−/− mice, which is independent of dietary lipids and macrophage lipid uptake.

      Keywords

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