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The persistence of low-grade inflammatory monocytes contributes to aggravated atherosclerosis

Author

Listed:
  • Shuo Geng

    (Virginia Tech)

  • Keqiang Chen

    (Virginia Tech)

  • Ruoxi Yuan

    (Virginia Tech)

  • Liang Peng

    (Immunology Institute, Icahn School of Medicine at Mount Sinai)

  • Urmila Maitra

    (Virginia Tech)

  • Na Diao

    (Virginia Tech)

  • Chun Chen

    (Virginia Tech)

  • Yao Zhang

    (Virginia Tech)

  • Yuan Hu

    (Immunology Institute, Icahn School of Medicine at Mount Sinai)

  • Chen-Feng Qi

    (Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Susan Pierce

    (Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Wenhua Ling

    (School of Public Health, National Sun Yat-Sen University)

  • Huabao Xiong

    (Immunology Institute, Icahn School of Medicine at Mount Sinai)

  • Liwu Li

    (Virginia Tech)

Abstract

Sustained low-grade inflammation mediated by non-resolving inflammatory monocytes has long been suspected in the pathogenesis of atherosclerosis; however, the molecular mechanisms responsible for the sustainment of non-resolving inflammatory monocytes during atherosclerosis are poorly understood. Here we observe that subclinical endotoxemia, often seen in humans with chronic inflammation, aggravates murine atherosclerosis through programming monocytes into a non-resolving inflammatory state with elevated Ly6C, CCR5, MCP-1 and reduced SR-B1. The sustainment of inflammatory monocytes is due to the disruption of homeostatic tolerance through the elevation of miR-24 and reduction of the key negative-feedback regulator IRAK-M. miR-24 reduces the levels of Smad4 required for the expression of IRAK-M and also downregulates key lipid-processing molecule SR-B1. IRAK-M deficiency in turn leads to elevated miR-24 levels, sustains disruption of monocyte homeostasis and aggravates atherosclerosis. Our data define an integrated feedback circuit in monocytes and its disruption may lead to non-resolving low-grade inflammation conducive to atherosclerosis.

Suggested Citation

  • Shuo Geng & Keqiang Chen & Ruoxi Yuan & Liang Peng & Urmila Maitra & Na Diao & Chun Chen & Yao Zhang & Yuan Hu & Chen-Feng Qi & Susan Pierce & Wenhua Ling & Huabao Xiong & Liwu Li, 2016. "The persistence of low-grade inflammatory monocytes contributes to aggravated atherosclerosis," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13436
    DOI: 10.1038/ncomms13436
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