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

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 () and Liwu Li ()
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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

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13436

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DOI: 10.1038/ncomms13436

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