Review Article | Published:

Regulation of macrophage immunometabolism in atherosclerosis

Nature Immunologyvolume 19pages526537 (2018) | Download Citation

Abstract

After activation, cells of the myeloid lineage undergo robust metabolic transitions, as well as discrete epigenetic changes, that can dictate both ongoing and future inflammatory responses. In atherosclerosis, in which macrophages play central roles in the initiation, growth, and ultimately rupture of arterial plaques, altered metabolism is a key feature that dictates macrophage function and subsequent disease progression. This Review explores how factors central to the plaque microenvironment (for example, altered cholesterol metabolism, oxidative stress, hypoxia, apoptotic and necrotic cells, and hyperglycemia) shape the metabolic rewiring of macrophages in atherosclerosis as well as how these metabolic shifts in turn alter macrophage immune-effector and tissue-reparative functions. Finally, this overview offers insight into the challenges and opportunities of harnessing metabolism to modulate aberrant macrophage responses in disease.

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Acknowledgements

Work in the laboratory of K.J.M. related to this review was supported by the National Institutes of Health (R35HL135799 and P01HL131481). G.J.K. was supported by a doctoral foreign study award from the Canadian Institutes of Health Research. E.E. was supported by an European Research Council Starting Grant (336643).

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Affiliations

  1. Department of Medicine, Marc and Ruti Bell Program for Vascular Biology and Disease, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA

    • Graeme J. Koelwyn
    • , Emma M. Corr
    •  & Kathryn J. Moore
  2. Department of Medicine, Heart Institute & Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA, USA

    • Ebru Erbay
  3. Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey

    • Ebru Erbay
  4. National Nanotechnology Center, Bilkent University, Ankara, Turkey

    • Ebru Erbay

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The authors declare no competing interests.

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Correspondence to Kathryn J. Moore.

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https://doi.org/10.1038/s41590-018-0113-3