Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease

  1. Marlies Noz
  2. Siroon Bekkering
  3. Laszlo Groh
  4. Tim Nielen
  5. Evert Lamfers
  6. Andreas Schlitzer
  7. Saloua El Messaoudi
  8. Niels van Royen
  9. Erik Huys
  10. Frank Preijers
  11. Esther Smeets
  12. Erik Aarntzen
  13. Bowen Zhang
  14. Yang Li
  15. Manita Bremmers
  16. Walter van der Velden
  17. Harry Dolstra
  18. Leo AB Joosten
  19. Marc E Gomes
  20. Mihai G Netea
  21. Niels Peter Riksen  Is a corresponding author
  1. Radboud University Medical Center, Netherlands
  2. Radboud University, Netherlands
  3. Canisius Wilhelmina Hospital, Netherlands
  4. University of Bonn, Germany
  5. Hannover Medical School, Germany
  6. Radboud University Nijmegen Medical Centre, Netherlands

Abstract

Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, leukocytes have a hyperinflammatory phenotype. We hypothesize that immune cell reprogramming in these patients occurs at the level of myeloid progenitors. We included 13 patients with coronary artery disease due to severe atherosclerosis and 13 subjects without atherosclerosis in an exploratory study. Cytokine production capacity after ex vivo stimulation of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs was higher in patients with atherosclerosis. In BM-MNCs this was associated with increased glycolysis and oxidative phosphorylation. The BM composition was skewed towards myelopoiesis and transcriptome analysis of HSC/GMP cell populations revealed enrichment of neutrophil- and monocyte-related pathways. These results show that in patients with atherosclerosis, activation of innate immune cells occurs at the level of myeloid progenitors, which adds exciting opportunities for novel treatment strategies.

Data availability

RNA-seq data have been deposited in the ArrayExpress database at EMBL-EBI (www.ebi.ac.uk/arrayexpress)under accession number E-MTAB-9399

Article and author information

Author details

  1. Marlies Noz

    Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Siroon Bekkering

    Internal Medicine, Radboud University, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1149-466X
  3. Laszlo Groh

    Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Tim Nielen

    Cardiology, Canisius Wilhelmina Hospital, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7762-5912
  5. Evert Lamfers

    Cardiology, Canisius Wilhelmina Hospital, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5582-3720
  6. Andreas Schlitzer

    University of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Saloua El Messaoudi

    Cardiology, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Niels van Royen

    Cardiology, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  9. Erik Huys

    Laboratory medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Frank Preijers

    Laboratory medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Esther Smeets

    Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  12. Erik Aarntzen

    Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  13. Bowen Zhang

    Department of Computational Biology for Individualised Infection Medicine, Hannover Medical School, Hannover, Germany
    Competing interests
    The authors declare that no competing interests exist.
  14. Yang Li

    Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  15. Manita Bremmers

    Haematology, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  16. Walter van der Velden

    Haematology, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  17. Harry Dolstra

    Laboratory medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  18. Leo AB Joosten

    Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6166-9830
  19. Marc E Gomes

    Cardiology, Canisius Wilhelmina Hospital, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  20. Mihai G Netea

    Haematology, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  21. Niels Peter Riksen

    Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    For correspondence
    niels.riksen@radboudumc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9197-8124

Funding

European Unions Horizon 2020 (667837)

  • Leo AB Joosten
  • Mihai G Netea
  • Niels Peter Riksen

Netherlands Organisation for Scientific Research (NWO SPI 94-212)

  • Mihai G Netea

European Commission (833247)

  • Mihai G Netea

ERA-NET (2018T093)

  • Niels Peter Riksen

Netherlands Organisation for Scientic Research (452173113)

  • Siroon Bekkering

Hartstichting (2018T028)

  • Siroon Bekkering

Hartstichting (CVON2018-27)

  • Leo AB Joosten
  • Mihai G Netea
  • Niels Peter Riksen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Informed consent was obtained for all participants.The study protocol was approved by the Institutional Review Board Arnhem/Nijmegen, the Netherlands and registered at the ClinicalTrials.gov (NCT03172507).

Copyright

© 2020, Noz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Marlies Noz
  2. Siroon Bekkering
  3. Laszlo Groh
  4. Tim Nielen
  5. Evert Lamfers
  6. Andreas Schlitzer
  7. Saloua El Messaoudi
  8. Niels van Royen
  9. Erik Huys
  10. Frank Preijers
  11. Esther Smeets
  12. Erik Aarntzen
  13. Bowen Zhang
  14. Yang Li
  15. Manita Bremmers
  16. Walter van der Velden
  17. Harry Dolstra
  18. Leo AB Joosten
  19. Marc E Gomes
  20. Mihai G Netea
  21. Niels Peter Riksen
(2020)
Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease
eLife 9:e60939.
https://doi.org/10.7554/eLife.60939

Share this article

https://doi.org/10.7554/eLife.60939

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