Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease
- Radboud University Medical Center, Netherlands
- Radboud University, Netherlands
- Canisius Wilhelmina Hospital, Netherlands
- University of Bonn, Germany
- Hannover Medical School, Germany
- 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
Niels Peter Riksen
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.
Reviewing Editor
- Noriaki Emoto, Kobe Pharmaceutical University, Japan
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).
Version history
- Received: July 10, 2020
- Accepted: October 27, 2020
- Accepted Manuscript published: November 10, 2020 (version 1)
- Version of Record published: November 13, 2020 (version 2)
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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Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease
eLife 9:e60939.
https://doi.org/10.7554/eLife.60939
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