Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease.
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AuthorsNoz, Marlies P
Nielen, Tim Mj
Lamfers, Evert Jp
El Messaoudi, Saloua
van Royen, Niels
Huys, Erik Hjpg
Preijers, Frank Wmb
Smeets, Esther Mm
Aarntzen, Erik Hjg
Bremmers, Manita Ej
van der Velden, Walter Jfm
Joosten, Leo Ab
Gomes, Marc E
Netea, Mihai G
Riksen, Niels P
MetadataShow full item record
AbstractAtherosclerosis 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.
CitationElife. 2020 Nov 10;9:e60939. doi: 10.7554/eLife.60939.
AffiliationCiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.
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