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Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease.
Noz, Marlies P Bekkering, Siroon Groh, Laszlo Nielen, Tim Mj Lamfers, Evert Jp Schlitzer, Andreas El Messaoudi, Saloua van Royen, Niels Huys, Erik Hjpg Preijers, Frank Wmb
Noz, Marlies P
Bekkering, Siroon
Groh, Laszlo
Nielen, Tim Mj
Lamfers, Evert Jp
Schlitzer, Andreas
El Messaoudi, Saloua
van Royen, Niels
Huys, Erik Hjpg
Preijers, Frank Wmb
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2020-11-10
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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.
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Elife. 2020 Nov 10;9:e60939. doi: 10.7554/eLife.60939.
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en
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2050-084X