Department of Cardiology, Canisius Wilhelmina Hospital, Nijmegen, Netherlands
Andreas Schlitzer
Quantitative Systems Biology, Life & Medical Sciences Institute, University of Bonn, Single Cell Genomics and Epigenomics Unit at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany
Saloua El Messaoudi
Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands
Niels van Royen
Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands
Erik HJPG Huys
Department of Laboratory Medicine – Laboratory for Haematology, Radboud University Medical Center, Nijmegen, Netherlands
Frank WMB Preijers
Department of Laboratory Medicine – Laboratory for Haematology, Radboud University Medical Center, Nijmegen, Netherlands
Esther MM Smeets
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Netherlands
Erik HJG Aarntzen
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Netherlands
Bowen Zhang
Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
Yang Li
Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
Manita EJ Bremmers
Department of Haematology, Radboud University Medical Center, Nijmegen, Netherlands
Walter JFM van der Velden
Department of Haematology, Radboud University Medical Center, Nijmegen, Netherlands
Harry Dolstra
Department of Laboratory Medicine – Laboratory for Haematology, Radboud University Medical Center, Nijmegen, Netherlands
Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
Marc E Gomes
Department of Cardiology, Canisius Wilhelmina Hospital, Nijmegen, Netherlands
Mihai G Netea
Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands; Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany
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.
