Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease
Marlies P Noz1, Siroon Bekkering1, Laszlo Groh1
1Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands.
Insights
Immune cell activation in atherosclerosis begins in myeloid progenitors, not just mature cells. This discovery in coronary artery disease patients offers new avenues for treating cardiovascular disease.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Cell Biology
Background:
- Atherosclerosis, a primary cause of cardiovascular disease (CVD), involves hyperinflammatory leukocytes, particularly monocyte-derived macrophages, within plaques.
- Existing understanding suggests inflammation arises from mature immune cells, but the origin of this hyperinflammatory state remains unclear.
Purpose of the Study:
- To investigate whether immune cell reprogramming in patients with atherosclerotic CVD originates at the myeloid progenitor level.
- To explore metabolic and transcriptional changes in immune cells from patients with coronary artery disease compared to healthy controls.
Main Methods:
- Comparative analysis of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs from 13 atherosclerosis patients and 13 controls.
- Ex vivo cytokine production capacity assessment post-stimulation.
- Analysis of bone marrow cell composition, glycolysis, oxidative phosphorylation, and transcriptome of hematopoietic stem cell/granulocyte-monocyte progenitor (HSC/GMP) populations.
Main Results:
- Patients with atherosclerosis exhibited heightened cytokine production from both peripheral blood MNCs and bone marrow MNCs.
- Bone marrow MNCs from these patients showed increased glycolysis and oxidative phosphorylation.
- Bone marrow composition was skewed towards myelopoiesis, with HSC/GMP populations enriched in neutrophil- and monocyte-related pathways.
Conclusions:
- Innate immune cell activation in atherosclerosis patients initiates at the myeloid progenitor stage.
- This progenitor-level reprogramming presents novel therapeutic targets for cardiovascular disease treatment.
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.
Related Concept Videos
01:21Stem Cell Therapy for Tissue Regeneration
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
01:15Differentiation of Common Myeloid Progenitor Cells
01:22Bone Marrow Sampling and Transplants
The transplant begins with high doses of chemotherapy and radiation treatment, which aim to destroy...