Monocyte/Macrophage Suppression in CD11b Diphtheria Toxin Receptor Transgenic Mice Differentially Affects Atherogenesis and Established Plaques
Open accessAbstract
Although monocytes/macrophages are considered important in atherogenesis, their role in established plaques is unclear. For example, macrophage content is associated with plaque instability, but their loss through cell death is observed at sites of plaque rupture. To examine the role of monocytes/macrophages in atherosclerosis, we developed CD11b–diphtheria toxin (DT) receptor (DTR) transgenic mice, whereby administration of DT selectively kills monocytes/macrophages. DT treatment reduced peripheral blood monocytes and tissue macrophages and inhibited macrophage function in CD11b-DTR mice and apolipoprotein E–null (apoE −/− ) mice transplanted with CD11b-DTR bone marrow. In atherogenesis experiments, DT markedly reduced plaque development and altered plaque composition, reducing collagen content and necrotic core formation. In mice with established plaques, acute DT treatment induced macrophage apoptosis and reduced macrophage content but did not induce plaque inflammation, thrombosis, or rupture. Furthermore, despite a 50% reduction in monocytes, chronic DT treatment of these mice did not alter plaque extent or composition, most likely because of ongoing recruitment/proliferation of monocytes with recovery of macrophage content. We conclude that monocytes/macrophages are critical to atherogenesis, but established plaques are more resistant to reductions in monocytes.
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Clodronate treatment does not reduce size of established plaques, suggesting it may be most effective early.
“However, clodronate treatment was not shown to reduce the size of plaques that were already established prior to treatment, suggesting that such a treatment may be most effective in the early stages of disease progression [59].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [59]
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References 25 · Cited by 261
Research works printed but not linked: 6
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- Authors
- Stoneman, V., Braganza, D., Figg, N., Mercer, J., Lang, R., Goddard, M., & Bennett, M.
- Affiliations
- University of Cambridge (GB)
- Venue
- Circulation Research
- Published
- 2007-03-30
- Volume
- 100
- Issue
- 6
- Pages
- 884-893
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC2040259
- OpenAlex
- W2164159495
- Cited by
- 261
- References
- 25
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 6 · 2022: 8 · 2021: 10 · 2020: 7 · 2019: 17 · 2018: 12 · 2017: 16 · 2016: 22 · 2015: 9 · 2014: 20 · 2013: 23 · 2012: 23
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- British Heart Foundation (RG/04/001/16468)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Keywords
- monocytes, macrophages, atherogenesis, diphtheria toxin receptor, CD11b, macrophage apoptosis, plaque composition, necrotic core, plaque vulnerability, plaque rupture, apolipoprotein E-null mice, bone marrow transplantation, plaque inflammation
- MeSH terms
- Animals, Aorta, Apolipoproteins E, Cell Count, Cells, Cultured, Diphtheria Toxin, Humans, Macrophages, Mice, Transgenic, Monocytes, Organ Specificity, Promoter Regions, Genetic, Receptors, Cell Surface, Recombinant Fusion Proteins, Bone Marrow Transplantation, Mice, Knockout, Disease Progression, Intercellular Signaling Peptides and Proteins, CD11b Antigen, Green Fluorescent Proteins, Atherosclerosis, Mice, Heparin-binding EGF-like Growth Factor
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