Alternative macrophages in atherosclerosis: not always protective!
Open accessAbstract
Atherosclerosis is a chronic inflammatory disease of the vasculature that is initiated by cholesterol deposition into the arterial wall, which triggers the infiltration of immune and inflammatory cells, including monocytes and macrophages. As atherosclerotic plaques progress, localized hypoxia promotes compensatory angiogenesis from the vasa vasorum. Immature neovessels are prone to leakage, thus destabilizing the plaque and leading to intraplaque hemorrhage. Macrophages with different phenotypes, ranging from classical inflammatory subtypes to alternatively activated antiinflammatory macrophages, have been identified in atherosclerotic lesions. Antiinflammatory hemoglobin-scavenging CD163+ macrophages are present in neovessel- and hemorrhage-rich areas; however, the role of these macrophages in atherogenesis has been unclear. In this issue of the JCI, Guo, Akahori, and colleagues show that CD163+ macrophages promote angiogenesis, vessel permeability, and leucocyte infiltration in human and mouse atherosclerotic lesions through a mechanism involving hemoglobin:haptoglobin/CD163/HIF1α-mediated VEGF induction. This study thus identifies proatherogenic properties of CD163+ macrophages, which previously were thought to be beneficial.
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ApoE-mediated macrophage uptake of VLDL and remnants promotes an inflammatory (M1) phenotype, enhances inflammation, increases phagocytosis and foam cell formation, exerts defective efferocytotic activity, and favours fibrous cap thinning due to activation of metalloprotease expression.
“ApoE-mediated macrophage uptake of VLDL and remnants promotes an inflammatory (M1) phenotype,2,17,139 enhances inflammation, increases phagocytosis and foam cell formation, exerts defective efferocytotic activity, and favours fibrous cap thinning due to activation of metalloprotease expression140”
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- Authors
- Pourcet, B., & Staels, B.
- Affiliations
- Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (FR)
- Corresponding author
- Staels, Bart
- ORCID
- Staels, Bart
- Venue
- Journal of Clinical Investigation
- Published
- 2018-02-19
- Volume
- 128
- Issue
- 3
- Pages
- 910-912
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5824921
- OpenAlex
- W2788668307
- Cited by
- 62
- References
- 16
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 14 · 2021: 8 · 2020: 10 · 2019: 3 · 2018: 1
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-16-CE14-0001)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- atherosclerosis, CD163+ macrophages, alternative macrophage activation, haptoglobin, HIF-1α, vascular endothelial growth factor, angiogenesis, intraplaque hemorrhage, vasa vasorum, vascular permeability, leukocyte infiltration
- MeSH terms
- Animals, Capillary Permeability, Humans, Inflammation, Macrophages, Atherosclerosis, Mice, Plaque, Atherosclerotic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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