The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Phagocytosis of Apoptotic Cells by Macrophages Is Impaired in Atherosclerosis
Abstract
OBJECTIVE: Apoptotic cell death has been demonstrated in advanced human atherosclerotic plaques. Apoptotic cells (ACs) should be rapidly removed by macrophages, otherwise secondary necrosis occurs, which in turn elicits inflammatory responses and plaque progression. Therefore, we investigated the efficiency of phagocytosis of ACs by macrophages in atherosclerosis. METHODS AND RESULTS: Human endarterectomy specimens and human tonsils were costained for CD68 (macrophages) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) (apoptosis). Free and phagocytized ACs were counted in both tissues. The ratio of free versus phagocytized AC was 19-times higher in human atherosclerotic plaques as compared with human tonsils, indicating a severe defect in clearance of AC. Impaired phagocytosis of AC was also detected in plaques from cholesterol-fed rabbits and did not further change with plaque progression. In vitro experiments with J774 or peritoneal mouse macrophages showed that several factors caused impaired phagocytosis of AC including cytoplasmic overload of macrophages with indigestible material (beads), free radical attack, and competitive inhibition among oxidized red blood cells, oxidized low-density lipoprotein and ACs for the same receptor(s) on the macrophage. CONCLUSIONS: Our data demonstrate that phagocytosis of ACs is impaired in atherosclerotic plaques, which is at least partly attributed to oxidative stress and cytoplasmic saturation with indigestible material.
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“The impaired ability of macrophage efferocytosis would enhance atherogenesis [139,140,141] and atherosclerotic plaque instability [142,143,144].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [140]
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Mechanisms of phagocytosis in macrophages
Aderem, A., & Underhill, D. M. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.593 · Cited by 2,854
Fitzgerald, M., Hayward, I. P., Thomas, A. C., Campbell, J. H., & CAMPBELL, G. R. (1995) · Cited by 2,552
Oxidative Stress and Vascular Disease
Madamanchi, N. R., Vendrov, A., & Runge, M. S. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000150649.39934.13 · Cited by 1,618
Corpse clearance defines the meaning of cell death
Savill, J., & Fadok, V. A. (2000) · Nature · doi:10.1038/35037722 · Cited by 1,572
Shed Membrane Microparticles With Procoagulant Potential in Human Atherosclerotic Plaques
Mallat, Z., Hugel, B., Ohan, J., Lesèche, G., Freyssinet, J., & Tedgui, A. (1999) · Circulation · doi:10.1161/01.cir.99.3.348 · Cited by 636
Phagocyte receptors for apoptotic cells: recognition, uptake, and consequences
Fadok, V. A., Bratton, D. L., & Henson, P. M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14122 · Cited by 474
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Elevated Levels of Oxidative DNA Damage and DNA Repair Enzymes in Human Atherosclerotic Plaques
Martinet, W., Knaapen, M., Meyer, G. R. Y. D., Herman, A. G., & Kockx, M. M. (2002) · Circulation · doi:10.1161/01.cir.0000026393.47805.21 · Cited by 448
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Macrophages in the Pathogenesis of Atherosclerosis
Moore, K. J., & Tabas, I. (2011) · Cell · doi:10.1016/j.cell.2011.04.005 · Cited by 2,669
Mechanisms of plaque formation and rupture
Bentzon, J. F., Otsuka, F., Virmani, R., & Falk, E. (2014) · Circulation Research · doi:10.1161/circresaha.114.302721 · Cited by 2,391
Vascular smooth muscle cells in atherosclerosis
Bennett, M. R., Sinha, S., & Owens, G. K. (2016) · Circulation Research · doi:10.1161/circresaha.115.306361 · Cited by 2,179
Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways
Tedgui, A., & Mallat, Z. (2006) · Physiological Reviews · doi:10.1152/physrev.00024.2005 · Cited by 1,751
Role of cholesterol and lipid organization in disease
Maxfield, F. R., & Tabas, I. A. (2005) · Nature · doi:10.1038/nature04399 · Cited by 1,331
Metadata
- Authors
- Schrijvers, D. M., De Meyer, G. R. Y., Kockx, M. M., Herman, A. G., & Martinet, W.
- Affiliations
- University of Antwerp (BE)
- From the Division of Pharmacology (D.M.S., G.R.Y.D.M., M.M.K., A.G.H., W.M.), University of Antwerp, Wilrijk, Belgium; and the Department of Pathology (M.M.K.), AZ Middelheim, Antwerp, Belgium
- Venue
- Arteriosclerosis Thrombosis and Vascular Biology
- Published
- 2005-06
- Volume
- 25
- Issue
- 6
- Pages
- 1256-1261
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2163327518
- Cited by
- 509
- References
- 42
- Citations by year
- 2026: 13 · 2025: 32 · 2024: 34 · 2023: 31 · 2022: 34 · 2021: 33 · 2020: 21 · 2019: 24 · 2018: 29 · 2017: 32 · 2016: 20 · 2015: 25 · 2014: 21 · 2013: 24 · 2012: 16
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- phagocytosis of apoptotic cells, macrophages, atherosclerosis, atherosclerotic plaque, secondary necrosis, oxidative stress, oxidized LDL, plaque progression, cholesterol-fed rabbits, tonsil
- MeSH terms
- Aged, Animals, Carotid Artery Diseases, Cytoplasm, Erythrocytes, Female, Humans, Lipoproteins, LDL, Male, Necrosis, Phagocytosis, Rabbits, Palatine Tonsil, Apoptosis, Macrophages, Peritoneal, Oxidative Stress, U937 Cells, Mice
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