The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques
Open accessAbstract
Atherosclerotic plaque formation is fueled by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, thereby establishing chronic inflammation, remain unknown. Here we found that netrin-1, a neuroimmune guidance cue, was secreted by macrophages in human and mouse atheroma, where it inactivated the migration of macrophages toward chemokines linked to their egress from plaques. Acting via its receptor, UNC5b, netrin-1 inhibited the migration of macrophages directed by the chemokines CCL2 and CCL19, activation of the actin-remodeling GTPase Rac1 and actin polymerization. Targeted deletion of netrin-1 in macrophages resulted in much less atherosclerosis in mice deficient in the receptor for low-density lipoprotein and promoted the emigration of macrophages from plaques. Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation.
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“Three mechanisms are available for cholesterol removal from the atherosclerotic plaque (FIG. 3).”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [138]
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Metadata
- Authors
- van Gils, J. M., Derby, M. C., Fernandes, L. R., Ramkhelawon, B., Ray, T. D., Rayner, K. J., Parathath, S., Distel, E., Feig, J. L., Alvarez-Leite, J. I., Rayner, A. J., McDonald, T. O., O'Brien, K. D., Stuart, L. M., Fisher, E. A., Lacy-Hulbert, A., & Moore, K. J.
- Affiliations
- Harvard University (US)
- Universidade Federal de Minas Gerais (BR)
- New York University (US)
- University of Washington (US)
- Corresponding author
- Moore, Kathryn J
- ORCID
- Venue
- Nature Immunology
- Published
- 2012-01-08
- Volume
- 13
- Issue
- 2
- Pages
- 136-143
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3262880
- OpenAlex
- W2044161694
- Cited by
- 365
- References
- 45
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 30 · 2023: 13 · 2022: 29 · 2021: 28 · 2020: 29 · 2019: 23 · 2018: 21 · 2017: 23 · 2016: 32 · 2015: 30 · 2014: 27 · 2013: 30 · 2012: 17
- FWCI
- 14.48
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- American Heart Association
- Heart and Stroke Foundation of Canada
- Massachusetts General Hospital
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Institutes of Health
- Genentech
- National Heart, Lung, and Blood Institute (R01HL084312, P01HL092969, RC1HL100815)
- National Institute of Allergy and Infectious Diseases (R01AI079198, U01AI073871)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cerebrovascular and Carotid Artery Diseases
- Keywords
- netrin-1, atherosclerosis, atherosclerotic plaque, MCP-1, CCL19, Rac1, actin polymerization, chronic inflammation, lipid-laden macrophages, LDL receptor
- MeSH terms
- Netrin Receptors, Netrin-1, Actins, Animals, Cell Movement, Cells, Cultured, Chimera, Humans, Macrophages, Nerve Growth Factors, Neuropeptides, Receptors, Cell Surface, Gene Deletion, Chemokine CCL2, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, Tumor Suppressor Proteins, Atherosclerosis, Mice, Chemokine CCL19, Polymerization, Plaque, Atherosclerotic
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