Decreased atherosclerosis in CX3CR1–/– mice reveals a role for fractalkine in atherogenesis
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The hallmark of early atherosclerosis is the accumulation of lipid-laden macrophages in the subendothelial space. Circulating monocytes are the precursors of these "foam cells," and recent evidence suggests that chemokines play important roles in directing monocyte migration from the blood to the vessel wall. Fractalkine (FK) is a structurally unusual chemokine that can act either as a soluble chemotactic factor or as a transmembrane-anchored adhesion receptor for circulating leukocytes. A polymorphism in the FK receptor, CX(3)CR1, has been linked to a decrease in the incidence of coronary artery disease. To determine whether FK is critically involved in atherogenesis, we deleted the gene for CX(3)CR1 and crossed these mice into the apoE(-/-) background. Here we report that FK is robustly expressed in lesional smooth muscle cells, but not macrophages, in apoE(-/-) mice on a high-fat diet. CX(3)CR1(-/-) mice have a significant reduction in macrophage recruitment to the vessel wall and decreased atherosclerotic lesion formation. Taken together, these data provide strong evidence that FK plays a key role in atherogenesis.
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CX3CR1 and its ligand fractalkine have been implicated in recruitment of mononuclear phagocytes to sites of inflammation and injury and play roles in the pathogenesis of several inflammatory conditions including atherosclerosis, neuropathic pain, and asthma.
“CX3CR1 and its chemokine ligand fractalkine (CX3CL1) have been implicated in the recruitment of mononuclear phagocytes to sites of inflammation and injury (7, 10, 11) and play roles in the pathogenesis of several inflammatory conditions, including atherosclerosis (12, 13), neuropathic pain (14), and asthma (15).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [13]
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Self-citation
- Authors
- Lesnik, P., Haskell, C. A., & Charo, I. F.
- Affiliations
- Gladstone Institutes (US)
- Corresponding author
- Charo, Israel F.
- ORCID
- Lesnik, Philippe
- Venue
- Journal of Clinical Investigation
- Published
- 2003-02-01
- Volume
- 111
- Issue
- 3
- Pages
- 333-340
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC151849
- OpenAlex
- W2156098329
- Cited by
- 487
- References
- 3
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 8 · 2023: 13 · 2022: 12 · 2021: 9 · 2020: 14 · 2019: 10 · 2018: 15 · 2017: 17 · 2016: 13 · 2015: 20 · 2014: 24 · 2013: 16 · 2012: 30
- FWCI
- 12.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL-52773)
- National Heart, Lung, and Blood Institute (R01HL063894, R01HL052773, HL 52773, HL63894)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- fractalkine, CX3CR1, atherosclerosis, atherogenesis, monocyte recruitment, foam cells, macrophage recruitment, chemokines, smooth muscle cells, ApoE-deficient mice, high-fat diet, coronary artery disease
- MeSH terms
- CX3C Chemokine Receptor 1, Animals, Animal Feed, Aorta, Arteriosclerosis, Cell Movement, Coronary Artery Disease, Dietary Fats, Foam Cells, Genotype, Membrane Proteins, Monocytes, Polymorphism, Genetic, RNA, Messenger, Time Factors, Receptors, Chemokine, Reverse Transcriptase Polymerase Chain Reaction, Chemokines, CX3C, CD11b Antigen, Mice, Chemokine CX3CL1
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