Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis
Abstract
Chemokines are proinflammatory cytokines that function in leukocyte chemoattraction and activation and have recently been shown to block the HIV-1 infection of target cells through interactions with chemokine receptors. In addition to their function in viral disease, chemokines have been implicated in the pathogenesis of atherosclerosis. Expression of the CC chemokine monocyte chemoattractant protein-1 (MCP-1) is upregulated in human atherosclerotic plaques, in arteries of primates on a hypercholesterolaemic diet; and in vascular endothelial and smooth muscle cells exposed to minimally modified lipids. To determine whether MCP-1 is causally related to the development of atherosclerosis, we generated mice that lack CCR2, the receptor for MCP-1 (ref. 7), and crossed them with apolipoprotein (apo) E-null mice which develop severe atherosclerosis. Here we show that the selective absence of CCR2 decreases lesion formation markedly in apoE-/- mice but has no effect on plasma lipid or lipoprotein concentrations. These data reveal a role for MCP-1 in the development of early atherosclerotic lesions and suggest that upregulation of this chemokine by minimally oxidized lipids is an important link between hyperlipidaemia and fatty streak formation.
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In atherosclerosis, circulating monocytes are recruited to fatty deposits in vascular intima/subintima via CCR2 and endothelial adhesion mechanisms.
“Briefly, in atherosclerosis, circulating monocytes are recruited to sites of fatty deposit accumulation within the vascular intima and subintima via CCR2 and endothelial adhesion mediated mechanisms [49–52].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [51]
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- Authors
- Boring, L., Gosling, J., Cleary, M., & Charo, I. F.
- Affiliations
- Gladstone Institutes (US)
- ORCID
- Cleary, Michael
- Venue
- Nature
- Published
- 1998-08
- Volume
- 394
- Issue
- 6696
- Pages
- 894-897
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1516434930
- Cited by
- 1,965
- References
- 2
- Citations by year
- 2026: 23 · 2025: 36 · 2024: 36 · 2023: 24 · 2022: 40 · 2021: 44 · 2020: 45 · 2019: 46 · 2018: 42 · 2017: 55 · 2016: 53 · 2015: 72 · 2014: 58 · 2013: 62 · 2012: 82
- FWCI
- 27.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Gladstone Institutes
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- atherosclerosis, CCR2, chemokines, MCP-1, CCR2-deficient mice, apolipoprotein E-null mice, atherosclerotic lesion formation, fatty streaks, oxidized lipids, hyperlipidemia, chemokine receptors, leukocyte recruitment
- MeSH terms
- Animals, Aorta, Apolipoproteins E, Arteriosclerosis, Cholesterol, Diet, Atherogenic, Lipoproteins, Mice, Inbred C57BL, Myocardium, Triglycerides, Receptors, Cytokine, Chemokine CCL2, Receptors, Chemokine, Mice, Receptors, CCR2
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