Modulation of atherosclerosis in mice by Toll-like receptor 2
Open accessAbstract
Epidemiologic evidence has established a relationship between microbial infection and atherosclerosis. Mammalian TLRs provide clues on the mechanism of this inflammatory cascade. TLR2 has a large ligand repertoire that includes bacterial-derived exogenous and possibly host-derived endogenous ligands. In atherosclerosis-susceptible low-density lipoprotein receptor-deficient (Ldlr-/-) mice, complete deficiency of TLR2 led to a reduction in atherosclerosis. However, with BM transplantation, loss of TLR2 expression from BM-derived cells had no effect on disease progression. This suggested that an unknown endogenous TLR2 agonist influenced lesion progression by activating TLR2 in cells that were not of BM cell origin. Moreover, with intraperitoneal administration of a synthetic TLR2/TLR1 agonist, Pam3CSK4, disease burden was dramatically increased in Ldlr-/- mice. A complete deficiency of TLR2 in Ldlr-/- mice, as well as a deficiency of TLR2 only in BM-derived cells in Ldlr-/- mice, led to striking protection against Pam3CSK4-mediated atherosclerosis, suggesting a role for BM-derived cell expression of TLR2 in transducing the effects of an exogenous TLR2 agonist. These studies support the concept that chronic or recurrent microbial infections may contribute to atherosclerotic disease. Additionally, these data suggest the presence of host-derived endogenous TLR2 agonists.
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Deficiency in either TLR2 or TLR4 signalling reduced atherosclerotic disease in mouse models.
“Deficiency in either TLR2 or TLR4 signalling also reduced atherosclerotic disease in mouse models35–37, and TLR4, specifically, has been shown to mediate inflammatory responses to free fatty acids,”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [35]
TLR signalling is implicated in the pathogenesis of atherosclerotic disease.
“TLR signalling is also implicated in the pathogenesis of atherosclerotic disease35–37.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [35]
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- Authors
- Mullick, A. E.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Mullick, A. E.
- ORCID
- Mullick, A. E.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-11-01
- Volume
- 115
- Issue
- 11
- Pages
- 3149-3156
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1242192
- OpenAlex
- W1978369960
- Cited by
- 549
- References
- 43
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 14 · 2023: 11 · 2022: 18 · 2021: 11 · 2020: 29 · 2019: 22 · 2018: 20 · 2017: 24 · 2016: 20 · 2015: 25 · 2014: 29 · 2013: 39 · 2012: 42
- FWCI
- 10.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tobacco-Related Disease Research Program
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL035297, HL007195, HL 035297, T32HL007195)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- atherosclerosis, TLR2, Ldlr-deficient mice, bone marrow-derived cells, Pam3CSK4, microbial infection, inflammation, atherosclerotic plaque progression, TLR1
- MeSH terms
- Animals, Aorta, Bone Marrow Cells, Cholesterol, Lipoproteins, Male, Mice, Inbred C57BL, Receptors, LDL, Severity of Illness Index, Bone Marrow Transplantation, Mice, Knockout, Atherosclerosis, Toll-Like Receptor 2, Mice
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