The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E
Open accessAbstract
Toll-like receptors (TLRs) and the downstream adaptor molecule myeloid differentiation factor 88 (MyD88) play an essential role in the innate immune responses. Here, we demonstrate that genetic deficiency of TLR4 or MyD88 is associated with a significant reduction of aortic plaque areas in atherosclerosis-prone apolipoprotein E-deficient mice, despite persistent hypercholesterolemia, implying an important role for the innate immune system in atherogenesis. Apolipoprotein E-deficient mice that also lacked TLR4 or MyD88 demonstrated reduced aortic atherosclerosis that was associated with reductions in circulating levels of proinflammatory cytokines IL-12 or monocyte chemoattractant protein 1, plaque lipid content, numbers of macrophage, and cyclooxygenase 2 immunoreactivity in their plaques. Endothelial-leukocyte adhesion in response to minimally modified low-density lipoprotein was reduced in aortic endothelial cells derived from MyD88-deficient mice. Taken together, our results suggest an important role for TLR4 and MyD88 signaling in atherosclerosis in a hypercholesterolemic mouse model, providing a pathophysiologic link between innate immunity, inflammation, and atherogenesis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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 [36]
In the citing paper
“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 [36]
Citations
Cites
Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725
Inflammation in atherosclerosis
Libby, P. (2002) · Nature · doi:10.1038/nature01323 · Cited by 8,315
Inflammation and Atherosclerosis
Libby, P., Ridker, P. M., & Maseri, A. (2002) · Circulation · doi:10.1161/hc0902.104353 · Cited by 7,724
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129
CD14, a Receptor for Complexes of Lipopolysaccharide (LPS) and LPS Binding Protein
Wright, S. D., Ramos, R., Tobias, P. S., Ulevitch, R. J., & Mathison, J. C. (1990) · Science · doi:10.1126/science.1698311 · Cited by 3,996
Glass, C. K., & Witztum, J. L. (2001) · Cell · doi:10.1016/s0092-8674(01)00238-0 · Cited by 3,094
TLR4 mutations are associated with endotoxin hyporesponsiveness in humans
Arbour, N. C., Lorenz, E., Schutte, B. C., Zabner, J., Kline, J. N., Jones, M., Frees, K., Watt, J. L., & Schwartz, D. A. (2000) · Nature Genetics · doi:10.1038/76048 · Cited by 2,024
Boring, L., Gosling, J., Cleary, M., & Charo, I. F. (1998) · Nature · doi:10.1038/29788 · Cited by 1,965
Gu, L., Okada, Y., Clinton, S. K., Gerard, C. J., Sukhova, G. K., Libby, P., & Rollins, B. J. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80139-2 · Cited by 1,574
Research works printed but not linked: 1
- Ameziane, N., Beillat, T., Verpillat, P., Chollet-Martin, S., Aumont, M. C., Seknadji, P., Lamotte, M., Lebret, D., Ollivier, V. & De Prost, D. (2003) Arterioscler. Thromb. Vasc. Biol. 23, 61–64.
Cited by
Sorted by citations
Toll-like receptors in innate immunity
Takeda, K. (2004) · International Immunology · doi:10.1093/intimm/dxh186 · Cited by 3,328
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051
Macrophages in atherosclerosis: a dynamic balance
Moore, K. J., Sheedy, F. J., & Fisher, E. A. (2013) · Nature reviews. Immunology · doi:10.1038/nri3520 · Cited by 2,559
The immune system in atherosclerosis
Hansson, G. K., & Hermansson, A. (2011) · Nature Immunology · doi:10.1038/ni.2001 · Cited by 2,389
The immune response in atherosclerosis: a double-edged sword
Hansson, G. K., & Libby, P. (2006) · Nature reviews. Immunology · doi:10.1038/nri1882 · Cited by 2,220
Metadata
- Authors
- Michelsen, K. S., Wong, M. H., Shah, P. K., Zhang, W., Yano, J., Doherty, T. M., Akira, S., Rajavashisth, T. B., & Arditi, M.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Arditi, Moshe
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-07-12
- Volume
- 101
- Issue
- 29
- Pages
- 10679-10684
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC489994
- OpenAlex
- W2018788678
- Cited by
- 1,019
- References
- 57
- Citations by year
- 2026: 20 · 2025: 17 · 2024: 25 · 2023: 25 · 2022: 35 · 2021: 21 · 2020: 36 · 2019: 52 · 2018: 36 · 2017: 37 · 2016: 43 · 2015: 64 · 2014: 53 · 2013: 68 · 2012: 68
- FWCI
- 18.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl058555-04)
- National Heart, Lung, and Blood Institute (HL66436, HL 58555, R01HL066436, R29HL051980, HL 51980, R01HL051980)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- TLR4, MyD88, atherosclerosis, apolipoprotein E deficiency, innate immunity, atherogenesis, aortic plaque, hypercholesterolemia, inflammatory cytokines, IL-12, MCP-1, macrophages, cyclooxygenase-2, plaque inflammation
- MeSH terms
- Animals, Antigens, Differentiation, Aorta, Apolipoproteins E, Arteriosclerosis, Cells, Cultured, Female, Humans, Immunity, Innate, Isoenzymes, Lipids, Macrophages, Male, Membrane Glycoproteins, Membrane Proteins, Mice, Inbred C57BL, Phenotype, Prostaglandin-Endoperoxide Synthases, Receptors, Cell Surface, Receptors, Immunologic, Signal Transduction, Mice, Knockout, Interleukin-12, Chemokine CCL2, Endothelial Cells, Adaptor Proteins, Signal Transducing, Lipid Metabolism, Toll-Like Receptors, Toll-Like Receptor 4, Mice, Cyclooxygenase 2, Myeloid Differentiation Factor 88
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
