The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands
Open accessAbstract
Reciprocity of inflammation, oxidative stress and neovascularization is emerging as an important mechanism underlying numerous processes from tissue healing and remodelling to cancer progression. Whereas the mechanism of hypoxia-driven angiogenesis is well understood, the link between inflammation-induced oxidation and de novo blood vessel growth remains obscure. Here we show that the end products of lipid oxidation, ω-(2-carboxyethyl)pyrrole (CEP) and other related pyrroles, are generated during inflammation and wound healing and accumulate at high levels in ageing tissues in mice and in highly vascularized tumours in both murine and human melanoma. The molecular patterns of carboxyalkylpyrroles are recognized by Toll-like receptor 2 (TLR2), but not TLR4 or scavenger receptors on endothelial cells, leading to an angiogenic response that is independent of vascular endothelial growth factor. CEP promoted angiogenesis in hindlimb ischaemia and wound healing models through MyD88-dependent TLR2 signalling. Neutralization of endogenous carboxyalkylpyrroles impaired wound healing and tissue revascularization and diminished tumour angiogenesis. Both TLR2 and MyD88 are required for CEP-induced stimulation of Rac1 and endothelial migration. Taken together, these findings establish a new function of TLR2 as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Coussens, L. M., & Werb, Z. (2002) · Nature · doi:10.1038/nature01322 · Cited by 15,111
Wound Healing--Aiming for Perfect Skin Regeneration
Martin, P. (1997) · Science · doi:10.1126/science.276.5309.75 · Cited by 4,804
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690
Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A., Mignot, G., Maiuri, M. C., Ullrich, E., Saulnier, P., et al. (2007) · Nature Medicine · doi:10.1038/nm1622 · Cited by 3,056
Ozinsky, A., Underhill, D. M., Fontenot, J. D., Hajjar, A. M., Smith, K. D., Wilson, C. B., Schroeder, L., & Aderem, A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.250476497 · Cited by 2,085
Segal, A. W. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115653 · Cited by 1,789
A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish
Niethammer, P., Grabher, C., Look, A. T., & Mitchison, T. J. (2009) · Nature · doi:10.1038/nature08119 · Cited by 1,541
Cell Activation and Apoptosis by Bacterial Lipoproteins Through Toll-like Receptor-2
Aliprantis, A. O., Yang, R.-B., Mark, M. R., Suggett, S., Devaux, B., Radolf, J. D., Klimpel, G. R., Godowski, P., & Zychlinsky, A. (1999) · Science · doi:10.1126/science.285.5428.736 · Cited by 1,474
Vogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A. D., Nacken, W., Foell, D., van der Poll, T., Sorg, C., et al. (2007) · Nature Medicine · doi:10.1038/nm1638 · Cited by 1,418
Regulation of lung injury and repair by Toll-like receptors and hyaluronan
Jiang, D., Liang, J., Fan, J., Yu, S., Chen, S., Luo, Y., Prestwich, G. D., Mascarenhas, M. M., Garg, H. G., Quinn, D. A., et al. (2005) · Nature Medicine · doi:10.1038/nm1315 · Cited by 1,401
Drusen proteome analysis: an approach to the etiology of age-related macular degeneration
Crabb, J. W., Miyagi, M., Gu, X., Shadrach, K., West, K. A., Sakaguchi, H., Kamei, M., Hasan, A., Yan, L., Rayborn, M. E., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222551899 · Cited by 1,208
Self-citationInnate Immunity Gone Awry: Linking Microbial Infections to Chronic Inflammation and Cancer
Karin, M., Lawrence, T., & Nizet, V. (2006) · Cell · doi:10.1016/j.cell.2006.02.016 · Cited by 942
Schaefer, L., Babelova, A., Kiss, E., Hausser, H.-J., Baliova, M., Krzyzankova, M., Marsche, G., Young, M. F., Mihalik, D., Götte, M., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23755 · Cited by 850
Mazzone, M., Dettori, D., Leite de Oliveira, R., Loges, S., Schmidt, T., Jonckx, B., Tian, Y.-M., Lanahan, A. A., Pollard, P., Ruiz de Almodovar, C., et al. (2009) · Cell · doi:10.1016/j.cell.2009.01.020 · Cited by 812
Pattern recognition receptors and control of adaptive immunity
Palm, N. W., & Medzhitov, R. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00731.x · Cited by 729
The codependence of angiogenesis and chronic inflammation
Jackson, J. R., Seed, M. P., Kircher, C. H., Willoughby, D. A., & Winkler, J. D. (1997) · The FASEB Journal · doi:10.1096/fasebj.11.6.9194526 · Cited by 694
Toll-like receptor 2–mediated NF-κB activation requires a Rac1-dependent pathway
Arbibe, L., Mira, J.-P., Teusch, N., Kline, L., Guha, M., Mackman, N., Godowski, P. J., Ulevitch, R. J., & Knaus, U. G. (2000) · Nature Immunology · doi:10.1038/82797 · Cited by 664
Pathogen recognition with Toll-like receptors
Kawai, T., & Akira, S. (2005) · Current Opinion in Immunology · doi:10.1016/j.coi.2005.02.007 · Cited by 576
Modulation of atherosclerosis in mice by Toll-like receptor 2
Mullick, A. E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25482 · Cited by 549
Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype
Podrez, E. A., Byzova, T. V., Febbraio, M., Salomon, R. G., Ma, Y., Valiyaveettil, M., Poliakov, E., Sun, M., Finton, P. J., Curtis, B. R., et al. (2007) · Nature Medicine · doi:10.1038/nm1626 · Cited by 513
Self-citationAkt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo
Chen, J., Somanath, P. R., Razorenova, O., Chen, W. S., Hay, N., Bornstein, P., & Byzova, T. V. (2005) · Nature Medicine · doi:10.1038/nm1307 · Cited by 456
Self-citationPodrez, E. A., Poliakov, E., Shen, Z., Zhang, R., Deng, Y., Sun, M., Finton, P. J., Shan, L., Gugiu, B., Fox, P. L., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203318200 · Cited by 449
Self-citationRegulation of Angiogenesis by Oxygen and Metabolism
Fraisl, P., Mazzone, M., Schmidt, T., & Carmeliet, P. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.01.003 · Cited by 413
Zähringer, U., Lindner, B., Inamura, S., Heine, H., & Alexander, C. (2008) · Immunobiology · doi:10.1016/j.imbio.2008.02.005 · Cited by 403
Gu, X., Meer, S. G., Miyagi, M., Rayborn, M. E., Hollyfield, J. G., Crabb, J. W., & Salomon, R. G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305460200 · Cited by 325
Self-citationAn essential role for Rac1 in endothelial cell function and vascular development
Tan, W., Palmby, T. R., Gavard, J., Amornphimoltham, P., Zheng, Y., & Gui, J. S. (2008) · The FASEB Journal · doi:10.1096/fj.07-096438 · Cited by 227
Toll-like Receptor 2 Senses β-Cell Death and Contributes to the Initiation of Autoimmune Diabetes
Kim, H. S., Han, M. S., Chung, K. W., Kim, S., Kim, E., Kim, M. J., Jang, E., Lee, H. A., Youn, J., Akira, S., et al. (2007) · Immunity · doi:10.1016/j.immuni.2007.06.010 · Cited by 195
Ebrahem, Q., Renganathan, K., Sears, J., Vasanji, A., Gu, X., Lu, L., Salomon, R. G., Crabb, J. W., & Anand-Apte, B. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601552103 · Cited by 117
Self-citationAnthranilic Acid Amides: A Novel Class of Antiangiogenic VEGF Receptor Kinase Inhibitors
Manley, P. W., Furet, P., Bold, G., et al. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020899q · Cited by 103
Grote, K., Schuett, H., Salguero, G., Grothusen, C., Jagielska, J., Drexler, H., Mühlradt, P. F., & Schieffer, B. (2010) · Blood · doi:10.1182/blood-2009-05-224402 · Cited by 81
The angiogenic response is dictated by β3 integrin on bone marrow–derived cells
Feng, W., McCabe, N. P., Mahabeleshwar, G. H., Somanath, P. R., Phillips, D. R., & Byzova, T. V. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200802179 · Cited by 48
Self-citationMethods for Isolation of Endothelial and Smooth Muscle Cells and In Vitro Proliferation Assays
Mahabeleshwar, G. H., Somanath, P. R., & Byzova, T. V. (2006) · Humana Press eBooks · doi:10.1385/1-59745-213-0:197 · Cited by 37
Self-citation
Cited by
Toll-Like Receptor Signaling Pathways
Kawasaki, T., & Kawai, T. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00461 · Cited by 3,233
The immune system in atherosclerosis
Hansson, G. K., & Hermansson, A. (2011) · Nature Immunology · doi:10.1038/ni.2001 · Cited by 2,317
Microenvironmental regulation of tumour angiogenesis
De Palma, M., Biziato, D., & Petrova, T. V. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.51 · Cited by 1,847
The role of ROS in tumour development and progression
Cheung, E. C., & Vousden, K. H. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-021-00435-0 · Cited by 1,595
Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis
Förstermann, U., Xia, N., & Li, H. (2017) · Circulation Research · doi:10.1161/circresaha.116.309326 · Cited by 1,519
Metadata
- Authors
- West, X. Z., Malinin, N. L., Merkulova, A. A., Tischenko, M., Kerr, B. A., Borden, E. C., Podrez, E. A., Salomon, R. G., & Byzova, T. V.
- Venue
- Nature
- Published
- 2010-10
- Volume
- 467
- Issue
- 7318
- Pages
- 972-976
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2009592273
- Cited by
- 431
- References
- 32
- FWCI
- 15.22
- Type
- journal article
- Language
- en
- Open access
- green
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
