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.
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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
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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
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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
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- 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. (2010). Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands. Nature. https://doi.org/10.1038/nature09421
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