The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury
Open accessAbstract
Hyperhomocysteinemia (HHcy) is a risk factor for various cardiovascular diseases. However, the mechanism underlying HHcy-aggravated vascular injury remains unclear. Here we show that the aggravation of abdominal aortic aneurysm by HHcy is abolished in mice with genetic deletion of the angiotensin II type 1 (AT1) receptor and in mice treated with an AT1 blocker. We find that homocysteine directly activates AT1 receptor signalling. Homocysteine displaces angiotensin II and limits its binding to AT1 receptor. Bioluminescence resonance energy transfer analysis reveals distinct conformational changes of AT1 receptor upon binding to angiotensin II and homocysteine. Molecular dynamics and site-directed mutagenesis experiments suggest that homocysteine regulates the conformation of the AT1 receptor both orthosterically and allosterically by forming a salt bridge and a disulfide bond with its Arg 167 and Cys 289 residues, respectively. Together, these findings suggest that strategies aimed at blocking the AT1 receptor may mitigate HHcy-associated aneurysmal vascular injuries.
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Scalable molecular dynamics with NAMD
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Fu, T.-M., & Tian, H. (2019) · Current Pollution Reports · doi:10.1007/s40726-019-00115-6 · Cited by 138
Lu, H., Sun, J., Liang, W., Chang, Z., Rom, O., Zhao, Y., Zhao, G., Xiong, W., Wang, H., Zhu, T., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.044803 · Cited by 98
Self-citation
Metadata
- Authors
- Li, T., Yu, B., Liu, Z., Li, J., Ma, M., Wang, Y., Zhu, M., Yin, H., Wang, X., Fu, Y., Yu, F., Wang, X., Fang, X., Sun, J., & Kong, W.
- Venue
- Nature Communications
- Published
- 2018-01-02
- Volume
- 9
- Issue
- 1
- Pages
- 11-11
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2780027234
- Cited by
- 258
- References
- 48
- FWCI
- 16.49
- Type
- journal article
- Language
- en
- Open access
- gold
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- Li, T., Yu, B., Liu, Z., Li, J., Ma, M., Wang, Y., Zhu, M., Yin, H., Wang, X., Fu, Y., Yu, F., Wang, X., Fang, X., Sun, J., & Kong, W. (2018). Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury. Nature Communications. https://doi.org/10.1038/s41467-017-02401-7
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