Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury
文献类型：期刊论文
| 作者 | Yin, HY; Li, TY; Yu, B; Liu, ZX; Li, JY ; Ma, ML; Wang, YB; Zhu, MJ; Wang, XF; Fu, Y
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| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2018 |
| 卷号 | 9页码:11 |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/s41467-017-02401-7 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| WOS关键词 | ABDOMINAL AORTIC-ANEURYSM ; SMOOTH-MUSCLE-CELLS ; INDEPENDENT RISK-FACTOR ; G-PROTEIN ; MYOCARDIAL-INFARCTION ; ENDOTHELIAL-CELLS ; BLOOD-PRESSURE ; MICE ; HYPERHOMOCYSTEINEMIA ; INHIBITION |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000419306000002 |
| 源URL | [http://ir.ihep.ac.cn/handle/311005/285520]  |
| 专题 | 高能物理研究所_多学科研究中心 中国科学院高能物理研究所_中国散裂中子源 |
| 作者单位 | 中国科学院高能物理研究所 |
| 推荐引用方式 GB/T 7714 | Yin, HY,Li, TY,Yu, B,et al. Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury[J]. NATURE COMMUNICATIONS,2018,9:11. |
| APA | Yin, HY.,Li, TY.,Yu, B.,Liu, ZX.,Li, JY.,...&王晓峰.(2018).Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury.NATURE COMMUNICATIONS,9,11. |
| MLA | Yin, HY,et al."Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury".NATURE COMMUNICATIONS 9(2018):11. |
入库方式： OAI收割
来源：高能物理研究所
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