Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury

doi:10.1038/s41467-017-02401-7

CORC > 化学研究所 > 中国科学院化学研究所

	Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury
	Li, Tuoyi 1,2,3; Yu, Bing 1,2; Liu, Zhixin 4,5; Li, Jingyuan 6; Ma, Mingliang 4,5,7; Wang, Yingbao 1,2,7; Zhu, Mingjiang ; Yin, Huiyong ; Wang, Xiaofeng 6; Fu, Yi 1,2
刊名	NATURE COMMUNICATIONS
	2018-01-02
卷号	9
ISSN号	2041-1723
DOI	10.1038/s41467-017-02401-7
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.
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000419306000002
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/45369]
专题	中国科学院化学研究所
通讯作者	Sun, Jinpeng; Kong, Wei
作者单位	1.Peking Univ, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100191, Peoples R China 2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China 3.Capital Normal Univ, High Sch, Beijing 100048, Peoples R China 4.Shandong Univ, Sch Med, Dept Biochem & Mol Biol, Jinan 250012, Shandong, Peoples R China 5.Minist Educ, Key Lab Expt Teratol, Jinan 250012, Shandong, Peoples R China 6.Inst High Energy Phys, CAS Key Lab Biol Effects Nanomat & Nanosafety, 19 B,Yuquan Rd, Beijing 100049, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Biol Sci, INS, Key Lab Food Safety Res, Shanghai 200031, Peoples R China 8.Chinese Acad Sci, Key Lab Mol Nanostruct & Nanotechnol, Inst Chem, CAS Res Educ Ctr Excellence Mol Sci, Beijing 100190, Peoples R China 9.Duke Univ, Sch Med, Med Ctr, Durham, NC 27710 USA
推荐引用方式 GB/T 7714	Li, Tuoyi,Yu, Bing,Liu, Zhixin,et al. Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury[J]. NATURE COMMUNICATIONS,2018,9.
APA	Li, Tuoyi.,Yu, Bing.,Liu, Zhixin.,Li, Jingyuan.,Ma, Mingliang.,...&Kong, Wei.(2018).Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury.NATURE COMMUNICATIONS,9.
MLA	Li, Tuoyi,et al."Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury".NATURE COMMUNICATIONS 9(2018).