中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海营养与健康研究所
  3. 中国科学院上海生命科学研究院营养科学研究所
Deficiency of Complement C3a and C5a Receptors Prevents Angiotensin II-Induced Hypertension via Regulatory T Cells

文献类型：期刊论文

作者Chen, Xiao-Hui1,2,3,4; Ruan, Cheng-Chao1,2,3,4; Ge, Qian2,4; Ma, Yu2,4; Xu, Jian-Zhong2,4; Chen, Dong-Rui2,4; Zhu, Ding-Liang2,4; Gao, Ping-Jin1,2,3,4; Zhang, Ze-Bei1,3; Lin, Jing-Rong1,3
刊名CIRCULATION RESEARCH
出版日期2018
卷号122期号:7页码:970-983
关键词hypertension immunology inflammation regulatory T cell renin-angiotensin system complement
ISSN号0009-7330
DOI10.1161/CIRCRESAHA.117.312153
文献子类Article
英文摘要Rationale: Inflammation and immunity play crucial roles in the development of hypertension. Complement activation-mediated innate immune response is involved in the regulation of hypertension and target-organ damage. However, whether complement-mediated T-cell functions could regulate blood pressure elevation in hypertension is still unclear. Objective: We aim to determine whether C3aR (complement component 3a receptor) and C5aR (complement component 5a receptor) could regulate blood pressure via modulating regulatory T cells (Tregs). Methods and Results: We showed that angiotensin II (Ang II)-induced hypertension resulted in an elevated expression of C3aR and C5aR in Foxp3 (forkhead box P3)+ Tregs. By using C3aR and C5aR DKO (double knockout) mice, we showed that C3aR and C5aR deficiency together strikingly decreased both systolic and diastolic blood pressure in response to Ang II compared with WT (wild type), single C3aR-deficient (C3aR-/-), or C5aR-deficient (C5aR-/-) mice. Flow cytometric analysis showed that Ang II-induced Treg reduction in the kidney and blood was also blocked in DKO mice. Histological analysis indicated that renal and vascular structure remodeling and damage after Ang II treatment were attenuated in DKO mice compared with WT mice. In vitro, Ang II was able to stimulate C3aR and C5aR expression in cultured CD4+CD25+ natural Tregs. CD3 and CD28 antibody stimuli downregulated Foxp3 expression in WT but not DKO Tregs. More important, depletion of Tregs with CD25 antibody abolished the protective effects against Ang II-induced hypertension and target-organ damage in DKO mice. Adoptive transfer of DKO Tregs showed much more profound protective effects against Ang II-induced hypertension than WT Treg transfer. Furthermore, we demonstrated that C5aR expression in Foxp3+ Tregs was higher in hypertensive patients compared with normotensive individuals. Conclusions: C3aR and C5aR DKO-mediated Treg function prevents Ang II-induced hypertension and target-organ damage. Targeting C3aR and C5aR in Tregs specifically may be an alternative novel approach for hypertension treatment.
学科主题Cardiovascular System & Cardiology ; Hematology
WOS关键词END-ORGAN DAMAGE ; VASCULAR INFLAMMATION ; OXIDATIVE STRESS ; RENAL DAMAGE ; ACTIVATION ; INJURY ; MICE ; RATS ; CONTRIBUTES ; DYSFUNCTION
语种英语
WOS记录号WOS:000428709500016
出版者LIPPINCOTT WILLIAMS & WILKINS
版本出版稿
源URL[http://202.127.25.144/handle/331004/1002]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Chinese Acad Sci, Lab Vasc Biol, Shanghai Inst Biol Sci, Inst Hlth Sci, Beijing, Peoples R China;
2.Shanghai Jiao Tong Univ, Shanghai Inst Hypertens, Sch Med, Shanghai, Peoples R China;
3.Chinese Acad Sci, Key Lab Stem Cell Biol, Shanghai Inst Biol Sci, Inst Hlth Sci, Beijing, Peoples R China,
4.Shanghai Jiao Tong Univ, State Key Lab Med Genom, Shanghai Key Lab Hypertens, Dept Hypertens,Ruijin Hosp,Sch Med, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China;
推荐引用方式
GB/T 7714		 Chen, Xiao-Hui,Ruan, Cheng-Chao,Ge, Qian,et al. Deficiency of Complement C3a and C5a Receptors Prevents Angiotensin II-Induced Hypertension via Regulatory T Cells[J]. CIRCULATION RESEARCH,2018,122(7):970-983.
APA Chen, Xiao-Hui.,Ruan, Cheng-Chao.,Ge, Qian.,Ma, Yu.,Xu, Jian-Zhong.,...&,.(2018).Deficiency of Complement C3a and C5a Receptors Prevents Angiotensin II-Induced Hypertension via Regulatory T Cells.CIRCULATION RESEARCH,122(7),970-983.
MLA Chen, Xiao-Hui,et al."Deficiency of Complement C3a and C5a Receptors Prevents Angiotensin II-Induced Hypertension via Regulatory T Cells".CIRCULATION RESEARCH 122.7(2018):970-983.

入库方式： OAI收割

来源：上海营养与健康研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。