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Sterol Regulatory Element Binding Protein 2 Activation of NLRP3 Inflammasome in Endothelium Mediates Hemodynamic-Induced Atherosclerosis Susceptibility
Xiao, Han1,4; Lu, Min5; Lin, Ting Yang1; Chen, Zhen1,5; Chen, Gang2,3; Wang, Wei-Chi6; Marin, Traci1; Shentu, Tzu-pin1; Wen, Liang1; Gongol, Brendan1; Sun, Wei1; Liang, Xiao7; Chen, Ju5; Huang, Hsien-Da6; Pedra, Joao H. F.2,3; Johnson, David A.1; Shyy, John Y-J.1,5,7
关键词atherosclerosis endothelial cell NLRP3 protein human shear stress sterol regulatory element binding proteins
刊名CIRCULATION
2013-08-06
DOI10.1161/CIRCULATIONAHA.113.002714
128期:6页:632-642
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Peripheral Vascular Disease
资助者National Institutes of Health ; National Natural Science Foundation of China ; National Science Council of the Republic of China ; UST-UCSD I-RiCE Program ; National Institutes of Health ; National Natural Science Foundation of China ; National Science Council of the Republic of China ; UST-UCSD I-RiCE Program
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]CHRONIC GRANULOMATOUS-DISEASE ; SHEAR-STRESS ; CHOLESTEROL HOMEOSTASIS ; RECEPTOR ANTAGONIST ; HEART-DISEASE ; UP-REGULATION ; CELLS ; MICE ; INTERLEUKIN-1-BETA ; REGIONS
英文摘要

Background-The molecular basis for the focal nature of atherosclerotic lesions is poorly understood. Here, we explored whether disturbed flow patterns activate an innate immune response to form the NLRP3 inflammasome scaffold in vascular endothelial cells via sterol regulatory element binding protein 2 (SREBP2).

Methods and Results-Oscillatory flow activates SREBP2 and induces NLRP3 inflammasome in endothelial cells. The underlying mechanisms involve SREBP2 transactivating NADPH oxidase 2 and NLRP3. Consistently, SREBP2, NADPH oxidase 2, and NLRP3 levels were elevated in atheroprone areas of mouse aortas, suggesting that the SREBP2-activated NLRP3 inflammasome causes functionally disturbed endothelium with increased inflammation. Mimicking the effect of atheroprone flow, endothelial cell-specific overexpression of the activated form of SREBP2 synergized with hyperlipidemia to increase atherosclerosis in the atheroresistant areas of mouse aortas.

Conclusions-Atheroprone flow induces NLRP3 inflammasome in endothelium through SREBP2 activation. This increased innate immunity in endothelium synergizes with hyperlipidemia to cause topographical distribution of atherosclerotic lesions.

语种英语
所属项目编号HL89940 ; HL105318 ; 81270349 ; NSC 101-2311-B-009-003-MY3 ; NSC 100-2627-B-009-002 ; NSC 101-2911-I-009-101
资助者National Institutes of Health ; National Natural Science Foundation of China ; National Science Council of the Republic of China ; UST-UCSD I-RiCE Program ; National Institutes of Health ; National Natural Science Foundation of China ; National Science Council of the Republic of China ; UST-UCSD I-RiCE Program
WOS记录号WOS:000322759200015
引用统计
被引频次:78[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66585
专题北京大学第三临床医学院_心血管内科
作者单位1.Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA
2.Univ Calif Riverside, Ctr Dis Vector Res, Riverside, CA 92521 USA
3.Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA
4.Peking Univ, Inst Vasc Med, Hosp 3, Beijing 100871, Peoples R China
5.Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
6.Natl Chiao Tung Univ, Dept Biol Sci & Technol, Inst Bioinformat & Syst Biol, Hsinchu, Taiwan
7.Xi An Jiao Tong Univ, Cardiovasc Res Ctr, Sch Med, Xian 710049, Peoples R China
推荐引用方式
GB/T 7714
Xiao, Han,Lu, Min,Lin, Ting Yang,et al. Sterol Regulatory Element Binding Protein 2 Activation of NLRP3 Inflammasome in Endothelium Mediates Hemodynamic-Induced Atherosclerosis Susceptibility[J]. CIRCULATION,2013,128(6):632-642.
APA Xiao, Han.,Lu, Min.,Lin, Ting Yang.,Chen, Zhen.,Chen, Gang.,...&Shyy, John Y-J..(2013).Sterol Regulatory Element Binding Protein 2 Activation of NLRP3 Inflammasome in Endothelium Mediates Hemodynamic-Induced Atherosclerosis Susceptibility.CIRCULATION,128(6),632-642.
MLA Xiao, Han,et al."Sterol Regulatory Element Binding Protein 2 Activation of NLRP3 Inflammasome in Endothelium Mediates Hemodynamic-Induced Atherosclerosis Susceptibility".CIRCULATION 128.6(2013):632-642.
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