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dc.contributor.authorXiao, Hanen_US
dc.contributor.authorLu, Minen_US
dc.contributor.authorLin, Ting Yangen_US
dc.contributor.authorChen, Zhenen_US
dc.contributor.authorChen, Gangen_US
dc.contributor.authorWang, Wei-Chien_US
dc.contributor.authorMarin, Tracien_US
dc.contributor.authorShentu, Tzu-pinen_US
dc.contributor.authorWen, Liangen_US
dc.contributor.authorGongol, Brendanen_US
dc.contributor.authorSun, Weien_US
dc.contributor.authorLiang, Xiaoen_US
dc.contributor.authorChen, Juen_US
dc.contributor.authorHuang, Hsien-Daen_US
dc.contributor.authorPedra, Joao H. F.en_US
dc.contributor.authorJohnson, David A.en_US
dc.contributor.authorShyy, John Y-J.en_US
dc.date.accessioned2014-12-08T15:31:56Z-
dc.date.available2014-12-08T15:31:56Z-
dc.date.issued2013-08-06en_US
dc.identifier.issn0009-7322en_US
dc.identifier.urihttp://dx.doi.org/10.1161/CIRCULATIONAHA.113.002714en_US
dc.identifier.urihttp://hdl.handle.net/11536/22567-
dc.description.abstractBackground-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.en_US
dc.language.isoen_USen_US
dc.subjectatherosclerosisen_US
dc.subjectendothelial cellen_US
dc.subjectNLRP3 proteinen_US
dc.subjecthumanen_US
dc.subjectshear stressen_US
dc.subjectsterol regulatory element binding proteinsen_US
dc.titleSterol Regulatory Element Binding Protein 2 Activation of NLRP3 Inflammasome in Endothelium Mediates Hemodynamic-Induced Atherosclerosis Susceptibilityen_US
dc.typeArticleen_US
dc.identifier.doi10.1161/CIRCULATIONAHA.113.002714en_US
dc.identifier.journalCIRCULATIONen_US
dc.citation.volume128en_US
dc.citation.issue6en_US
dc.citation.spage632en_US
dc.citation.epage642en_US
dc.contributor.department生物資訊及系統生物研究所zh_TW
dc.contributor.departmentInstitude of Bioinformatics and Systems Biologyen_US
dc.identifier.wosnumberWOS:000322759200015-
dc.citation.woscount23-
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