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学科主题: 基础医学
题名:
Oxidized LDL downregulates ATP-binding cassette transporter-1 in human vascular endothelial cells via inhibiting liver X receptor (LXR)
作者: Zhu, Y; Liao, HL; Xie, XF; Yuan, Y; Lee, TS; Wang, NP; Wang, X; Shyy, JYJ; Stemerman, MB
关键词: cholesterol ; endothelial function ; gene expression ; lipoprotein ; membrane transport
刊名: CARDIOVASCULAR RESEARCH
发表日期: 2005-12-01
DOI: 10.1016/j.cardiores.2005.07.003
卷: 68, 期:3, 页:425-432
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems
研究领域[WOS]: Cardiovascular System & Cardiology
关键词[WOS]: LOW-DENSITY-LIPOPROTEIN ; REVERSE CHOLESTEROL TRANSPORT ; STEROL 27-HYDROXYLASE ; SCAVENGER RECEPTOR ; TANGIER-DISEASE ; EFFLUX ; MACROPHAGES ; CAVEOLAE ; ABCA1 ; EXPRESSION
英文摘要:

Objective: ATP-binding cassette transporter-1 (ABCA1) mediates the active efflux of cholesterol and phospholipids, playing an important role in cholesterol homeostasis and atherogenesis. Oxidized low density lipoprotein (oxLDL) is an atherogenic molecule associated with the vascular endothelial dysfunction and development of atherosclerotic plaque. This report describes the effect of copper-catalyzed oxLDL on the regulation of ABCA1 in human endothelial cells (ECs).

Methods and results: oxLDL downregulated ABCA1 at both mRNA and protein levels in a dose-dependent manner. This inhibitory effect of oxLDL was observed with both minimally and extensively oxLDL. Transfection of the ABCA1 promoter luciferase revealed oxLDL to substantially decrease ABCA1 promoter activity at basal conditions and after stimulation by overexpressing the liver X receptor LXR alpha and retinoid X receptor RXR alpha. oxLDL also attenuated LXR activation by blocking LXR ligand binding and interfering with the generation of 27-hydroxycholesterol, an LXR endogenous ligand. Furthermore, oxLDL inhibited exogenous cholesterol- and oxysterol-induced endothelial ABCA1 induction.

Conclusion: oxLDL downregulated ABCA1 by inhibiting LXR activation in endothelial cells. Such an effect may contribute to endothelial dysfunction and plaque formation. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

语种: 英语
WOS记录号: WOS:000233469400013
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57192
Appears in Collections:基础医学院_生理学与病理生理学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Physiol, Key Lab Mol Cardiovasc Sci,Educ Minist, Beijing 100083, Peoples R China
2.Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA

Recommended Citation:
Zhu, Y,Liao, HL,Xie, XF,et al. Oxidized LDL downregulates ATP-binding cassette transporter-1 in human vascular endothelial cells via inhibiting liver X receptor (LXR)[J]. CARDIOVASCULAR RESEARCH,2005,68(3):425-432.
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