Cholesterol efflux is LXRα isoform-dependent in human macrophages

BMC Cardiovascular Disorders

Research Article

Zhi Yuan Song¹  Qian Zhang¹  A Zhi Sha Ma² 

[1] Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing, China;Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing, China;Department of Cardiology, The fifth hospital of Chinese PLA, Yinchuan, China;

关键词: Reverse cholesterol transport;    Liver X receptor;    siRNA;    ABC transporter;    Atherosclerosis;   

DOI  :  10.1186/1471-2261-14-80

 received in 2014-02-21, accepted in 2014-06-26,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe nuclear receptor liver X receptor (LXR) has two isoforms: LXRα and LXRβ. LXR activation promotes cholesterol efflux in macrophages, but the relative importance of each LXR isoform in mediating cholesterol efflux remains elusive.MethodsWe evaluated the ability of different doses of LXRs agonist T0901317 to affect cholesterol efflux in human macrophages and its relationship with mRNA and protein levels of several well-characterized proteins involved in cholesterol efflux, including ABCA1, ABCG1, SR-BI, LXRβ and LXRα, using quantitative real-time PCR, Western blotting, and siRNA techniques.ResultsHere we show that LXRα rather than LXRβ sustains baseline cholesterol efflux in human blood-derived macrophages. Treatment of human macrophages with a non-isoform-specific LXR agonist T0901317 substantially increased HDL- and apoA-I-mediated cholesterol efflux, which was associated with increased mRNA and protein expression levels of ABCA1, ABCG1, SR-BI, LXRα and LXRβ. The siRNA- mediated silencing of LXRα, but not LXRβ significantly reduced the protein levels of ABCA1,ABCG1, and SR-BI as wellas HDL- and ApoA1-mediated cholesterol in human macrophages.ConclusionsThese findings imply that LXRα- rather than LXRβ- specific agonists may promote reverse cholesterol transport in humans.

【 授权许可】

Unknown   
© Ma et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.