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Open Access Highly Accessed Research article

Cholesterol efflux is LXRα isoform-dependent in human macrophages

A Zhi Sha Ma12, Zhi Yuan Song1* and Qian Zhang1*

Author Affiliations

1 Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing, China

2 Department of Cardiology, The fifth hospital of Chinese PLA, Yinchuan, China

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BMC Cardiovascular Disorders 2014, 14:80  doi:10.1186/1471-2261-14-80

Published: 4 July 2014

Abstract

Background

The 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.

Methods

We 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.

Results

Here 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.

Conclusions

These findings imply that LXRα- rather than LXRβ- specific agonists may promote reverse cholesterol transport in humans.

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