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01.12.2014 | Research article | Ausgabe 1/2014 Open Access

BMC Cardiovascular Disorders 1/2014

Cholesterol efflux is LXRα isoform-dependent in human macrophages

Zeitschrift:
BMC Cardiovascular Disorders > Ausgabe 1/2014
Autoren:
A Zhi Sha Ma, Zhi Yuan Song, Qian Zhang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1471-2261-14-80) contains supplementary material, which is available to authorized users.
Zhi Yuan Song and Qian Zhang contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

AZSM designed the experiments and wrote the manuscript; AZSM carried out cell culture, the molecular genetic studies, the immunoassays and inhibition using LXR siRNA. ZYS participated in study design andcoordination and helped to draft the manuscript. All authors read and approved the final manuscript. QZ performed cellular cholesterol efflux experiments and statistical analyses.

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.
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