Nov 15, 2019

Screening of House Dust from Chinese Homes for Chemicals with Liver X Receptors Binding Activities and Characterization of Atherosclerotic Activity Using an in Vitro Macrophage Cell Line and ApoE - / - Mice

Environmental Health Perspectives
Wenxin HuJianying Hu

Abstract

Atherosclerotic cardiovascular disease has become the leading cause of death worldwide, and environmental pollutants are increasingly recognized as risk factors for atherosclerosis. Liver X receptors (LXRs) play a central role in atherosclerosis; however, LXR activity of organic pollutants and associated potential risk of atherosclerosis have not yet been characterized. This study aimed to explore whether LXR-antagonistic chemicals are present in indoor house dust and, if so, to characterize this activity in relation to changes in macrophages in vitro and cardiovascular disease indicators in vivo in an atherosclerosis ApoE - / - mouse model. We used a His-LXR α -pull -down assay and a nontarget high-resolution mass spectrometry method to screen house dust collected from Chinese homes for LXR α - and LXR β -antagonist activity. A chemical identified in this manner was assessed for its ability to induce cholesterol efflux and foam cell formation in RAW264.7 macrophages, to down-regulate the expression of two LXR-dependent genes, ABCA1 and ABCG1, and finally to induce atherosclerotic lesions in vivo using an ApoE - / - mouse model. We identified the flame retardants triphenyl phosphate (TPHP) and 2-eth...Continue Reading

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Mentioned in this Paper

diphenyl methyl phosphate
Study
In Vivo
Protein Binding
Environment
Cessation of Life
Home Environment
Cardiovascular Diseases
Mass Spectrometry
ATP Binding Cassette Transporter, Sub-Family G, Member 1

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