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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 [Formula: see text] Mice
BACKGROUND: 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 pollutan...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Environmental Health Perspectives
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927504/ https://www.ncbi.nlm.nih.gov/pubmed/31724879 http://dx.doi.org/10.1289/EHP5039 |
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author | Hu, Wenxin Jia, Yingting Kang, Qiyue Peng, Hui Ma, Haojia Zhang, Shiyi Hiromori, Youhei Kimura, Tomoki Nakanishi, Tsuyoshi Zheng, Lemin Qiu, Yifu Zhang, Zhaobin Wan, Yi Hu, Jianying |
author_facet | Hu, Wenxin Jia, Yingting Kang, Qiyue Peng, Hui Ma, Haojia Zhang, Shiyi Hiromori, Youhei Kimura, Tomoki Nakanishi, Tsuyoshi Zheng, Lemin Qiu, Yifu Zhang, Zhaobin Wan, Yi Hu, Jianying |
author_sort | Hu, Wenxin |
collection | PubMed |
description | BACKGROUND: 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. OBJECTIVES: 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 [Formula: see text] mouse model. METHODS: We used a [Formula: see text]-down assay and a nontarget high-resolution mass spectrometry method to screen house dust collected from Chinese homes for [Formula: see text]- and [Formula: see text]-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 [Formula: see text] mouse model. RESULTS: We identified the flame retardants triphenyl phosphate (TPHP) and 2-ethylhexyl diphenyl phosphate (EHDPP) in house dust samples and demonstrated their ability to antagonize LXRs. The potency of TPHP was similar to that of the LXR-antagonist SR9238. TPHP could also inhibit cholesterol efflux and promote foam cell formation in RAW264.7 macrophages and mouse peritoneal macrophages and significantly promoted atherosclerotic lesion formation in the [Formula: see text] mouse model. CONCLUSIONS: We found LXR-antagonist chemicals in environmental samples of indoor dust from Chinese homes. One of the chemicals, TPHP, was able to promote the development of atherosclerotic lesions in the [Formula: see text] mouse model. These results highlight the need to assess the LXR-antagonist activities of pollutants in future environmental management programs. https://doi.org/10.1289/EHP5039 |
format | Online Article Text |
id | pubmed-6927504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Environmental Health Perspectives |
record_format | MEDLINE/PubMed |
spelling | pubmed-69275042019-12-24 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 [Formula: see text] Mice Hu, Wenxin Jia, Yingting Kang, Qiyue Peng, Hui Ma, Haojia Zhang, Shiyi Hiromori, Youhei Kimura, Tomoki Nakanishi, Tsuyoshi Zheng, Lemin Qiu, Yifu Zhang, Zhaobin Wan, Yi Hu, Jianying Environ Health Perspect Research BACKGROUND: 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. OBJECTIVES: 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 [Formula: see text] mouse model. METHODS: We used a [Formula: see text]-down assay and a nontarget high-resolution mass spectrometry method to screen house dust collected from Chinese homes for [Formula: see text]- and [Formula: see text]-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 [Formula: see text] mouse model. RESULTS: We identified the flame retardants triphenyl phosphate (TPHP) and 2-ethylhexyl diphenyl phosphate (EHDPP) in house dust samples and demonstrated their ability to antagonize LXRs. The potency of TPHP was similar to that of the LXR-antagonist SR9238. TPHP could also inhibit cholesterol efflux and promote foam cell formation in RAW264.7 macrophages and mouse peritoneal macrophages and significantly promoted atherosclerotic lesion formation in the [Formula: see text] mouse model. CONCLUSIONS: We found LXR-antagonist chemicals in environmental samples of indoor dust from Chinese homes. One of the chemicals, TPHP, was able to promote the development of atherosclerotic lesions in the [Formula: see text] mouse model. These results highlight the need to assess the LXR-antagonist activities of pollutants in future environmental management programs. https://doi.org/10.1289/EHP5039 Environmental Health Perspectives 2019-11-14 /pmc/articles/PMC6927504/ /pubmed/31724879 http://dx.doi.org/10.1289/EHP5039 Text en EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. |
spellingShingle | Research Hu, Wenxin Jia, Yingting Kang, Qiyue Peng, Hui Ma, Haojia Zhang, Shiyi Hiromori, Youhei Kimura, Tomoki Nakanishi, Tsuyoshi Zheng, Lemin Qiu, Yifu Zhang, Zhaobin Wan, Yi Hu, Jianying 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 [Formula: see text] Mice |
title | 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 [Formula: see text] Mice |
title_full | 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 [Formula: see text] Mice |
title_fullStr | 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 [Formula: see text] Mice |
title_full_unstemmed | 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 [Formula: see text] Mice |
title_short | 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 [Formula: see text] Mice |
title_sort | 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 [formula: see text] mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927504/ https://www.ncbi.nlm.nih.gov/pubmed/31724879 http://dx.doi.org/10.1289/EHP5039 |
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