Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP5039 |
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 | |
Hu, Wenxin1; Jia, Yingting1; Kang, Qiyue1; Peng, Hui2; Ma, Haojia1; Zhang, Shiyi1; Hiromori, Youhei3,4; Kimura, Tomoki5; Nakanishi, Tsuyoshi3; Zheng, Lemin6; Qiu, Yifu7; Zhang, Zhaobin1; Wan, Yi1; Hu, Jianying1 | |
2019-11-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES |
ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2019 |
卷号 | 127期号:11 |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; Canada; Japan |
英文摘要 | 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 ApoE mouse model. METHODS: We used a His-LXRa-pull-down assay and a nontarget high-resolution mass spectrometry method to screen house dust collected from Chinese homes for LXRct- and LX10-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, AJ3CA1 and ABCGI, and finally to induce atherosclerotic lesions in vivo using an ApoE(-/-) 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 ApoE(-/-) 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 ApoE(-/-) mouse model. These results highlight the need to assess the LXRantagonist activities of pollutants in future environmental management programs. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000500762600004 |
WOS关键词 | ORGANOPHOSPHORUS FLAME RETARDANTS ; 2-ETHYLHEXYL DIPHENYL PHOSPHATE ; REVERSE CHOLESTEROL TRANSPORT ; METABOLIC DYSFUNCTIONS ; TRIPHENYL PHOSPHATE ; APOLIPOPROTEIN-E ; LIGAND-BINDING ; PPAR-GAMMA ; EFFLUX ; ABCA1 |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/224618 |
专题 | 环境与发展全球科技态势 |
作者单位 | 1.Peking Univ, Coll Urban & Environm Sci, Lab Earth Surface Proc, Beijing 10087, Peoples R China; 2.Univ Toronto, Dept Chem, Toronto, ON, Canada; 3.Gifu Pharmaceut Univ, Lab Hyg Chem & Mol Toxicol, Gifu, Gifu, Japan; 4.Suzuka Univ Med Sci, Fac Pharmaceut Sci, Suzuka, Mie, Japan; 5.Setsunan Univ, Fac Sci & Engn, Dept Life Sci, Ikedanakamachi, Neyagawa, Osaka, Japan; 6.Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Beijing, Peoples R China; 7.Peking Univ, Inst Mol Med, Beijing, Peoples R China |
推荐引用方式 GB/T 7714 | Hu, Wenxin,Jia, Yingting,Kang, Qiyue,et al. 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[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2019,127(11). |
APA | Hu, Wenxin.,Jia, Yingting.,Kang, Qiyue.,Peng, Hui.,Ma, Haojia.,...&Hu, Jianying.(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,127(11). |
MLA | Hu, Wenxin,et al."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 127.11(2019). |
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