@article {127, title = {Screening of House Dust from Chinese Homes for Chemicals with Liver X Receptors Binding Activities and Characterization of Atherosclerotic Activity Using an Macrophage Cell Line and Mice.}, journal = {Environ Health Perspect}, volume = {127}, year = {2019}, month = {2019 11}, pages = {117003}, abstract = {

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 and cardiovascular disease indicators in an atherosclerosis mouse model.

METHODS: We used a -down assay and a nontarget high-resolution mass spectrometry method to screen house dust collected from Chinese homes for - and -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, and , and finally to induce atherosclerotic lesions using an 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 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 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.

}, keywords = {Air Pollutants, Air Pollution, Indoor, Animals, Atherosclerosis, China, Dust, Liver X Receptors, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, ApoE, RAW 264.7 Cells}, issn = {1552-9924}, doi = {10.1289/EHP5039}, author = {Hu, Wenxin and Jia, Yingting and Kang, Qiyue and Peng, Hui and Ma, Haojia and Zhang, Shiyi and Hiromori, Youhei and Kimura, Tomoki and Nakanishi, Tsuyoshi and Zheng, Lemin and Qiu, Yifu and Zhang, Zhaobin and Wan, Yi and Hu, Jianying} } @article {104, title = {p,p{\textquoteright}-DDE Induces Gonadal Intersex in Japanese Medaka (Oryzias latipes) at Environmentally Relevant Concentrations: Comparison with o,p{\textquoteright}-DDT.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 Jan 05}, pages = {462-9}, abstract = {

Previous studies have reported high body burdens of dichlorodiphenyltrichloroethane (DDT) and its metabolites in wild fishes worldwide. This study evaluated the adverse effects of 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p{\textquoteright}-DDE) and o,p{\textquoteright}-DDT on gonadal development and reproduction by exposing transgenic Japanese medaka (Oryzias latipes) from hatch for 100 days. While both p,p{\textquoteright}-DDE and o,p{\textquoteright}-DDT induced intersex in male medaka, the lowest observable effective concentration (LOEC) of o,p{\textquoteright}-DDT was 57.7 ng/g ww, about 5-fold lower than that (272 ng/g ww) of p,p{\textquoteright}-DDE. Since LOECs of both chemicals were comparable to the body concentrations in wild fish, DDT contamination would likely contribute to the occurrence of intersex observed in wild fish. Exposure to o,p{\textquoteright}-DDT resulted in much higher expression of vitellogenin in liver of males than p,p{\textquoteright}-DDE, accordant with the higher potency of o,p{\textquoteright}-DDT than p,p{\textquoteright}-DDE to induce intersex. This phenomenon could be partly explained by the significantly elevated levels of 17β-estradiol in plasma of males exposed to o,p{\textquoteright}-DDT, in addition to its estrogenic activity via the estrogen receptor. Significantly lower fertilization (p = 0.006) and hatchability (p = 0.019) were observed in the 13 intersex males. This study for the first time demonstrated the induction of intersex and reproductive effects of p,p{\textquoteright}-DDE and o,p{\textquoteright}-DDT at environmentally relevant concentrations.

}, keywords = {Animals, DDT, Dichlorodiphenyl Dichloroethylene, Disorders of Sex Development, Estradiol, Gonads, Male, Oryzias, Vitellogenins, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.5b05042}, author = {Sun, Jianxian and Wang, Chen and Peng, Hui and Zheng, Guomao and Zhang, Shiyi and Hu, Jianying} } @article {113, title = {High-density lipoprotein of patients with type 2 diabetes mellitus upregulates cyclooxgenase-2 expression and prostacyclin I-2 release in endothelial cells: relationship with HDL-associated sphingosine-1-phosphate.}, journal = {Cardiovasc Diabetol}, volume = {12}, year = {2013}, month = {2013 Jan 30}, pages = {27}, abstract = {

BACKGROUND: Dysfunctional high-density lipoprotein (HDL) may have pro-inflammatory effects on the endothelial cells,which causes atherosclerosis in type 2 diabetes mellitus (T2DM). HDL is a major carrier of sphingosine-1-phosphate (S1P) in plasma while S1P exhibits multiple biological activities. However, potential role of HDL and S1P in T2DM remains unexplored. We hypothesized that diabetic HDL with higher contents of S1P exerts beneficial effects on the vascular system.

METHODS: Subjects with T2DM with or without proved large arteries atherosclerosis and normal controls (n=15 for each group) were recruited in the present study. HDL was isolated from the subjects by ultracentrifugation. The levels of HDL-associated S1P were determined by UPLC-MS/MS. The protective function of diabetic HDL and S1P was evaluated by measuring cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release by human umbilical vein endothelial cells (HUVECs) using western blot and enzyme-linked immunosorbent assay (ELISA), respectively.

RESULTS: The S1P levels in isolated HDL were significantly increased in T2DM subjects compared with controls (235.6 {\textpm} 13.4 vs 195.0 {\textpm} 6.4 ng/mg, P\< 0.05). The diabetic HDL exerted greater protective effects on inducing COX-2 expression and PGI-2 release by HUVECs than those of control HDL (p \< 0.05, p \< 0.01, respectively). Pertussis toxin, a common inhibitor of G-couple protein receptors, and VPC 23019, an antagonist of S1P receptor 1 and 3 significantly attenuated HDL-induced COX-2 expression and PGI-2 release.

CONCLUSIONS: Diabetic HDL carries higher level of S1P compared with normal HDL, which has the potential to contribute to protective effects on endothelial cells by inducing COX-2 expression and PGI-2 release. These findings provide a new insight of S1P function in T2DM patients, possibly leading to a new therapeutic target.

}, keywords = {Adult, Aged, Cells, Cultured, Cyclooxygenase 2, Diabetes Mellitus, Type 2, Endothelial Cells, Epoprostenol, Female, Gene Expression Regulation, Enzymologic, Human Umbilical Vein Endothelial Cells, Humans, Lipoproteins, HDL, Lysophospholipids, Male, Middle Aged, Sphingosine, Up-Regulation}, issn = {1475-2840}, doi = {10.1186/1475-2840-12-27}, author = {Tong, Xunliang and Peng, Hui and Liu, Donghui and Ji, Liang and Niu, Chenguang and Ren, Jun and Pan, Bing and Hu, Jianying and Zheng, Lemin and Huang, Yining} }