Pregnane X Receptor Mediates Atherosclerosis Induced by Dicyclohexyl Phthalate in LDL Receptor-Deficient Mice.
Pregnane X Receptor Mediates Atherosclerosis Induced by Dicyclohexyl Phthalate in LDL Receptor-Deficient Mice.
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作者：
Liu J;Hernandez R;Li X;Meng Z;Chen H;Zhou C
塑料相关内分泌干扰物（EDCs）与人类心血管疾病（CVD）的病因有关，但其潜在机制仍不清楚。邻苯二甲酸二环己酯（DCHP）是一种广泛使用的邻苯二甲酸酯增塑剂;暴露于DCHP是否以及如何在体内引起不良反应大多是未知的。我们以前报道，DCHP是一个有效的配体的甾烷X受体（PXR），作为一个异生物质的传感器，以调节异生物质的代谢。PXR还在巨噬细胞中起作用，以调节动物模型中的动脉粥样硬化发展。在当前的研究中，使用具有骨髓特异性PXR缺陷（PXRΔMyeLDLR−/−）的LDL受体缺陷小鼠及其对照同窝仔（PXRF/FLDLR−/−）来确定DCHP暴露对巨噬细胞功能和动脉粥样硬化的影响。长期暴露于DCHP显著增加了PXRF/FLDLR−/−小鼠主动脉根部和头臂动脉的动脉粥样硬化病变面积，分别增加了65%和77%。相比之下，DCHP不会影响PXRΔMyeLDLR−/−小鼠的动脉粥样硬化发展。暴露于DCHP导致巨噬细胞中清道夫受体CD 36的表达升高，并增加PXRF/FLDLR−/−小鼠中巨噬细胞形成细胞。我们的研究结果提供了邻苯二甲酸酯相关CVD风险的潜在机制，并最终刺激进一步研究和减轻塑料相关EDCs对人类CVD风险的不良影响。
Plastic-associated endocrine disrupting chemicals (EDCs) have been implicated in the etiology of cardiovascular disease (CVD) in humans, but the underlying mechanisms remain elusive. Dicyclohexyl phthalate (DCHP) is a widely used phthalate plasticizer; whether and how exposure to DCHP elicits adverse effects in vivo is mostly unknown. We previously reported that DCHP is a potent ligand of the pregnane X receptor (PXR) which acts as a xenobiotic sensor to regulate xenobiotic metabolism. PXR also functions in macrophages to regulate atherosclerosis development in animal models. In the current study, LDL receptor-deficient mice with myeloid-specific PXR deficiency (PXRΔMyeLDLR−/−) and their control littermates (PXRF/FLDLR−/−) were used to determine the impact of DCHP exposure on macrophage function and atherosclerosis. Chronic exposure to DCHP significantly increased atherosclerotic lesion area in the aortic root and brachiocephalic artery of PXRF/FLDLR−/− mice by 65% and 77%, respectively. By contrast, DCHP did not affect atherosclerosis development in PXRΔMyeLDLR−/− mice. Exposure to DCHP led to elevated expression of the scavenger receptor CD36 in macrophages and increased macrophage form cell formation in PXRF/FLDLR−/− mice. Our findings provide potential mechanisms underlying phthalate-associated CVD risk and will ultimately stimulate further investigations and mitigation of the adverse effects of plastic-associated EDCs on CVD risk in humans.
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影响因子：
13.6
作者：
Geyer R;Jambeck JR;Law KL
通讯作者：
Law KL
基于柬埔寨总膳食研究的邻苯二甲酸酯膳食暴露和人类风险评估
影响因子：
8.3
作者：
Cheng, Zhang;Li, Han-Han;Wong, Ming-Hung
通讯作者：
Wong, Ming-Hung
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
DOI：
10.1080/19440049.2015.1079742
发表时间：
2015-11-02
影响因子：
2.9
作者：
Cao, Xu-Liang;Zhao, Wendy;Dabeka, Robert
通讯作者：
Dabeka, Robert
影响因子：
13.8
作者：
Dvořák Z;Sokol H;Mani S
通讯作者：
Mani S