Abstract：
While the cardiovascular system is a primary target of organophosphorus flame retardants (OPFRs), particularly aryl-OPFRs, it is still exclusive whether the diisodecyl phenyl phosphate (DIDPP), widely used and broadly present in the environment at high concentrations, elicits atherosclerosis effects. Liver X receptors (LXRs) play a direct role in regulating the formation of atherosclerotic lesions. This study was the first to demonstrate that DIDPP acts as an LXRα ligand and functions as an LXRα antagonist with a half-maximal inhibitory concentration of 16.2 μM. We showed that treatment of an in vitro macrophage model with 1 to 10 μM of DIDPP resulted in the downregulation of direct targets of LXRα, namely ABCA1, ABCG1 and SR-B1, thereby leading to a 7.9-13.2 % reduction in cholesterol efflux. This caused dose-dependent, 24.1-43.1 % increases in the staining intensity of foam cells in the macrophage model. This atherosclerotic effect of DIDPP was proposed to be due to its antagonism of LXRα activity, as DIDPP treatment did not alter cholesterol influx. In conclusion, the findings of this study demonstrate that exposure to DIDPP may be a risk factor for atherosclerosis due to the LXRα-antagonistic activity of DIDPP and its ubiquity in the environment.
摘要：
虽然心血管系统是有机磷阻燃剂（OPFRs）的主要目标，特别是芳基-OPFR，它仍然是唯一的二异癸基苯基磷酸酯(DIDPP)，广泛使用和广泛存在于环境中的高浓度，引起动脉粥样硬化的影响。肝X受体(LXRs)在调控动脉粥样硬化病变的形成中起直接感化。这项研究首次证明DIDPP充当LXRα配体，并充当LXRα拮抗剂，其半数最大抑制浓度为16.2μM。我们表明，用1至10μM的DIDPP处理体外巨噬细胞模型会导致LXRα的直接靶标下调，即ABCA1，ABCG1和SR-B1，从而导致胆固醇外排减少7.9-13.2％。这导致剂量依赖性，巨噬细胞模型中泡沫细胞的染色强度增加了24.1-43.1％。DIDPP的这种动脉粥样硬化作用被认为是由于其对LXRα活性的拮抗作用，因为DIDPP治疗没有改变胆固醇流入。总之,这项研究的结果表明,由于DIDPP的LXRα拮抗活性及其在环境中的普遍存在,DIDPP暴露可能是动脉粥样硬化的危险因素.
