Bai Conghua, Yang Huihua, Zhao Lei, Liu Linlin, Guo Wenting, Yu Jie, Li Meng, Liu Miao, Lai Xuefeng, Zhang Xiaomin, Zhu Rui, Yang Liangle
Department of Occupational and Environmental Health, Key Laboratory of Environment & Health, Ministry of Education, And State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Environ Res. 2022 Sep;212(Pt D):113469. doi: 10.1016/j.envres.2022.113469. Epub 2022 May 16.
Phthalates exposure has been reported to be linked with arterial stiffness. However, the biological mechanisms underlying this association remain unclear. We conducted a panel study using 338 paired urine-blood samples by repeated measurements of 123 adults across 3 seasons to assess the potential mediating role of plasma microRNAs (miRNAs) in the association of phthalates exposure with arterial stiffness. We measured 10 urinary phthalate metabolites by gas chromatography-tandem mass spectrometry (GC-MS/MS) and 5 candidate arterial stiffness-related miRNAs (miR-146a, miR-222, miR-125b, miR-126, and miR-21) in plasma by real-time PCR. Arterial stiffness parameters including brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were determined in health examinations during each visit. Linear mixed-effect (LME) models revealed that mono-methyl phthalate (MMP), mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MBP), mono-n-octyl phthalate (MOP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) were significantly associated with one or more of the 5 plasma miRNAs (all P < 0.05). Based on weighted quantile sum (WQS) regression, we found positive associations of phthalate metabolites mixture with miR-146a, miR-125b, and miR-222, and individual MMP and MBP were the major contributors. Additionally, miR-146a was inversely related to ABI. Mediation analysis further indicated that miR-146a mediated 31.6% and 21.3% of the relationships of MMP and MiBP with ABI, respectively. Our findings suggested that certain phthalates exposure was related to plasma miRNAs alterations in a dose-response manner and miR-146a might partly mediate phthalate-associated ABI reduction.
据报道，邻苯二甲酸盐暴露与动脉僵硬度有关。然而，这种关联背后的生物学机制仍不清楚。我们进行了一项队列研究，对123名成年人在三个季节进行重复测量，采集了338对尿血样本，以评估血浆微小RNA（miRNA）在邻苯二甲酸盐暴露与动脉僵硬度关联中的潜在中介作用。我们通过气相色谱 - 串联质谱法（GC-MS/MS）测定了10种尿邻苯二甲酸酯代谢物，并通过实时PCR测定了血浆中5种与动脉僵硬度相关的候选miRNA（miR-146a、miR-222、miR-125b、miR-126和miR-21）。在每次就诊的健康检查中测定动脉僵硬度参数，包括臂踝脉搏波速度（baPWV）和踝臂指数（ABI）。线性混合效应（LME）模型显示，单甲基邻苯二甲酸酯（MMP）、单异丁基邻苯二甲酸酯（MiBP）、单正丁基邻苯二甲酸酯（MBP）、单正辛基邻苯二甲酸酯（MOP）和单（2-乙基-5-羧基戊基）邻苯二甲酸酯（MECPP）与5种血浆miRNA中的一种或多种显著相关（所有P < 0.05）。基于加权分位数和（WQS）回归，我们发现邻苯二甲酸酯代谢物混合物与miR-146a、miR-125b和miR-222呈正相关，个体MMP和MBP是主要贡献者。此外，miR-146a与ABI呈负相关。中介分析进一步表明，miR-146a分别介导了MMP和MiBP与ABI关系的31.6%和21.3%。我们的研究结果表明，某些邻苯二甲酸盐暴露以剂量反应方式与血浆miRNA改变有关，miR-146a可能部分介导邻苯二甲酸盐相关的ABI降低。
