China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Environ Health Perspect. 2024 Sep;132(9):97005. doi: 10.1289/EHP13864. Epub 2024 Sep 6.
Environmental contaminants (ECs) are increasingly recognized as crucial drivers of dyslipidemia and cardiovascular disease (CVD), but the comprehensive impact spectrum and interlinking mechanisms remain uncertain.
We aimed to systematically evaluate the association between exposure to 80 ECs across seven divergent categories and markers of dyslipidemia and investigate their underpinning biomolecular mechanisms via an unbiased integrative approach of internal chemical exposome and multi-omics.
A longitudinal study involving 76 healthy older adults was conducted in Jinan, China, and participants were followed five times from 10 September 2018 to 19 January 2019 in 1-month intervals. A broad spectrum of seven chemical categories covering the prototypes and metabolites of 102 ECs in serum or urine as well as six serum dyslipidemia markers [total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein (Apo)A1, ApoB, and ApoE4] were measured. Multi-omics, including the blood transcriptome, serum/urine metabolome, and serum lipidome, were profiled concurrently. Exposome-wide association study and the deletion/substitution/addition algorithms were applied to explore the associations between 80 EC exposures detection frequency and dyslipidemia markers. Weighted quantile sum regression was used to assess the mixture effects and relative contributions. Multi-omics profiling, causal inference model, and pathway analysis were conducted to interpret the mediating biomolecules and underlying mechanisms. Examination of cytokines and electrocardiograms was further conducted to validate the observed associations and biomolecular pathways.
Eight main ECs [1-naphthalene, 1-pyrene, 2-fluorene, dibutyl phosphate, tri-phenyl phosphate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, chromium, and vanadium] were significantly associated with most dyslipidemia markers. Multi-omics indicated that the associations were mediated by endogenous biomolecules and pathways, primarily pertinent to CVD, inflammation, and metabolism. Clinical measures of cytokines and electrocardiograms further cross-validated the association of these exogenous ECs with systemic inflammation and cardiac function, demonstrating their potential mechanisms in driving dyslipidemia pathogenesis.
It is imperative to prioritize mitigating exposure to these ECs in the primary prevention and control of the dyslipidemia epidemic. https://doi.org/10.1289/EHP13864.
环境污染物（ECs）日益被认为是导致血脂异常和心血管疾病（CVD）的关键驱动因素，但综合影响谱和相互关联的机制仍不确定。
我们旨在通过内部化学暴露组学和多组学的无偏整合方法，系统评估 7 个不同类别中 80 种 ECs 暴露与血脂异常标志物之间的关联，并研究其潜在的生物分子机制。
在中国济南进行了一项纵向研究，纳入了 76 名健康老年人，参与者于 2018 年 9 月 10 日至 2019 年 1 月 19 日期间每隔 1 个月随访 5 次。我们同时测量了血清或尿液中 102 种 EC 原型和代谢物以及 6 种血清血脂异常标志物[总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白（Apo）A1、ApoB 和 ApoE4]的广泛谱。并行分析了多组学，包括血液转录组、血清/尿液代谢组和血清脂质组。应用暴露组全关联研究和缺失/替换/添加算法来探讨 80 种 EC 暴露检测频率与血脂异常标志物之间的关系。加权分位数总和回归用于评估混合物效应和相对贡献。多组学分析、因果推断模型和通路分析用于解释介导的生物分子和潜在机制。进一步进行了细胞因子和心电图检查以验证观察到的关联和生物分子通路。
8 种主要 ECs[1-萘、1-蒽、2-芴、磷酸二丁酯、磷酸三苯酯、邻苯二甲酸单（2-乙基-5-羟基己基）酯、铬和钒]与大多数血脂异常标志物显著相关。多组学表明，这些关联是由内源性生物分子和途径介导的，主要与 CVD、炎症和代谢有关。细胞因子和心电图的临床测量进一步交叉验证了这些外源性 ECs 与全身炎症和心脏功能的关联，表明它们在驱动血脂异常发病机制中的潜在机制。
在血脂异常流行的一级预防和控制中，优先考虑减轻这些 ECs 的暴露至关重要。https://doi.org/10.1289/EHP13864.
