Alhamdow Ayman, Lindh Christian, Albin Maria, Gustavsson Per, Tinnerberg Håkan, Broberg Karin
Institute of Environmental Medicine, Karolinska Institutet, Stockholm 171 77, Sweden.
Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund 223 63, Sweden.
Toxicol Sci. 2019 Sep 1;171(1):235-246. doi: 10.1093/toxsci/kfz142.
Chimney sweeps have higher incidence and mortality of cardiovascular disease (CVD), likely related to their exposure to polycyclic aromatic hydrocarbons (PAH). In order to identify underlying mechanisms of PAH-related CVD, we here investigated whether PAH exposure was associated with levels of putative CVD-related proteins in serum among currently working chimney sweeps. We enrolled 116 chimney sweeps and 125 unexposed controls, all nonsmoking male workers from Sweden. We measured monohydroxylated PAH metabolites in urine by liquid chromatography coupled to tandem mass spectrometry and a panel of 85 proteins in serum using proximity extension assay. Linear regression analysis adjusted for age and body mass index showed that 25 proteins were differentially expressed between chimney sweeps and the controls (p < .05, adjusted for false discovery rate). Of the 25 proteins, follistatin (FS), prointerleukin-16 (IL-16), and heat shock protein beta-1 (HSP 27) showed positive associations with the monohydroxylated metabolites of PAH in a dose-response manner (p < .05). Pathway and gene ontology analyses demonstrated that the differentially expressed proteins were mainly involved in inflammatory response and immunological functions, such as leukocyte migration, cell movement of leukocytes, and adhesion of immune cells. In conclusion, we found a number of putative CVD-related proteins differentially expressed, between PAH-exposed and unexposed individuals, and mainly involved in inflammation and immune function. Our data warrant protective measures to reduce PAH exposure and longitudinal investigations of the protein profile in chimney sweeps and other occupational groups exposed to PAH.
烟囱清扫工心血管疾病（CVD）的发病率和死亡率较高，这可能与他们接触多环芳烃（PAH）有关。为了确定PAH相关CVD的潜在机制，我们在此研究了当前在职的烟囱清扫工中，PAH暴露是否与血清中假定的CVD相关蛋白水平有关。我们招募了116名烟囱清扫工和125名未接触者作为对照，他们均为来自瑞典的不吸烟男性工人。我们通过液相色谱-串联质谱法测量尿液中的单羟基化PAH代谢物，并使用邻位延伸分析测定血清中的85种蛋白质。对年龄和体重指数进行调整后的线性回归分析表明，烟囱清扫工和对照组之间有25种蛋白质表达存在差异（p < 0.05，经错误发现率调整）。在这25种蛋白质中，卵泡抑素（FS）、前白细胞介素-16（IL-16）和热休克蛋白β-1（HSP 27）与PAH的单羟基化代谢物呈剂量反应关系（p < 0.05）。通路和基因本体分析表明，差异表达的蛋白质主要参与炎症反应和免疫功能，如白细胞迁移、白细胞的细胞运动以及免疫细胞的黏附。总之，我们发现一些假定的CVD相关蛋白在PAH暴露者和未暴露者之间存在差异表达，且主要参与炎症和免疫功能。我们的数据表明需要采取保护措施以减少PAH暴露，并对烟囱清扫工和其他暴露于PAH的职业群体的蛋白质谱进行纵向研究。
