Data from: Benzene exposure is associated with cardiovascular disease risk

Benzene is a ubiquitous, volatile pollutant present at high concentrations in toxins (e.g. tobacco smoke) known to increase cardiovascular disease (CVD) risk. Despite its prevalence, the cardiovascular effects of benzene have rarely been studied. Hence, we examined whether exposure to benzene is associated with increased CVD risk. The effects of benzene exposure in mice were assessed by direct inhalation, while the effects of benzene exposure in humans was assessed in 210 individuals with mild to high CVD risk by measuring urinary levels of the benzene metabolite trans,trans-muconic acid (t,t-MA). Generalized linear models were used to assess the association between benzene exposure and CVD risk. Mice inhaling volatile benzene had significantly reduced levels of circulating angiogenic cells (Flk-1+/Sca-1+) as well as an increased levels of plasma low-density lipoprotein (LDL) compared with control mice breathing filtered air. In the human cohort, urinary levels of t,t-MA were inversely associated several populations of circulating angiogenic cells (CD31+/34+/45+, CD31+/34+/45+/AC133–, CD34+/45+/AC133+). Although t,t-MA was not associated with plasma markers of inflammation or thrombosis, t,t-MA levels were higher in smokers and in individuals with dyslipidemia. In smokers, t,t-MA levels were positively associated with urinary metabolites of nicotine (cotinine) and acrolein (3-hydroxymercapturic acid). Levels of t,t-MA were also associated with CVD risk as assessed using the Framingham Risk Score and this association was independent of smoking. Thus, benzene exposure is associated with increased CVD risk and deficits in circulating angiogenic cells in both smokers and non-smokers.苯（Benzene）是一种无处不在的挥发性污染物，在已知会增加心血管疾病（cardiovascular disease, CVD）风险的毒素（如烟草烟雾）中浓度较高。尽管其分布广泛，但苯对心血管系统的影响鲜有研究。因此，本研究旨在探讨苯暴露是否与心血管疾病风险升高存在关联。研究通过直接吸入染毒的方式评估苯暴露对小鼠的影响；针对人类的苯暴露效应，则通过检测210名存在轻度至高心血管疾病风险的个体尿液中苯代谢产物反,反-粘康酸（trans,trans-muconic acid, t,t-MA）的水平进行评估。采用广义线性模型（generalized linear models）分析苯暴露与心血管疾病风险之间的关联。与吸入过滤空气的对照组小鼠相比，吸入挥发性苯的小鼠循环血管生成细胞（circulating angiogenic cells）Flk-1+/Sca-1+水平显著降低，同时血浆低密度脂蛋白（low-density lipoprotein, LDL）水平升高。在人类队列中，尿液t,t-MA水平与多个循环血管生成细胞亚群呈负相关，包括CD31+/34+/45+、CD31+/34+/45+/AC133–以及CD34+/45+/AC133+。尽管t,t-MA与血浆炎症或血栓形成标志物无显著关联，但吸烟者及血脂异常个体的尿液t,t-MA水平更高。在吸烟者群体中，t,t-MA水平与尼古丁代谢产物可替宁（cotinine）及丙烯醛代谢产物3-羟基巯基尿酸（3-hydroxymercapturic acid）的尿液水平呈正相关。尿液t,t-MA水平还与弗雷明汉风险评分（Framingham Risk Score）所评估的心血管疾病风险显著相关，且该关联独立于吸烟状态。综上，无论吸烟者还是非吸烟者，苯暴露均与心血管疾病风险升高及循环血管生成细胞缺陷相关。