Devlin Robert B, Smith Candice B, Schmitt Michael T, Rappold Ana G, Hinderliter Alan, Graff Don, Carraway Martha Sue
Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, North Carolina 27711
Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, North Carolina 27711.
Toxicol Sci. 2014 Jul;140(1):61-72. doi: 10.1093/toxsci/kfu063. Epub 2014 Apr 9.
Many studies have reported associations between air pollution particles with an aerodynamic diameter <2.5 μm (fine particulate matter (PM)) and adverse cardiovascular effects. However, there is an increased concern that so-called ultrafine PM which comprises the smallest fraction of fine PM (aerodynamic diameter <0.1 μm) may be disproportionately toxic relative to the 0.1-2.5 μm fraction. Ultrafine PM is not routinely measured in state monitoring networks and is not homogenously dispersed throughout an airshed but rather located in hot spots such as near combustion sources (e.g., roads), making it difficult for epidemiology studies to associate exposure to ultrafine PM with adverse health effects. Thirty four middle-aged individuals with metabolic syndrome were exposed for 2 h while at rest in a randomized crossover design to clean air and concentrated ambient ultrafine particles (UCAPS) for 2 h. To further define potential risk, study individuals carrying the null allele for GSTM1 (a prominent antioxidant gene) were identified by genotyping. Blood was obtained immediately prior to exposure, and at 1 and 20 h afterward. Continuous Holter monitoring began immediately prior to exposure and continued for 24 h. Based on changes we observed in previous CAPS studies, we hypothesized that ultrafine CAPS would cause changes in markers of blood inflammation and fibrinolysis as well as changes in heart rate variability and cardiac repolarization. GSTM1 null individuals had altered cardiac repolarization as seen by a change in QRS complexity following exposure to UCAPS and both the entire study population as well as GSTM1 null individuals had increased QT duration. Blood plasminogen and thrombomodulin were decreased in the whole population following UCAPS exposure, whereas C-reactive protein (CRP) and SAA were increased. This controlled human exposure study is the first to show that ambient ultrafine particles can cause cardiovascular changes in people with metabolic syndrome, which affects nearly a quarter of the U.S. adult population.
许多研究报告了空气动力学直径小于2.5微米的空气污染颗粒（细颗粒物（PM））与心血管不良影响之间的关联。然而，人们越来越担心，所谓的超细颗粒物，即细颗粒物中最小的部分（空气动力学直径小于0.1微米），相对于0.1 - 2.5微米的部分，可能具有不成比例的毒性。超细颗粒物在国家监测网络中并非常规测量项目，且并非均匀分布在整个空气流域，而是集中在热点区域，如燃烧源（如道路）附近，这使得流行病学研究难以将超细颗粒物暴露与不良健康影响联系起来。34名患有代谢综合征的中年个体在随机交叉设计中，在休息状态下暴露于清洁空气2小时，然后暴露于浓缩的环境超细颗粒物（UCAPS）2小时。为了进一步确定潜在风险，通过基因分型鉴定携带谷胱甘肽S - 转移酶M1（一种重要的抗氧化基因）无效等位基因的研究个体。在暴露前、暴露后1小时和20小时采集血液。连续动态心电图监测在暴露前立即开始，并持续24小时。基于我们在之前CAPS研究中观察到的变化，我们假设超细CAPS会导致血液炎症和纤维蛋白溶解标志物的变化，以及心率变异性和心脏复极化的变化。暴露于UCAPS后，GSTM1无效个体的QRS波群复杂性发生变化，提示心脏复极化改变，整个研究人群以及GSTM1无效个体的QT间期均延长。暴露于UCAPS后，全人群血浆纤溶酶原和血栓调节蛋白降低，而C反应蛋白（CRP）和血清淀粉样蛋白A（SAA）升高。这项受控人体暴露研究首次表明，环境超细颗粒物可导致代谢综合征患者出现心血管变化，而代谢综合征影响着近四分之一的美国成年人口。
