title: Inflammatory response and endothelial dysfunction in the hearts of mice co-exposed to SO2, NO2, and PM2.5.
abstract: SO2, NO2, and PM2.5are typical air pollutants produced during the combustion of coal. Increasing evidence indicates that air pollution has contributed to the development and progression of heart-related diseases over the past decades. However, little experimental data and few studies of SO2, NO2, and PM2.5co-exposure in animals exist; therefore, the relevant mechanisms underlying this phenomenon are unclear. An important characteristic of air pollution is that co-exposure persists at a low concentration throughout a lifetime. In the present study, we treated adult mice with SO2, NO2, and PM2.5at various concentrations (0.5 mg/m3SO2, 0.2 mg/m3NO26 h/d, with intranasal instillation of 1 mg/kg PM2.5every other day during these exposures; or 3.5 mg/m3SO2, 2 mg/m3NO26 h/d, and 10 mg/kg PM2.5for 28 d). Blood pressure (BP), heart rate (HR), histopathological damage, and inflammatory and endothelial cytokines in the heart were assessed. The results indicate that co-exposure caused endothelial dysfunction by elevating endothelin-1 (ET-1) expression and repressing the endothelial nitric oxide synthase (eNOS) level as well as stimulating the inflammatory response by increasing the levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Additionally, these alterations were confirmed by histological staining. Furthermore, we observed decreased BP and increased HR after co-exposure. Our results indicate that co-exposure to SO2, NO2, and PM2.5may be a major risk factor for cardiac disease and may induce injury to the hearts of mammals and contribute to heart disease. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1996-2005, 2016.
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Ji
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ku
authors.affiliation: College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sang
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000633:toxicity*; D052638:Particulate Matter / Q000633:toxicity*; D013458:Sulfur Dioxide / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D019332:Endothelin-1; D015850:Interleukin-6; D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha; D013458:Sulfur Dioxide; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; D009585:Nitrogen Dioxide
keywords: air pollutant co-exposure; endothelial dysfunction; heart; inflammation