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Vehicular Particulate Matter (PM) Characteristics Impact Vascular Outcomes Following Inhalation

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Abstract

Roadside proximity and exposure to mixed vehicular emissions (MVE) have been linked to adverse pulmonary and vascular outcomes. However, because of the complex nature of the contribution of particulate matter (PM) versus gases, it is difficult to decipher the precise causative factors regarding PM and the copollutant gaseous fraction. To this end, C57BL/6 and apolipoprotein E knockout mice (ApoE−/−) were exposed to either filtered air (FA), fine particulate (FP), FP+gases (FP+G), ultrafine particulate (UFP), or UFP+gases (UFP+G). Two different timeframes were employed: 1-day (acute) or 30-day (subchronic) exposures. Examined biological endpoints included aortic vasoreactivity, aortic lesion quantification, and aortic mRNA expression. Impairments in vasorelaxation were observed following acute exposure to FP+G in C57BL/6 animals and FP, UFP, and UFP+G in ApoE−/− animals. These effects were completely abrogated or markedly reduced following subchronic exposure. Aortic lesion quantification in ApoE−/− animals indicated a significant increase in atheroma size in the UFP-, FP-, and FP+G-exposed groups. Additionally, ApoE−/− mice demonstrated a significant fold increase in TNFα expression following FP+G exposure and ET-1 following UFP exposure. Interestingly, C57BL/6 aortic gene expression varied widely across exposure groups. TNFα decreased significantly following FP exposure and CCL-5 decreased in the UFP-, FP-, and FP+G-exposed groups. Conversely, ET-1, CCL-2, and CXCL-1 were all significantly upregulated in the FP+G group. These findings suggest that gas–particle interactions may play a role in vascular toxicity, but the contribution of surface area is not clear.

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References

  1. Hoffmann, B., et al. (2007). Residential exposure to traffic is associated with coronary atherosclerosis. Circulation,116(5), 489–496.

    CAS  PubMed  Google Scholar 

  2. Mills, N. L., et al. (2009). Adverse cardiovascular effects of air pollution. Nature Clinical Practice Cardiovascular Medicine,6(1), 36–44.

    CAS  PubMed  Google Scholar 

  3. Pope, C. A., 3rd, et al. (2011). Vascular function and short-term exposure to fine particulate air pollution. Journal of the Air and Waste Management Association,61(8), 858–863.

    CAS  PubMed  Google Scholar 

  4. Ruidavets, J. B., et al. (2005). Ozone air pollution is associated with acute myocardial infarction. Circulation,111(5), 563–569.

    CAS  PubMed  Google Scholar 

  5. Wellenius, G. A., et al. (2012). Ambient air pollution and the risk of acute ischemic stroke. Archives of Internal Medicine,172(3), 229–234.

    PubMed  PubMed Central  Google Scholar 

  6. Maynard, A. D. A. E. D. K. (2005). Airborne nanostructured particles and occupational health. Journal of Nanoparticle Research,7(6), 587–614.

    CAS  Google Scholar 

  7. Schwarze, P. E., et al. (2006). Particulate matter properties and health effects: consistency of epidemiological and toxicological studies. Human and Experimental Toxicology,25(10), 559–579.

    CAS  PubMed  Google Scholar 

  8. Dockery, D. W., et al. (1993). An association between air pollution and mortality in six U.S. cities. The New England Journal of Medicine,329(24), 1753–1759.

    CAS  PubMed  Google Scholar 

  9. Vedal, S., et al. (2013). National Particle Component Toxicity (NPACT) initiative report on cardiovascular effects. Research Report/Health Effects Institute,178, 5–8.

    Google Scholar 

  10. Campen, M., et al. (2014). Engine exhaust particulate and gas phase contributions to vascular toxicity. Inhalation Toxicology,26(6), 353–360.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Tyler, C. R., et al. (2016). Surface area-dependence of gas-particle interactions influences pulmonary and neuroinflammatory outcomes. Particle and Fibre Toxicology,13(1), 64.

    PubMed  PubMed Central  Google Scholar 

  12. Bai, N., et al. (2011). Changes in atherosclerotic plaques induced by inhalation of diesel exhaust. Atherosclerosis,216(2), 299–306.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Campen, M. J., et al. (2010). Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE(−/−) mice. Toxicology and Applied Pharmacology,242(3), 310–317.

    CAS  PubMed  Google Scholar 

  14. Hansen, C. S., et al. (2007). Diesel exhaust particles induce endothelial dysfunction in apoE−/− mice. Toxicology and Applied Pharmacology,219(1), 24–32.

    CAS  PubMed  Google Scholar 

  15. Hazari, M. S., et al. (2011). TRPA1 and sympathetic activation contribute to increased risk of triggered cardiac arrhythmias in hypertensive rats exposed to diesel exhaust. Environmental Health Perspectives,119(7), 951–957.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Quan, C., et al. (2010). Comparative effects of inhaled diesel exhaust and ambient fine particles on inflammation, atherosclerosis, and vascular dysfunction. Inhalation Toxicology,22(9), 738–753.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Miller, M. R., et al. (2013). Diesel exhaust particulate increases the size and complexity of lesions in atherosclerotic mice. Particle and Fibre Toxicology,10, 61.

    PubMed  PubMed Central  Google Scholar 

  18. Araujo, J. A., et al. (2008). Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress. Circulation Research,102(5), 589–596.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Sun, Q., et al. (2005). Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. JAMA,294(23), 3003–3010.

    CAS  PubMed  Google Scholar 

  20. Lund, A. K., et al. (2007). Gasoline exhaust emissions induce vascular remodeling pathways involved in atherosclerosis. Toxicological Sciences,95(2), 485–494.

    CAS  PubMed  Google Scholar 

  21. Bisig, C., et al. (2018). Assessment of lung cell toxicity of various gasoline engine exhausts using a versatile in vitro exposure system. Environmental Pollution,235, 263–271.

    CAS  PubMed  Google Scholar 

  22. Lund, A. K., et al. (2011). The oxidized low-density lipoprotein receptor mediates vascular effects of inhaled vehicle emissions. American Journal of Respiratory and Critical Care Medicine,184(1), 82–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Lennox Siwale, L. K., Adam, T., Bereczky, A., Mbarawa, M., Penninger, A., & Kolesnikov, A. (2013). Combustion and emission characteristics of n-butanol/diesel fuel blend in a turbo-charged compression ignition engine. Fuel,107, 409–418.

    Google Scholar 

  24. Frank Ruiz, M. C., Lopez, A., Sanchez-Valdepenas, J., & Agudelo, J. R. (2015). Impact of dual-fuel combustion with n-butanol or hydrous ethanol on the oxidation reactivity and nanostructure of diesel particulate matter. Fuel,161, 18–25.

    Google Scholar 

  25. Cheung, C. S., Zhu, L., & Huang, Z. (2009). Regulated and unregulated emissions from a diesel engine fueled with biodiesel and biodiesel blended with methanol. Atmospheric Environment,43(32), 4865–4872.

    CAS  Google Scholar 

  26. de Brito, J. M., et al. (2018). Acute exposure to diesel and sewage biodiesel exhaust causes pulmonary and systemic inflammation in mice. Science of the Total Environment,628–629, 1223–1233.

    PubMed  Google Scholar 

  27. Cassee, F. R., et al. (2012). The biological effects of subacute inhalation of diesel exhaust following addition of cerium oxide nanoparticles in atherosclerosis-prone mice. Environmental Research,115, 1–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang, J., et al. (2013). Impacts of a nanosized ceria additive on diesel engine emissions of particulate and gaseous pollutants. Environmental Science and Technology,47(22), 13077–13085.

    CAS  PubMed  Google Scholar 

  29. Snow, S. J., et al. (2014). Inhaled diesel emissions generated with cerium oxide nanoparticle fuel additive induce adverse pulmonary and systemic effects. Toxicological Sciences,142(2), 403–417.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. McDonald, J. D., et al. (2004). Generation and characterization of four dilutions of diesel engine exhaust for a subchronic inhalation study. Environmental Science and Technology,38(9), 2513–2522.

    CAS  PubMed  Google Scholar 

  31. McDonald, J. D., et al. (2008). Generation and characterization of gasoline engine exhaust inhalation exposure atmospheres. Inhalation Toxicology,20(13), 1157–1168.

    CAS  PubMed  Google Scholar 

  32. Herring, C. L., Faiola, C. L., Massoli, P., Sueper, D., Erickson, M. H., McDonald, J. D., et al. (2015). New methodology for quantifying polycyclic aromatic hydrocarbons (PAHs) using high-resolution aerosol mass spectrometry. Aerosol Science and Technology,49(11), 1131–1148.

    CAS  Google Scholar 

  33. Aragon, M., et al. (2016). MMP-9-dependent serum-borne bioactivity caused by multiwalled carbon nanotube exposure induces vascular dysfunction via the CD36 Scavenger receptor. Toxicological Sciences,150(2), 488–498.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Aragon, M. J., et al. (2016). Inflammatory and vasoactive effects of serum following inhalation of varied complex mixtures. Cardiovascular Toxicology,16(2), 163–171.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Brook, R. D., et al. (2010). Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation,121(21), 2331–2378.

    CAS  PubMed  Google Scholar 

  36. Pope, C. A., 3rd. (2007). Mortality effects of longer term exposures to fine particulate air pollution: review of recent epidemiological evidence. Inhalation Toxicology,19(Suppl 1), 33–38.

    CAS  PubMed  Google Scholar 

  37. Pope, C. A., 3rd, et al. (2004). Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation,109(1), 71–77.

    PubMed  Google Scholar 

  38. Hoffmann, B., et al. (2009). Chronic residential exposure to particulate matter air pollution and systemic inflammatory markers. Environmental Health Perspectives,117(8), 1302–1308.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Tonne, C., et al. (2007). A case-control analysis of exposure to traffic and acute myocardial infarction. Environmental Health Perspectives,115(1), 53–57.

    CAS  PubMed  Google Scholar 

  40. Van Hee, V. C., et al. (2009). Exposure to traffic and left ventricular mass and function: The Multi-Ethnic Study of Atherosclerosis. American Journal of Respiratory and Critical Care Medicine,179(9), 827–834.

    PubMed  PubMed Central  Google Scholar 

  41. Sioutas, C., Delfino, R. J., & Singh, M. (2005). Exposure assessment for atmospheric ultrafine particles (UFPs) and implications in epidemiologic research. Environmental Health Perspectives,113(8), 947–955.

    PubMed  PubMed Central  Google Scholar 

  42. Wichmann, H. E., et al. (2000). Daily mortality and fine and ultrafine particles in Erfurt, Germany part I: role of particle number and particle mass. Research Reports: Health Effects Institute,2000(98), 5–86. discussion 87–94.

    Google Scholar 

  43. Tong, H., et al. (2010). Differential cardiopulmonary effects of size-fractionated ambient particulate matter in mice. Cardiovascular Toxicology,10(4), 259–267.

    CAS  PubMed  Google Scholar 

  44. Channell, M. M., et al. (2012). Circulating factors induce coronary endothelial cell activation following exposure to inhaled diesel exhaust and nitrogen dioxide in humans: evidence from a novel translational in vitro model. Toxicological Sciences,127(1), 179–186.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Robertson, S., et al. (2013). CD36 mediates endothelial dysfunction downstream of circulating factors induced by O3 exposure. Toxicological Sciences,134(2), 304–311.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Mostovenko, E., et al. (2019). Nanoparticle exposure driven circulating bioactive peptidome causes systemic inflammation and vascular dysfunction. Particle and Fibre Toxicology,16(1), 20.

    PubMed  PubMed Central  Google Scholar 

  47. Campen, M. J., Lund, A., & Rosenfeld, M. (2012). Mechanisms linking traffic-related air pollution and atherosclerosis. Current Opinion in Pulmonary Medicine,18(2), 155–160.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Cherng, T. W., et al. (2009). Impairment of coronary endothelial cell ET(B) receptor function after short-term inhalation exposure to whole diesel emissions. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology,297(3), R640–R647.

    CAS  PubMed  Google Scholar 

  49. Kodavanti, U. P., et al. (2011). Vascular and cardiac impairments in rats inhaling ozone and diesel exhaust particles. Environmental Health Perspectives,119(3), 312–318.

    CAS  PubMed  Google Scholar 

  50. Plump, A. S., et al. (1992). Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell,71(2), 343–353.

    CAS  PubMed  Google Scholar 

  51. Zhang, S. H., et al. (1992). Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science,258(5081), 468–471.

    CAS  PubMed  Google Scholar 

  52. Rao, X., et al. (2014). CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure. Circulation Research,115(9), 770–780.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Oberdorster, G. (2001). Pulmonary effects of inhaled ultrafine particles. International Archives of Occupational and Environmental Health,74(1), 1–8.

    CAS  PubMed  Google Scholar 

  54. Sarnat, J. A., et al. (2008). Fine particle sources and cardiorespiratory morbidity: An application of chemical mass balance and factor analytical source-apportionment methods. Environmental Health Perspectives,116(4), 459–466.

    PubMed  PubMed Central  Google Scholar 

  55. Lund, A. K., et al. (2009). Vehicular emissions induce vascular MMP-9 expression and activity associated with endothelin-1-mediated pathways. Arteriosclerosis, Thrombosis, and Vascular Biology,29(4), 511–517.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Lund, A. K., et al. (2013). The effects of alpha-pinene versus toluene-derived secondary organic aerosol exposure on the expression of markers associated with vascular disease. Inhalation Toxicology,25(6), 309–324.

    CAS  PubMed  Google Scholar 

  57. Kobayashi, T., et al. (2000). Corresponding distributions of increased endothelin-B receptor expression and increased endothelin-1 expression in the aorta of apolipoprotein E-deficient mice with advanced atherosclerosis. Pathology International,50(12), 929–936.

    CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Jesse Denson for manuscript editing and assistance in preparation.

Funding

This work has been supported by the ASERT-IRACDA program at UNM (K12GM088021) and NIEHS (K99ES029104; R01 ES014639).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, The University of New Mexico, College of Pharmacy, Albuquerque, NM, USA

    Katherine E. Zychowski, Bethany Sanchez, Molly Harmon & Matthew J. Campen

  2. Biosciences Division, Los Alamos National Laboratories, Los Alamos, NM, USA

    Christina R. Steadman Tyler

  3. Lovelace Respiratory Research Institute, Albuquerque, NM, USA

    June Liu, Hammad Irshad & Jacob D. McDonald

  4. Department of Pharmacy Practice & Administrative Sciences, The University of New Mexico, College of Pharmacy, Albuquerque, NM, USA

    Barry E. Bleske

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  1. Katherine E. Zychowski
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Correspondence to Katherine E. Zychowski.

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Zychowski, K.E., Tyler, C.R.S., Sanchez, B. et al. Vehicular Particulate Matter (PM) Characteristics Impact Vascular Outcomes Following Inhalation. Cardiovasc Toxicol 20, 211–221 (2020). https://doi.org/10.1007/s12012-019-09546-5

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