Original Article | Published:

Fine particles, genetic pathways, and markers of inflammation and endothelial dysfunction: Analysis on particulate species and sources

Journal of Exposure Science and Environmental Epidemiology volume 26, pages 415421 (2016) | Download Citation

Abstract

Studies have found associations between PM2.5 and cardiovascular events. The role of different components of PM2.5 is not well understood. We used linear mixed-effects models with the adaptive LASSO penalty to select PM2.5 species and source(s), separately, that may be associated with markers of inflammation and endothelial dysfunction, with adjustment for age, obesity, smoking, statin use, diabetes mellitus, temperature, and season as fixed effects in a large longitudinal cohort of elderly men. We also analyzed these associations with source apportionment models and examined genetic pathway–air pollution interactions within three relevant pathways (oxidative stress, metal processing, and endothelial function). We found that independent of PM2.5 mass vanadium (V) was associated with intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). An IQR increase (3.2 ng/m3) in 2-day moving average V was associated with a 2.5% (95% CI: 1.2–3.8%) change in ICAM-1 and a 3.9% (95% CI: 2.2–5.7%) change in VCAM-1, respectively. In addition, an oil combustion source rich in V was linked to these adhesion molecules. People with higher allelic risk profiles related to oxidative stress may have greater associations (P-value of interaction=0.11). Our findings suggest that particles derived from oil combustion may be associated with inflammation and endothelial dysfunction, and it is likely that oxidative stress plays a role in the associations.

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References

  1. 1.

    , , , , , et al. Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 2004; 109: 2655–2671.

  2. 2.

    , , , , , et al. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 2010; 121: 2331–2378.

  3. 3.

    , , , , , et al. Air pollution and markers of inflammation and coagulation in patients with coronary heart disease. Am J Respir Crit Care Med 2006; 173: 432–441.

  4. 4.

    , , , . Sulfate content correlates with iron concentrations in ambient air pollution particles. Inhal Toxicol 1999; 11: 293–307.

  5. 5.

    , , , , , et al. Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation. Environ Health Perspect 2009; 117: 217–222.

  6. 6.

    , , . The Normative Aging Study: an interdisciplinary and longitudinal study of health and aging. Aging Hum Dev 1972; 3: 4–17.

  7. 7.

    , , . Hourly measurements of fine particulate sulfate and carbon aerosols at the Harvard-U.S. Environmental Protection Agency Supersite in Boston. J Air Waste Manag Assoc 2010; 60: 1327–1334.

  8. 8.

    , . Source apportionment of ambient particles in steubenville, OH using specific rotation factor analysis. Atmo Env (1967) 1987; 21: 1511–1519.

  9. 9.

    , , , , , . Use of the adaptive LASSO method to identify PM components associated with blood pressure in elderly men: the Veterans Affairs Normative Aging Study. Environ Health Perspect 2015 e-pub ahead of print 20 June 2015 doi:10.1289/ehp.1409021.

  10. 10.

    . Regression shrinkage and selection via the Lasso. J R Stat Soc Series B Methodol 1996; 58: 267–288.

  11. 11.

    . The adaptive Lasso and its oracle properties. J Am Stat Assoc 2006; 101: 1418–1429.

  12. 12.

    . Estimating the dimension of a model. The Ann Stat 1978; 6: 461–464.

  13. 13.

    , , , , , et al. Air pollution, obesity, genes and cellular adhesion molecules. Occup Environ Med 2010; 67: 312–317.

  14. 14.

    , , , , , et al. Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)). Am J Respir Crit Care Med 2001; 164: 826–830.

  15. 15.

    , , , , , et al. Recent exposure to particulate matter and C-reactive protein concentration in the multi-ethnic study of atherosclerosis. Am J Epidemiol 2006; 164: 437–448.

  16. 16.

    , , , , . Inflammatory markers and particulate air pollution: characterizing the pathway to disease. Int J Epidemiol 2006; 35: 1347–1354.

  17. 17.

    , , , , , et al. Modeling the association between particle constituents of air pollution and health outcomes. Am J Epidemiol 2012; 176: 317–326.

  18. 18.

    , , , , , et al. A novel genetic score approach using instruments to investigate interactions between pathways and environment: application to air pollution. PLoS One 2014; 9: e96000.

  19. 19.

    , , , , , et al. GeneCards Version 3: the human gene integrator. Database 2010; 2010: baq020.

  20. 20.

    , , , , , et al. Circulating cell adhesion molecules and death in patients with coronary artery disease. Circulation 2001; 104: 1336–1342.

  21. 21.

    , , , , , et al. Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: the PRIME Study. Atherosclerosis 2003; 170: 169–176.

  22. 22.

    , , . Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men. Circulation 2002; 106: 820–825.

  23. 23.

    , , , , , et al. Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility. Occup Environ Med 2007; 64: 373–379.

  24. 24.

    , , , , , et al. Air pollution and markers of coagulation, inflammation, and endothelial function: associations and epigene-environment interactions in an elderly cohort. Epidemiology 2012; 23: 332–340.

  25. 25.

    , , , , , et al. Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers. Am J Respir Crit Care Med 1999; 159: 702–709.

  26. 26.

    , , , , , et al. Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel. Eur Respir J 2004; 23: 82–86.

  27. 27.

    , , , , , et al. Medium-term exposure to traffic-related air pollution and markers of inflammation and endothelial function. Environ Health Perspect 2011; 119: 481–486.

  28. 28.

    , , , , , et al. Cardiovascular and thermoregulatory effects of inhaled PM-associated transition metals: a potential interaction between nickel and vanadium sulfate. Toxicol Sci 2001; 64: 243–252.

  29. 29.

    , , , , , et al. The role of particulate matter-associated zinc in cardiac injury in rats. Environ Health Perspect 2008; 116: 13–20.

  30. 30.

    , , , , . Cardiovascular effects of nickel in ambient air. Environ Health Perspect 2006; 114: 1662–1669.

  31. 31.

    , , , , , . Vanadium pentoxide induces activation and death of endothelial cells. J Appl Toxicol 2012; 32: 26–33.

  32. 32.

    , , , , , et al. Nickel-regulated heart rate variability: the roles of oxidative stress and inflammation. Toxicol Appl Pharmacol 2013; 266: 298–306.

  33. 33.

    , , , . Endothelial effects of emission source particles: acute toxic response gene expression profiles. Toxicol In Vitro 2009; 23: 67–77.

  34. 34.

    , , , . Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. Eur Heart J 2000; 21: 1574–1583.

  35. 35.

    , , , , , et al. Air pollution and inflammation (interleukin-6, C-reactive protein, fibrinogen) in myocardial infarction survivors. Environ Health Perspect 2007; 115: 1072–1080.

  36. 36.

    , , , , , et al. Particulate air pollution is associated with an acute phase response in men; results from the MONICA-Augsburg Study. Eur Heart J 2001; 22: 1198–1204.

  37. 37.

    , , , , , et al. Ambient particulate air pollution, heart rate variability, and blood markers of inflammation in a panel of elderly subjects. Environ Health Perspect 2004; 112: 339–345.

  38. 38.

    , , , , , et al. Air pollution exposures and circulating biomarkers of effect in a susceptible population: clues to potential causal component mixtures and mechanisms. Environ Health Perspect 2009; 117: 1232–1238.

  39. 39.

    , , , , , et al. Traffic-related exposures and biomarkers of systemic inflammation, endothelial activation and oxidative stress: a panel study in the US trucking industry. Environ Health 2013; 12: 1–10.

  40. 40.

    , , , . Biologic effects of oil fly ash. Environ Health Perspect 2002; 110 (Suppl 1): 89–94.

  41. 41.

    National Research CouncilResearch Priorities for Airborne Particulate Matter: IV. Continuing Research Progress. National Research Council: Washington, DC. 2004.

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Acknowledgements

This study was supported by the National Institute of Environmental Health Sciences Grants ES00002 and ES015172-01, and the US Environmental Protection Agency Grant RD-834798-01. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the funders. Furthermore, the funders do not endorse the purchase of any commercial products or services mentioned in the publication. Dr. David Sparrow was supported by a VA Research Career Scientist award. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Centers of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts.

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Affiliations

  1. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

    • Lingzhen Dai
    • , Marie-Abele Bind
    • , Petros Koutrakis
    •  & Joel D Schwartz
  2. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

    • Brent A Coull
  3. Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston Massachusetts, USA

    • David Sparrow
    •  & Pantel S Vokonas

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The authors declare no conflict of interest.

Corresponding author

Correspondence to Lingzhen Dai.

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DOI

https://doi.org/10.1038/jes.2015.83

Supplementary Information accompanies the paper on the Journal of Exposure Science and Environmental Epidemiology website (http://www.nature.com/jes)

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