Abstract
Members of the Navajo Nation, who possess a high prevalence of cardiometabolic disease, reside near hundreds of local abandoned uranium mines (AUM), which contribute uranium, arsenic and other metals to the soil, water and air. We recently reported that hypertension is associated with mine waste exposures in this population. Inflammation is a major player in the development of numerous vascular ailments. Our previous work establishing that specific transcriptional responses of cultured endothelial cells treated with human serum can reveal relative circulating inflammatory potential in a manner responsive to pollutant exposures, providing a model to assess responses associated with exposure to these waste materials in this population. To investigate a potential link between exposures to AUM and serum inflammatory potential in affected communities, primary human coronary artery endothelial cells were treated for 4 h with serum provided by Navajo study participants (n=145). Endothelial transcriptional responses of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and chemokine ligand 2 (CCL2) were measured. These transcriptional responses were then linked to AUM exposure metrics, including surface area-weighted AUM proximity and estimated oral intake of metals. AUM proximity strongly predicted endothelial transcriptional responses to serum including CCL2, VCAM-1 and ICAM-1 (P<0.0001 for each), whereas annual water intakes of arsenic and uranium did not, even after controlling for all major effect modifiers. Inflammatory potential associated with proximity to AUMs, but not oral intake of specific metals, additionally suggests a role for inhalation exposure as a contributor to cardiovascular disease.
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Acknowledgements
This research was supported by the National Institute of Environmental Health Sciences (NIEHS P30 ES-012072, R25 ES013208, R01 ES014639 & R01 ES014565), the National Heart, Lung and Blood Institute (NHLBI T32 HL007736), the National Institute for General Medical Sciences (GM088021), the University of New Mexico General Clinical Research Center (NIH NCRR GCRC Grant # M01-RR00997), the UNM HSC Clinical & Translational Science Center (NIH NCATS Grant # 8UL1TR000041), and in-kind water analyses from USEPA Region IX Laboratories. We would like to thank Deborah MacKenzie for her technical assistance. The authors wish to sincerely thank all of the Navajo chapter members who participated in this study.
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Harmon, M., Lewis, J., Miller, C. et al. Residential proximity to abandoned uranium mines and serum inflammatory potential in chronically exposed Navajo communities. J Expo Sci Environ Epidemiol 27, 365–371 (2017). https://doi.org/10.1038/jes.2016.79
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DOI: https://doi.org/10.1038/jes.2016.79
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