title: Residential proximity to abandoned uranium mines and serum inflammatory potential in chronically exposed Navajo communities.
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.
authors.affiliation: Department of Pharmaceutical Sciences, Albuquerque, NM, USA.
authors.forename: Molly E
authors.initials: ME
authors.lastname: Harmon
authors.affiliation: Community Environmental Health Program, College of Pharmacy, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Johnnye
authors.initials: J
authors.lastname: Lewis
authors.affiliation: Community Environmental Health Program, College of Pharmacy, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Miller
authors.affiliation: Community Environmental Health Program, College of Pharmacy, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hoover
authors.affiliation: Department of Earth and Planetary Sciences, UNM, Albuquerque, NM, USA.
authors.forename: Abdul-Mehdi S
authors.initials: AS
authors.lastname: Ali
authors.affiliation: Southwest Research and Information Center, Albuquerque, NM, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Shuey
authors.affiliation: Community Environmental Health Program, College of Pharmacy, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Miranda
authors.initials: M
authors.lastname: Cajero
authors.affiliation: Department of Pharmaceutical Sciences, Albuquerque, NM, USA.
authors.forename: Selita
authors.initials: S
authors.lastname: Lucas
authors.affiliation: Department of Pharmaceutical Sciences, Albuquerque, NM, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Zychowski
authors.affiliation: Community Environmental Health Program, College of Pharmacy, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pacheco
authors.affiliation: Community Environmental Health Program, College of Pharmacy, Department of Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Erdei
authors.affiliation: Southwest Research and Information Center, Albuquerque, NM, USA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Ramone
authors.affiliation: Southwest Research and Information Center, Albuquerque, NM, USA.
authors.forename: Teddy
authors.initials: T
authors.lastname: Nez
authors.affiliation: Division of Epidemiology, School of Medicine, UNM, Albuquerque, NM, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Gonzales
authors.affiliation: Department of Pharmaceutical Sciences, Albuquerque, NM, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Campen
mesh_terms: D000328:Adult; D000368:Aged; D001151:Arsenic / Q000009:adverse effects / Q000032:analysis; D001681:Biological Assay; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism*; D003331:Coronary Vessels; D060766:Drinking Water; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D040362:Geographic Information Systems; D006801:Humans; D007198:Indians, North American; D019570:Inhalation Exposure; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism*; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D008906:Mining; D012044:Regression Analysis; D014501:Uranium / Q000009:adverse effects* / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D060766:Drinking Water; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014501:Uranium; D001151:Arsenic