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.

Figure 1

Schematic of serum inflammatory potential assay. Primary human coronary artery endothelial cells were incubated with complete serum from study participants for 4 h, after which endothelial cell inflammatory responses were assessed by real time (RT)-qPCR for intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and chemokine ligand 2 (CCL2). Assays were performed in duplicate.

Figure 2

(a) Study area and heat map of area-weighted proximity to abandoned uranium mine (AUM) and mill sites. The Southeastern region of the Navajo Nation sits within the Northwestern portion of New Mexico and contains ~ 100 mine sites. (b) Distribution of Navajo participants’ household weighted proximities (based on linear distance and size of mine site) to AUM, with higher numbers reflecting a greater net exposure. (c) Distribution of Navajo participant residence linear distances (in km) from AUM.

Figure 3

Linear regression plots of weighted abandoned uranium mine (AUM) proximity associations with (a) chemokine ligand 2 (CCL2), (b) vascular cell adhesion molecule-1 (VCAM-1) and (c) intercellular adhesion molecule-1 (ICAM-1) mRNA from endothelial cell responses to participant serum.