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.

Greater Odds for Angina in Uranium Miners Than Nonuranium Miners in New Mexico

“…Studies linking non-occupational uranium exposure to cardiovascular disease provide supportive evidence for our findings without establishing causality (41). A recent study highlighted the effects of inhalational environmental uranium exposure on cardiovascular disease outcomes among Navajo community members who live in close proximity to abandoned uranium mines in NM (41).…”

“…Studies linking non-occupational uranium exposure to cardiovascular disease provide supportive evidence for our findings without establishing causality (41). A recent study highlighted the effects of inhalational environmental uranium exposure on cardiovascular disease outcomes among Navajo community members who live in close proximity to abandoned uranium mines in NM (41). Primary human coronary artery endothelial cells treated for 4 hours with serum provided by Navajo study participants revealed that proximity to abandoned uranium mine strongly predicted endothelial transcriptional responses to serum cell adhesion molecules and chemokines (including CCL2, VCAM-1, and ICAM-1), suggesting inflammatory potential associated with residential proximity to abandoned uranium mines (41).…”

“…A recent study highlighted the effects of inhalational environmental uranium exposure on cardiovascular disease outcomes among Navajo community members who live in close proximity to abandoned uranium mines in NM (41). Primary human coronary artery endothelial cells treated for 4 hours with serum provided by Navajo study participants revealed that proximity to abandoned uranium mine strongly predicted endothelial transcriptional responses to serum cell adhesion molecules and chemokines (including CCL2, VCAM-1, and ICAM-1), suggesting inflammatory potential associated with residential proximity to abandoned uranium mines (41). The upregulation of these cell adhesion molecules and chemokines by endothelial cells has been shown to play a role in the multistep process leading to cardiovascular diseases (42).…”

“…Radiation specific mechanisms at low doses of exposure are as yet unclear, although there is evidence pointing to vascular structures and tissues of the heart as possible initiating targets (22). Basic research has shown that exposure to particulate matter during mining causes endothelial inflammation and dysfunction in both myocardial tissues and peripheral blood vessels, thus a mechanism to explain the increased of risk of hypertension and cardiovascular diseases in miners (41). An increased thickness of the intima in irradiated arteries and an increase in proteoglycan deposition in the media has been demonstrated (43).…”

Perspectives on Biological Monitoring in Environmental Health Research: A Focus Group Study in a Native American Community

“…The mined regions are contaminated with arsenic, copper, uranium, and other heavy metals as well as remaining radionuclides, representing an exposure risk to metals associated with adverse health and developmental effects [ 2 ]. Harmon et al (2017 and 2018) reported an association between arsenic and uranium from water intake and residential proximity to abandoned uranium mining sites with markers of pre-clinical cardiovascular effects [ 3 , 4 ]. In a recent review, Gonzales et al (2018) identified Native American and other rural populations in the Southwest, Mountain West, and adjacent regions of the U.S. to be at risk for sufficient exposure to environmental metals to result in elevated risks for numerous adverse health outcomes [ 5 ].…”