Environmental exposure to volatile organic compounds is associated with endothelial injury

Abstract

Objective: Volatile organic compounds (VOCs) are airborne toxicants abundant in outdoor and indoor air. High levels of VOCs are also present at various Superfund and other hazardous waste sites; however, little is known about the cardiovascular effects of VOCs. We hypothesized that ambient exposure to VOCs exacerbate cardiovascular disease (CVD) risk by depleting circulating angiogenic cells (CACs).

Approach and results: In this cross-sectional study, we recruited 603 participants with low-to-high CVD risk and measured 15 subpopulations of CACs by flow cytometry and 16 urinary metabolites of 12 VOCs by LC/MS/MS. Associations between CAC and VOC metabolite levels were examined using generalized linear models in the total sample, and separately in non-smokers. In single pollutant models, metabolites of ethylbenzene/styrene and xylene, were negatively associated with CAC levels in both the total sample, and in non-smokers. The metabolite of acrylonitrile was negatively associated with CD45^dim/CD146⁺/CD34⁺/AC133⁺ cells and CD45⁺/CD146⁺/AC133⁺, and the toluene metabolite with AC133⁺ cells. In analysis of non-smokers (n = 375), multipollutant models showed a negative association with metabolites of ethylbenzene/styrene, benzene, and xylene with CD45^dim/CD146⁺/CD34⁺ cells, independent of other VOC metabolite levels. Cumulative VOC risk score showed a strong negative association with CD45^dim/CD146⁺/CD34⁺ cells, suggesting that total VOC exposure has a cumulative effect on pro-angiogenic cells. We found a non-linear relationship for benzene, which showed an increase in CAC levels at low, but depletion at higher levels of exposure. Sex and race, hypertension, and diabetes significantly modified VOC associated CAC depletion.

Conclusion: Low-level ambient exposure to VOCs is associated with CAC depletion, which could compromise endothelial repair and angiogenesis, and exacerbate CVD risk.

Keywords: Benzene; Circulating angiogenic cells; Endothelial injury; Ethylbenzene; VOCs; Volatile organic compounds.