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Toxicol Appl Pharmacol

Title:		Environmental exposure to volatile organic compounds is associated with endothelial injury
Author(s):		Riggs DW; Malovichko MV; Gao H; McGraw KE; Taylor BS; Krivokhizhina T; Rai SN; Keith RJ; Bhatnagar A; Srivastava S;
Address:		"Superfund Research Center, University of Louisville, United States of America; Diabetes and Obesity Center, University of Louisville, United States of America; Christina Lee Brown Envirome Institute, University of Louisville, United States of America; Division of Environmental Medicine, Department of Medicine, University of Louisville, United States of America; Department of Epidemiology and Population Health, University of Louisville, United States of America. Superfund Research Center, University of Louisville, United States of America; Diabetes and Obesity Center, University of Louisville, United States of America; Christina Lee Brown Envirome Institute, University of Louisville, United States of America; Division of Environmental Medicine, Department of Medicine, University of Louisville, United States of America. Superfund Research Center, University of Louisville, United States of America; Diabetes and Obesity Center, University of Louisville, United States of America. Superfund Research Center, University of Louisville, United States of America; Diabetes and Obesity Center, University of Louisville, United States of America; Department of Bioinformatics and Biostatistics, University of Louisville, United States of America. Superfund Research Center, University of Louisville, United States of America; Diabetes and Obesity Center, University of Louisville, United States of America; Division of Environmental Medicine, Department of Medicine, University of Louisville, United States of America. Superfund Research Center, University of Louisville, United States of America; Diabetes and Obesity Center, University of Louisville, United States of America; Christina Lee Brown Envirome Institute, University of Louisville, United States of America; Division of Environmental Medicine, Department of Medicine, University of Louisville, United States of America. Electronic address: sanjay.srivastava@louisville.edu"
Journal Title:		Toxicol Appl Pharmacol
Year:		2022
Volume:		20220116
Issue:
Page Number:		115877 -
DOI:		10.1016/j.taap.2022.115877
ISSN/ISBN:		1096-0333 (Electronic) 0041-008X (Print) 0041-008X (Linking)
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:		"Adult Aged Air Pollutants/chemistry/*toxicity Biomarkers Endothelium, Vascular/*drug effects Environmental Exposure/*adverse effects Female Hazardous Substances Humans Male Middle Aged Molecular Structure Smoking Volatile Organic Compounds/chemistry/*toxi;"
Notes:		"MedlineRiggs, Daniel W Malovichko, Marina V Gao, Hong McGraw, Katlyn E Taylor, Breandon S Krivokhizhina, Tatiana Rai, Shesh N Keith, Rachel J Bhatnagar, Aruni Srivastava, Sanjay eng P50 HL120163/HL/NHLBI NIH HHS/ R01 ES029846/ES/NIEHS NIH HHS/ P42 ES023716/ES/NIEHS NIH HHS/ T32 ES011564/ES/NIEHS NIH HHS/ P30 GM127607/GM/NIGMS NIH HHS/ R01 ES019217/ES/NIEHS NIH HHS/ U54 HL120163/HL/NHLBI NIH HHS/ R01 HL149351/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2022/01/20 Toxicol Appl Pharmacol. 2022 Feb 15; 437:115877. doi: 10.1016/j.taap.2022.115877. Epub 2022 Jan 16"