Environmental Exposure to Volatile Organic Compounds is Associated with Endothelial Injury

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 375 non-smokers 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. Our data show that VOC exposure varied by sex, age, and race. In single pollutant models, metabolites of xylene, benzene, and 1,3-butadiene were negatively associated with CAC levels. The metabolite of acrylonitrile was negatively associated with CD45dim/CD146+/CD34+/AC133+ cells and CD45+/CD146+/AC133+, and the toluene metabolite with AC133+ cells. Multipollutant models showed a negative association with metabolites of ethylbenzene/styrene, benzene, and xylene with CD45dim/CD146+/CD34+ cells, independent of other VOC metabolite levels. Cumulative VOC risk score showed a strong negative association with CD45dim/CD146+/CD34+ cells, suggesting that total VOC exposure has a cumulative effect on pro-angiogenic cells. Dose-response relationship showed an increase in CAC levels at low, but depletion at higher levels of VOC 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.

[1]  Y. Wan,et al.  Repeated measurements of 21 urinary metabolites of volatile organic compounds and their associations with three selected oxidative stress biomarkers in 0-7-year-old healthy children from south and central China. , 2021, Chemosphere.

[2]  W. Xia,et al.  Urinary metabolites of multiple volatile organic compounds among general population in Wuhan, central China: Inter-day reproducibility, seasonal difference, and their associations with oxidative stress biomarkers. , 2021, Environmental pollution.

[3]  P. Lorkiewicz,et al.  Exposure to Volatile Organic Compounds - Acrolein, 1,3-Butadiene, and Crotonaldehyde - is Associated with Vascular Dysfunction. , 2021, Environmental research.

[4]  A. Hyland,et al.  Urinary Biomarkers of Exposure to Volatile Organic Compounds from the Population Assessment of Tobacco and Health Study Wave 1 (2013–2014) , 2020, International journal of environmental research and public health.

[5]  P. Lorkiewicz,et al.  Acute and chronic vascular effects of inhaled crotonaldehyde in mice: Role of TRPA1. , 2020, Toxicology and applied pharmacology.

[6]  P. Lorkiewicz,et al.  Association between residential greenness and exposure to volatile organic compounds. , 2019, The Science of the total environment.

[7]  D. Riggs,et al.  National secular trends in ambient air volatile organic compound levels and biomarkers of exposure in the United States. , 2019, Environmental research.

[8]  P. Lorkiewicz,et al.  Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco. , 2019, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[9]  B. Blount,et al.  Ethylbenzene and styrene exposure in the United States based on urinary mandelic acid and phenylglyoxylic acid: NHANES 2005–2006 and 2011–2012 , 2019, Environmental research.

[10]  P. Lorkiewicz,et al.  Formaldehyde Induces Mesenteric Artery Relaxation via a Sensitive Transient Receptor Potential Ankyrin-1 (TRPA1) and Endothelium-Dependent Mechanism: Potential Role in Postprandial Hyperemia , 2019, Front. Physiol..

[11]  P. Lorkiewicz,et al.  Characterization of Volatile Organic Compound (VOC) metabolites in Cigarette smokers, Electronic Nicotine Device Users, Dual Users and Non- users of tobacco. , 2019, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[12]  Dongmug Kang,et al.  Association between Heavy Metals, Bisphenol A, Volatile Organic Compounds and Phthalates and Metabolic Syndrome , 2019, International journal of environmental research and public health.

[13]  T. Zeng,et al.  The deleterious effects of N,N-dimethylformamide on liver: A mini-review. , 2019, Chemico-biological interactions.

[14]  P. Lorkiewicz,et al.  Association Between Residential Greenness and Cardiovascular Disease Risk , 2018, Journal of the American Heart Association.

[15]  A. Bhatnagar,et al.  Benzene Exposure Induces Insulin Resistance in Mice , 2018, Toxicological sciences : an official journal of the Society of Toxicology.

[16]  S. Rai,et al.  Circulating angiogenic stem cells in type 2 diabetes are associated with glycemic control and endothelial dysfunction , 2018, PloS one.

[17]  Sadeer G. Al-Kindi,et al.  Air Pollution and Cardiovascular Disease: JACC State-of-the-Art Review. , 2018, Journal of the American College of Cardiology.

[18]  L. Tian,et al.  Are ambient volatile organic compounds environmental stressors for heart failure? , 2018, Environmental pollution.

[19]  Jennifer F. Bobb,et al.  Statistical software for analyzing the health effects of multiple concurrent exposures via Bayesian kernel machine regression , 2018, Environmental Health.

[20]  J. Ran,et al.  Short-term effects of ambient benzene and TEX (toluene, ethylbenzene, and xylene combined) on cardiorespiratory mortality in Hong Kong. , 2018, Environment international.

[21]  A. Quyyumi,et al.  Circulating Progenitor Cells and Racial Differences: A Possible Contribution to Health Disparity , 2018, Circulation research.

[22]  Venecio Ultra,et al.  Health risk assessment of volatile organic compounds exposure near Daegu dyeing industrial complex in South Korea , 2018, BMC Public Health.

[23]  Guang-Hui Dong,et al.  Global association between ambient air pollution and blood pressure: A systematic review and meta-analysis. , 2018, Environmental pollution.

[24]  S. Rai,et al.  Benzene exposure is associated with cardiovascular disease risk , 2017, PloS one.

[25]  Yu Zhan,et al.  Combined effects of temperature and humidity on indoor VOCs pollution: Intercity comparison , 2017 .

[26]  P. Lorkiewicz,et al.  Biomarkers of Chronic Acrolein Inhalation Exposure in Mice: Implications for Tobacco Product-Induced Toxicity , 2017, Toxicological sciences : an official journal of the Society of Toxicology.

[27]  Matthew L. Thomas,et al.  Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015 , 2017, The Lancet.

[28]  Howard H. Chang,et al.  Estimating Acute Cardiorespiratory Effects of Ambient Volatile Organic Compounds , 2017, Epidemiology.

[29]  S. Rai,et al.  Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells , 2015, Arteriosclerosis, thrombosis, and vascular biology.

[30]  B. Coull,et al.  Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. , 2015, Biostatistics.

[31]  David E Newby,et al.  Short term exposure to air pollution and stroke: systematic review and meta-analysis , 2015, BMJ : British Medical Journal.

[32]  S. Rai,et al.  Acrolein Exposure Is Associated With Increased Cardiovascular Disease Risk , 2014, Journal of the American Heart Association.

[33]  Bhramar Mukherjee,et al.  Environmental Risk Score as a New Tool to Examine Multi-Pollutants in Epidemiologic Research: An Example from the NHANES Study Using Serum Lipid Levels , 2014, PloS one.

[34]  D. Pisetsky,et al.  The Effects of Smoking on Levels of Endothelial Progenitor Cells and Microparticles in the Blood of Healthy Volunteers , 2014, PloS one.

[35]  J. Schwartz,et al.  Brachial Artery Responses to Ambient Pollution, Temperature, and Humidity in People with Type 2 Diabetes: A Repeated-Measures Study , 2014, Environmental health perspectives.

[36]  R. Burnett,et al.  A cohort study of intra-urban variations in volatile organic compounds and mortality, Toronto, Canada. , 2013, Environmental pollution.

[37]  Brent A. Coull,et al.  Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures , 2013 .

[38]  R. Brook,et al.  The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study , 2013, Inhalation toxicology.

[39]  S. Feng,et al.  Evaluation of spot urine as an alternative to 24h urine collection for determination of biomarkers of exposure to cigarette smoke in adult smokers. , 2013, Environmental toxicology and pharmacology.

[40]  Sanjay Rajagopalan,et al.  Air Pollution and Type 2 Diabetes , 2012, Diabetes.

[41]  K. Alwis,et al.  Simultaneous analysis of 28 urinary VOC metabolites using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS). , 2012, Analytica chimica acta.

[42]  Kamonnaree Chotinantakul,et al.  Hematopoietic Stem Cell Development, Niches, and Signaling Pathways , 2012, Bone marrow research.

[43]  X. Zhang,et al.  Age-Related Decline in Reendothelialization Capacity of Human Endothelial Progenitor Cells Is Restored by Shear Stress , 2012, Hypertension.

[44]  A. Bhatnagar,et al.  Exposure to Ambient Air Fine Particulate Matter Prevents VEGF-Induced Mobilization of Endothelial Progenitor Cells from the Bone Marrow , 2012, Environmental health perspectives.

[45]  Eloi Marijon,et al.  Main air pollutants and myocardial infarction: a systematic review and meta-analysis. , 2012, JAMA.

[46]  B. Chandrasekar,et al.  Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy. , 2011, American journal of physiology. Heart and circulatory physiology.

[47]  A. Bhatnagar,et al.  Oral exposure to acrolein exacerbates atherosclerosis in apoE-null mice. , 2011, Atherosclerosis.

[48]  Lung-Chi Chen,et al.  Exposure to inhaled nickel nanoparticles causes a reduction in number and function of bone marrow endothelial progenitor cells , 2010, Inhalation toxicology.

[49]  D. Riggs,et al.  Exposure to acrolein by inhalation causes platelet activation. , 2010, Toxicology and applied pharmacology.

[50]  C. A. Pope,et al.  Episodic Exposure to Fine Particulate Air Pollution Decreases Circulating Levels of Endothelial Progenitor Cells , 2010, Circulation research.

[51]  T. Lüscher,et al.  Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension: Relation to Endothelial Dysfunction , 2010, Hypertension.

[52]  R. Brook,et al.  Particulate Matter Air Pollution and Cardiovascular Disease: An Update to the Scientific Statement From the American Heart Association , 2010, Circulation.

[53]  P. Juvan,et al.  Acrolein consumption induces systemic dyslipidemia and lipoprotein modification. , 2010, Toxicology and applied pharmacology.

[54]  M. Wolzt,et al.  Reduction of both number and proliferative activity of human endothelial progenitor cells in obesity , 2010, International Journal of Obesity.

[55]  E. Talbott,et al.  Association between Exposure to Alkylbenzenes and Cardiovascular Disease among National Health and Nutrition Examination Survey (NHANES) Participants , 2009, International journal of occupational and environmental health.

[56]  Nobel C. Zong,et al.  Acrolein consumption exacerbates myocardial ischemic injury and blocks nitric oxide-induced PKCepsilon signaling and cardioprotection. , 2008, Journal of molecular and cellular cardiology.

[57]  A. Avogaro,et al.  Gender Differences in Endothelial Progenitor Cells and Cardiovascular Risk Profile: The Role of Female Estrogens , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[58]  Thomas Sandström,et al.  Persistent endothelial dysfunction in humans after diesel exhaust inhalation. , 2007, American journal of respiratory and critical care medicine.

[59]  A. Penn,et al.  1,3-Butadiene exposure and cardiovascular disease. , 2007, Mutation research.

[60]  E. Samoli,et al.  Seasonal confounding in air pollution and health time‐series studies: effect on air pollution effect estimates , 2006, Statistics in medicine.

[61]  A. Bhatnagar,et al.  Acrolein induces vasodilatation of rodent mesenteric bed via an EDHF-dependent mechanism. , 2006, Toxicology and applied pharmacology.

[62]  G. Lip,et al.  Circulating endothelial cells in cardiovascular disease. , 2006, Journal of the American College of Cardiology.

[63]  GeorgNickenig,et al.  Influence of Cardiovascular Risk Factors on Endothelial Progenitor Cells , 2006 .

[64]  G. Nickenig,et al.  Influence of cardiovascular risk factors on endothelial progenitor cells: limitations for therapy? , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[65]  T. Imanishi,et al.  Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension , 2005, Journal of hypertension.

[66]  G. Nickenig,et al.  Circulating endothelial progenitor cells and cardiovascular outcomes. , 2005, The New England journal of medicine.

[67]  G. Matanoski,et al.  Styrene exposure and ischemic heart disease: a case-cohort study. , 2003, American journal of epidemiology.

[68]  Roger Atkinson,et al.  Atmospheric degradation of volatile organic compounds. , 2003, Chemical reviews.

[69]  A. Quyyumi,et al.  Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. , 2003, The New England journal of medicine.

[70]  S. Fichtlscherer,et al.  Number and Migratory Activity of Circulating Endothelial Progenitor Cells Inversely Correlate With Risk Factors for Coronary Artery Disease , 2001, Circulation research.

[71]  Michael Pittilo.  Cigarette smoking, endothelial injury and cardiovascular disease , 2000, International journal of experimental pathology.

[72]  G. Watts,et al.  Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. , 2000, The American journal of clinical nutrition.

[73]  G. Eisenbrand,et al.  Estimation of human exposure to styrene and ethylbenzene. , 2000, Toxicology.

[74]  M. Olschewski,et al.  Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL. , 1996, Circulation.

[75]  K. Kannan,et al.  A review of environmental occurrence, toxicity, biotransformation and biomonitoring of volatile organic compounds , 2021 .

[76]  Turner,et al.  Long-Term Fine Particulate Matter Exposure and Mortality From Diabetes Mellitus in Canada , 2013 .

[77]  A. Avogaro,et al.  Significance of Endothelial Progenitor Cells in Subjects with Diabetes Mellitus , 2007 .

[78]  D. Riggs,et al.  Residential Proximity to Major Roadways Is Associated With Increased Levels of AC 133 + Circulating Angiogenic Cells , 2022 .