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Metabolomics identifying biomarkers of PM2.5 exposure for vulnerable population: based on a prospective cohort study

Environmental Science and Pollution Research volume 28, pages 14586–14596 (2021)Cite this article

Abstract

Long-term exposure to particular matter (PM), especially fine PM (< 2.5 μm in the aerodynamic diameter, PM2.5), is associated with increased risk of cardiovascular disorders. This study aimed to evaluate the association between long-term exposure to PM2.5/PM10 and the metabolic change in the plasma. Specifically, using metabolomics, we sought to identify the biomarkers for the vulnerable subgroup to PM2.5 exposure. A total of 78 college student volunteers were recruited into this prospective cohort study. All participants received 8 rounds of physical examinations at twice quarterly. Air purifiers were placed in 40 of 78 participants’ dormitories for 14 days. Before and after intervention, physical examinations were performed and the peripheral blood was collected. Plasma metabolomics was determined by ultra-performance liquid chromatography-mass spectrometry. During the follow-up, the average concentrations of PM2.5 and PM10 were 53 μg/m3 and 93 μg/m3, respectively. Totally, 42 and 120 differential metabolic features were detected for PM10 and PM2.5 exposure, respectively. In total, 25 differential metabolites were identified for PM2.5 exposure, most of which were phospholipids. No distinctive metabolites were found for PM10 exposure. A total of 6 differential metabolites (lysoPC (P-20:0), lysoPC (P-18:1(9z)), lysoPC (20:1), lysoPC (O-16:0), choline, and found 1,3-diphenylprop-2-en-1-one) were characterized and confirmed for sensitive individuals. Importantly, we found LysoPC (P-20:0) and LysoPC (P-18:1(9z)) changed significantly before and after air purifier intervention. Our results indicated that the phospholipid catabolism was involved in long-term PM2.5 exposure. LysoPC (P-20:0) and LysoPC (P-18:1(9z)) may be the biomarkers of PM2.5 exposure.

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References

  • Adam M, Schikowski T, Carsin AE, Cai Y, Jacquemin B, Sanchez M, Vierkotter A, Marcon A, Keidel D, Sugiri D, Al Kanani Z, Nadif R, Siroux V, Hardy R, Kuh D, Rochat T, Bridevaux PO, Eeftens M, Tsai MY, Villani S, Phuleria HC, Birk M, Cyrys J, Cirach M, de Nazelle A, Nieuwenhuijsen MJ, Forsberg B, de Hoogh K, Declerq C, Bono R, Piccioni P, Quass U, Heinrich J, Jarvis D, Pin I, Beelen R, Hoek G, Brunekreef B, Schindler C, Sunyer J, Kramer U, Kauffmann F, Hansell AL, Kunzli N, Probst-Hensch N (2015) Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis. Eur Respir J 45:38–50

    CAS  Google Scholar 

  • Al-Hemoud A, Gasana J, Al-Dabbous AN, Al-Shatti A, Al-Khayat A (2018) Disability adjusted life years (DALYs) in terms of years of life lost (YLL) due to premature adult mortalities and postneonatal infant mortalities attributed to PM 2.5 and PM 10 exposures in Kuwait. Int J Environ Res Public Health 15(11):2609

    CAS  Google Scholar 

  • Al-Hemoud A, Gasana J, Al-Dabbous A, Alajeel A, Al-Shatti A, Behbehani W, Malak M (2019) Exposure levels of air pollution (PM 2.5) and associated health risk in Kuwait. Environ Res 179((Pt A):108730

    CAS  Google Scholar 

  • Anderson JO, Thundiyil JG, Stolbach A (2012) Clearing the air: a review of the effects of particulate matter air pollution on human health. J Med Toxicol 8:166–175

    CAS  Google Scholar 

  • Aoki J, Taira A, Takanezawa Y, Kishi Y, Hama K, Kishimoto T, Mizuno K, Saku K, Taguchi R, Arai H (2002) Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem 277:48737–48744

    CAS  Google Scholar 

  • Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC Jr, Whitsel L, Kaufman JD (2010) Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 121:2331–2378

    CAS  Google Scholar 

  • Chen W-L, Lin C-Y, Yan Y-H, Cheng KT, Cheng T-J (2014) Alterations in rat pulmonary phosphatidylcholines after chronic exposure to ambient fine particulate matter. Mol BioSyst 10(12):3163–3169

    CAS  Google Scholar 

  • Chen R, Zhao A, Chen H, Zhao Z, Cai J, Wang C, Yang C, Li H, Xu X, Ha S, Li T, Kan H (2015) Cardiopulmonary benefits of reducing indoor particles of outdoor origin: a randomized, double-blind crossover trial of air purifiers. J Am Coll Cardiol 65:2279–2287

    Google Scholar 

  • Chen Z, Salam MT, Toledo-Corral C, Watanabe RM, Xiang AH, Buchanan TA, Habre R, Bastain TM, Lurmann F, Wilson JP, Trigo E, Gilliland FD (2016) Ambient air pollutants have adverse effects on insulin and glucose homeostasis in Mexican Americans. Diabetes Care 39:547–554

    CAS  Google Scholar 

  • Chu H, Xin J, Yuan Q, Zhang X, Pan W, Zeng X, Chen Y, Ma G, Ge Y, Du M, Tong N, Li X, Zhang Z, Wang M (2018) Evaluation of vulnerable PM2.5-exposure individuals: a repeated-measure study in an elderly population. Environ Sci Pollut Res Int 25:11833–11840

    CAS  Google Scholar 

  • Di Q, Wang Y, Zanobetti A, Koutrakis P, Choirat C, Dominici F, Schwartz JD (2017) Air pollution and mortality in the medicare population. N Engl J Med 376:2513–2522

    CAS  Google Scholar 

  • Eckel SP, Louis TA, Chaves PH, Fried LP, Margolis AH (2012) Modification of the association between ambient air pollution and lung function by frailty status among older adults in the Cardiovascular Health Study. Am J Epidemiol 176:214–223

    Google Scholar 

  • Fan Y, Li Y, Chen Y, Zhao YJ, Liu LW, Li J, Wang SL, Alolga RN, Yin Y, Wang XM, Zhao DS, Shen JH, Meng FQ, Zhou X, Xu H, He GP, Lai MD, Li P, Zhu W, Qi LW (2016) Comprehensive metabolomic characterization of coronary artery diseases. J Am Coll Cardiol 68:1281–1293

    Google Scholar 

  • Fiehn O (2002) Metabolomics--the link between genotypes and phenotypes. Plant Mol Biol 48:155–171

    CAS  Google Scholar 

  • Floegel A, Stefan N, Yu Z, Muhlenbruch K, Drogan D, Joost HG, Fritsche A, Haring HU, Hrabe de Angelis M, Peters A, Roden M, Prehn C, Wang-Sattler R, Illig T, Schulze MB, Adamski J, Boeing H, Pischon T (2013) Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes 62:639–648

    CAS  Google Scholar 

  • Ge C, Tan J, Zhong S, Lai L, Chen G, Zhao J, Yi C, Wang L, Zhou L, Tang T, Yang Q, Lou D, Li Q, Wu Y, Hu L, Kuang G, Liu X, Wang B, Xu M (2020) Nrf2 mitigates prolonged PM2.5 exposure-triggered liver inflammation by positively regulating SIKE activity: protection by Juglanin. Redox Biol 36:101645

    CAS  Google Scholar 

  • Gehring U, Gruzieva O, Agius RM, Beelen R, Custovic A, Cyrys J, Eeftens M, Flexeder C, Fuertes E, Heinrich J, Hoffmann B, de Jongste JC, Kerkhof M, Klumper C, Korek M, Molter A, Schultz ES, Simpson A, Sugiri D, Svartengren M, von Berg A, Wijga AH, Pershagen G, Brunekreef B (2013) Air pollution exposure and lung function in children: the ESCAPE project. Environ Health Perspect 121:1357–1364

    Google Scholar 

  • Hosono H, Aoki J, Nagai Y, Bandoh K, Ishida M, Taguchi R, Arai H, Inoue K (2001) Phosphatidylserine-specific phospholipase A1 stimulates histamine release from rat peritoneal mast cells through production of 2-acyl-1-lysophosphatidylserine. J Biol Chem 276:29664–29670

    CAS  Google Scholar 

  • Johnson CH, Ivanisevic J, Siuzdak G (2016) Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol 17:451–459

    CAS  Google Scholar 

  • Knuplez E, Marsche G (2020) An updated review of pro- and anti-inflammatory properties of plasma lysophosphatidylcholines in the vascular system. Int J Mol Sci 21(12):4501

    CAS  Google Scholar 

  • Lelieveld J, Evans JS, Fnais M, Giannadaki D, Pozzer A (2015) The contribution of outdoor air pollution sources to premature mortality on a global scale. Nature 525:367–371

    CAS  Google Scholar 

  • Li Z, Vance DE (2008) Phosphatidylcholine and choline homeostasis. J Lipid Res 49:1187–1194

    CAS  Google Scholar 

  • Li H, Cai J, Chen R, Zhao Z, Ying Z, Wang L, Chen J, Hao K, Kinney PL, Chen H, Kan H (2017) Particulate matter exposure and stress hormone levels: a randomized, double-blind, crossover trial of air purification. Circulation 136:618–627

    CAS  Google Scholar 

  • Lin P, Ye RD (2003) The lysophospholipid receptor G2A activates a specific combination of G proteins and promotes apoptosis. J Biol Chem 278:14379–14386

    CAS  Google Scholar 

  • Liu P, Zhu W, Chen C, Yan B, Zhu L, Chen X, Peng C (2020) The mechanisms of lysophosphatidylcholine in the development of diseases. Life Sci 247:117443

    CAS  Google Scholar 

  • Murugesan G, Fox PL (1996) Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein. J Clin Invest 97:2736–2744

    CAS  Google Scholar 

  • Murugesan G, Chisolm GM, Fox PL (1993) Oxidized low density lipoprotein inhibits the migration of aortic endothelial cells in vitro. J Cell Biol 120:1011–1019

    CAS  Google Scholar 

  • Paoletti L, Elena C, Domizi P, Banchio C (2011) Role of phosphatidylcholine during neuronal differentiation. IUBMB Life 63:714–720

    CAS  Google Scholar 

  • Parker JD, Kravets N, Vaidyanathan A (2018) Particulate matter air pollution exposure and heart disease mortality risks by race and ethnicity in the United States: 1997 to 2009 national health interview survey with mortality follow-up through 2011. Circulation 137:1688–1697

    CAS  Google Scholar 

  • Patti GJ, Yanes O, Siuzdak G (2012) Innovation: metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol 13:263–269

    CAS  Google Scholar 

  • Paynter NP, Balasubramanian R, Giulianini F, Wang DD, Tinker LF, Gopal S, Deik AA, Bullock K, Pierce KA, Scott J, Martinez-Gonzalez MA, Estruch R, Manson JE, Cook NR, Albert CM, Clish CB, Rexrode KM (2018) Metabolic predictors of incident coronary heart disease in women. Circulation 137:841–853

    Google Scholar 

  • Pope CA 3rd, Turner MC, Burnett RT, Jerrett M, Gapstur SM, Diver WR, Krewski D, Brook RD (2015) Relationships between fine particulate air pollution, cardiometabolic disorders, and cardiovascular mortality. Circ Res 116:108–115

    CAS  Google Scholar 

  • Portman OW, Alexander M (1969) Lysophosphatidylcholine concentrations and metabolism in aortic intima plus inner media: effect of nutritionally induced atherosclerosis. J Lipid Res 10:158–165

    CAS  Google Scholar 

  • Radu CG, Yang LV, Riedinger M, Au M, Witte ON (2004) T cell chemotaxis to lysophosphatidylcholine through the G2A receptor. Proc Natl Acad Sci U S A 101:245–250

    CAS  Google Scholar 

  • Rao PN, Chen QH, Knaus EE (2005) Synthesis and biological evaluation of 1,3-diphenylprop-2-yn-1-ones as dual inhibitors of cyclooxygenases and lipoxygenases. Bioorg Med Chem Lett 15:4842–4845

    CAS  Google Scholar 

  • Vilahur G, Gutierrez M, Casani L, Varela L, Capdevila A, Pons-Llado G, Carreras F, Carlsson L, Hidalgo A, Badimon L (2016) Protective effects of ticagrelor on myocardial injury after infarction. Circulation 134:1708–1719

    CAS  Google Scholar 

  • Wang Z, Tang WH, Buffa JA, Fu X, Britt EB, Koeth RA, Levison BS, Fan Y, Wu Y, Hazen SL (2014) Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J 35:904–910

    CAS  Google Scholar 

  • Zarghi A, Arfaee S, Rao PN, Knaus EE (2006) Design, synthesis, and biological evaluation of 1,3-diarylprop-2-en-1-ones: a novel class of cyclooxygenase-2 inhibitors. Bioorg Med Chem 14:2600–2605

    CAS  Google Scholar 

  • Zeisel SH (2012) Dietary choline deficiency causes DNA strand breaks and alters epigenetic marks on DNA and histones. Mutat Res 733:34–38

    CAS  Google Scholar 

  • Zhang L, Wei TT, Li Y, Li J, Fan Y, Huang FQ, Cai YY, Ma G, Liu JF, Chen QQ, Wang SL, Li H, Alolga RN, Liu B, Zhao DS, Shen JH, Wang XM, Zhu W, Li P, Qi LW (2018) Functional metabolomics characterizes a key role for N-acetylneuraminic acid in coronary artery diseases. Circulation 137:1374–1390

    CAS  Google Scholar 

  • Zhang J, Liang S, Ning R, Jiang J, Zhang J, Shen H, Chen R, Duan J, Sun Z (2020) PM 2.5-induced inflammation and lipidome alteration associated with the development of atherosclerosis based on a targeted lipidomic analysis. Environ Int 136:105444

    CAS  Google Scholar 

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Funding

This study was partly supported by grants from the National Natural Science Foundation of China (81903390), Jiangsu Provincial Natural Science Foundation (BK20190555) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

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Author notes

  1. Haiyan Chu and Feng-Qing Huang contributed equally to this work.

Affiliations

  1. Department of Environmental Genomics, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, China

    Haiyan Chu, Qi Yuan, Junyi Xin, Mulong Du, Meilin Wang & Zhengdong Zhang

  2. Department of Genetic Toxicology, Center for Global Health, School of Public Health, Nanjing Medical Universty, Nanjing, China

    Haiyan Chu, Qi Yuan, Junyi Xin, Mulong Du, Meilin Wang & Zhengdong Zhang

  3. State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Road, Nanjing, 211198, China

    Feng-Qing Huang, Yuanming Fan & Gaoxiang Ma

Authors
  1. Haiyan Chu
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  2. Feng-Qing Huang
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  4. Yuanming Fan
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  8. Zhengdong Zhang
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  9. Gaoxiang Ma
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Contributions

ZD Z and GX M designed and supervised this study; HY C and GX M wrote this manuscript; Q Y and HY C collected the samples; FQ H performed this metabolomics analysis; JY X and YM F conducted the data analysis; ML W and ML D revised this manuscript.

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Correspondence to Zhengdong Zhang or Gaoxiang Ma.

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Participants provided written informed consent and the Nanjing Medical University Review Board approved the study.

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Chu, H., Huang, FQ., Yuan, Q. et al. Metabolomics identifying biomarkers of PM2.5 exposure for vulnerable population: based on a prospective cohort study. Environ Sci Pollut Res 28, 14586–14596 (2021). https://doi.org/10.1007/s11356-020-11677-0

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  • DOI: https://doi.org/10.1007/s11356-020-11677-0

Keywords

  • PM2.5
  • Plasma metabolomics
  • Vulnerable subgroup screening
  • Biomarkers