Oxidative stress and inflammation mediate the effect of air pollution on cardio- and cerebrovascular disease: A prospective study in nonsmokers

被引:88
作者
Fiorito, Giovanni [1 ,2 ]
Vlaanderen, Jelle [3 ]
Polidoro, Silvia [1 ]
Gulliver, John [4 ]
Galassi, Claudia [5 ,6 ]
Ranzi, Andrea [7 ]
Krogh, Vittorio [8 ]
Grioni, Sara [8 ]
Agnoli, Claudia [8 ]
Sacerdote, Carlotta [5 ,6 ]
Panico, Salvatore [9 ]
Tsai, Ming-Yi [10 ,11 ]
Probst-Hensch, Nicole [10 ,11 ]
Hoek, Gerard [3 ]
Herceg, Zdenko [12 ]
Vermeulen, Roel [3 ]
Ghantous, Akram [12 ]
Vineis, Paolo [1 ,4 ]
Naccarati, Alessio [1 ]
机构
[1] Italian Inst Genom Med, Via Nizza 52, Turin, Italy
[2] Univ Turin, Dept Med Sci, Turin, Italy
[3] Univ Utrecht, Inst Risk Assessment Sci, Environm Epidemiol Div, Utrecht, Netherlands
[4] Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England
[5] Scienza Univ Hosp, Citta Salute & Sci, Unit Canc Epidemiol, Turin, Italy
[6] Ctr Canc Prevent CPO, Turin, Italy
[7] Reg Agcy Prevent Environm & Energy Emilia Romagna, Environm Hlth Reference Ctr, Modena, Italy
[8] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy
[9] Univ Naples Federico II, Dipartimento Med Clin & Chirurg, Naples, Italy
[10] Univ Basel, Basel, Switzerland
[11] Swiss Trop & Publ Hlth Inst, Basel, Switzerland
[12] Int Agcy Res Canc, Lyon, France
关键词
air pollution; oxidative stress; inflammation; cytokine signaling; cardiovascular diseases; cerebrovascular diseases; USE REGRESSION-MODELS; LONG-TERM EXPOSURE; DNA-METHYLATION; ENVIRONMENTAL STRESSORS; CARDIOVASCULAR-DISEASE; F2RL3; METHYLATION; ADULT ASTHMA; SMOKING; RISK; CANCER;
D O I
10.1002/em.22153
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Air pollution is associated with a broad range of adverse health effects, including mortality and morbidity due to cardio- and cerebrovascular diseases (CCVD), but the molecular mechanisms involved are not entirely understood. This study aims to investigate the involvement of oxidative stress and inflammation in the causal chain, and to identify intermediate biomarkers that are associated retrospectively with the exposure and prospectively with the disease. We designed a case-control study on CCVD nested in a cohort of 18,982 individuals from the EPIC-Italy study. We measured air pollution, inflammatory biomarkers, and whole-genome DNA methylation in blood collected up to 17 years before the diagnosis. The study sample includes all the incident CCVD cases among former- and never-smokers, with available stored blood sample, that arose in the cohort during the follow-up. We identified enrichment of altered DNA methylation in ROS/Glutathione/Cytotoxic granules and Cytokine signaling pathways related genes, associated with both air pollution (multiple comparisons adjusted p for enrichment ranging from 0.01 to 0.03 depending on pollutant) and with CCVD risk (P=0.04 and P=0.03, respectively). Also, Interleukin-17 was associated with higher exposure to NO2 (P=0.0004), NOx (P=0.0005), and CCVD risk (OR=1.79; CI 1.04-3.11; P=0.04 comparing extreme tertiles). Our findings indicate that chronic exposure to air pollution can lead to oxidative stress, which in turn activates a cascade of inflammatory responses mainly involving the Cytokine signaling pathway, leading to increased risk of CCVD. Inflammatory proteins and DNA methylation alterations can be detected several years before CCVD diagnosis in blood samples, being promising preclinical biomarkers. Environ. Mol. Mutagen. 59:234-246, 2018. (c) 2017 Wiley Periodicals, Inc.
引用
收藏
页码:234 / 246
页数:13
相关论文
共 81 条
[1]   Particulate Matter Air Pollution and Cardiovascular Disease An Update to the Scientific Statement From the American Heart Association [J].
Brook, Robert D. ;
Rajagopalan, Sanjay ;
Pope, C. Arden, III ;
Brook, Jeffrey R. ;
Bhatnagar, Aruni ;
Diez-Roux, Ana V. ;
Holguin, Fernando ;
Hong, Yuling ;
Luepker, Russell V. ;
Mittleman, Murray A. ;
Peters, Annette ;
Siscovick, David ;
Smith, Sidney C., Jr. ;
Whitsel, Laurie ;
Kaufman, Joel D. .
CIRCULATION, 2010, 121 (21) :2331-2378
[2]   Novel Epigenetic Changes Unveiled by Monozygotic Twins Discordant for Smoking Habits [J].
Allione, Alessandra ;
Marcon, Francesca ;
Fiorito, Giovanni ;
Guarrera, Simonetta ;
Siniscalchi, Ester ;
Zijno, Andrea ;
Crebelli, Riccardo ;
Matullo, Giuseppe .
PLOS ONE, 2015, 10 (06)
[3]   Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays [J].
Aryee, Martin J. ;
Jaffe, Andrew E. ;
Corrada-Bravo, Hector ;
Ladd-Acosta, Christine ;
Feinberg, Andrew P. ;
Hansen, Kasper D. ;
Irizarry, Rafael A. .
BIOINFORMATICS, 2014, 30 (10) :1363-1369
[4]  
Baccarelli A, 2010, EPIGENETICS-US, V5
[5]   Development of NO2 and NOx land use regression models for estimating air pollution exposure in 36 study areas in Europe - The ESCAPE project [J].
Beelen, Rob ;
Hoek, Gerard ;
Vienneau, Danielle ;
Eeftens, Marloes ;
Dimakopoulou, Konstantina ;
Pedeli, Xanthi ;
Tsai, Ming-Yi ;
Kunzli, Nino ;
Schikowski, Tamara ;
Marcon, Alessandro ;
Eriksen, Kirsten T. ;
Raaschou-Nielsen, Ole ;
Stephanou, Euripides ;
Patelarou, Evridiki ;
Lanki, Timo ;
Yli-Tuomi, Tarja ;
Declercq, Christophe ;
Falq, Gregoire ;
Stempfelet, Morgane ;
Birk, Matthias ;
Cyrys, Josef ;
von Klot, Stephanie ;
Nador, Gizella ;
Varro, Mihaly Janos ;
Dedele, Audrius ;
Grazuleviciene, Regina ;
Moelter, Anna ;
Lindley, Sarah ;
Madsen, Christian ;
Cesaroni, Giulia ;
Ranzi, Andrea ;
Badaloni, Chiara ;
Hoffmann, Barbara ;
Nonnemacher, Michael ;
Kraemer, Ursula ;
Kuhlbusch, Thomas ;
Cirach, Marta ;
de Nazelle, Audrey ;
Nieuwenhuijsen, Mark ;
Bellander, Tom ;
Korek, Michal ;
Olsson, David ;
Stromgren, Magnus ;
Dons, Evi ;
Jerrett, Michael ;
Fischer, Paul ;
Wang, Meng ;
Brunekreef, Bert ;
de Hoogh, Kees .
ATMOSPHERIC ENVIRONMENT, 2013, 72 :10-23
[6]   Predictors of cardiovascular disease in asthma and chronic obstructive pulmonary disease [J].
Bellocchia, Michela ;
Masoero, Monica ;
Ciuffreda, Antonio ;
Croce, Silvia ;
Vaudano, Arianna ;
Torchio, Roberto ;
Boita, Monica ;
Bucca, Caterina .
MULTIDISCIPLINARY RESPIRATORY MEDICINE, 2013, 8
[7]   Fruit, vegetables, and olive oil and risk of coronary heart disease in Italian women: the EPICOR Study [J].
Bendinelli, Benedetta ;
Masala, Giovanna ;
Saieva, Calogero ;
Salvini, Simonetta ;
Calonico, Carmela ;
Sacerdote, Carlotta ;
Agnoli, Claudia ;
Grioni, Sara ;
Frasca, Graziella ;
Mattiello, Amalia ;
Chiodini, Paolo ;
Tumino, Rosario ;
Vineis, Paolo ;
Palli, Domenico ;
Panico, Salvatore .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2011, 93 (02) :275-283
[8]   Smoking, F2RL3 methylation, and prognosis in stable coronary heart disease [J].
Breitling, Lutz Philipp ;
Salzmann, Katrin ;
Rothenbacher, Dietrich ;
Burwinkel, Barbara ;
Brenner, Hermann .
EUROPEAN HEART JOURNAL, 2012, 33 (22) :2841-2848
[9]   Effects of Air Pollution and Blood Mitochondrial DNA Methylation on Markers of Heart Rate Variability [J].
Byun, Hyang-Min ;
Colicino, Elena ;
Trevisi, Letizia ;
Fan, Tianteng ;
Christiani, David C. ;
Baccarelli, Andrea A. .
JOURNAL OF THE AMERICAN HEART ASSOCIATION, 2016, 5 (04)
[10]   Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project [J].
Cesaroni, Giulia ;
Forastiere, Francesco ;
Stafoggia, Massimo ;
Andersen, Zorana J. ;
Badaloni, Chiara ;
Beelen, Rob ;
Caracciolo, Barbara ;
de Faire, Ulf ;
Erbel, Raimund ;
Eriksen, Kirsten T. ;
Fratiglioni, Laura ;
Galassi, Claudia ;
Hampel, Regina ;
Heier, Margit ;
Hennig, Frauke ;
Hilding, Agneta ;
Hoffmann, Barbara ;
Houthuijs, Danny ;
Joeckel, Karl-Heinz ;
Korek, Michal ;
Lanki, Timo ;
Leander, Karin ;
Magnusson, Patrik K. E. ;
Migliore, Enrica ;
Ostenson, Caes-Goeran ;
Overvad, Kim ;
Pedersen, Nancy L. ;
Pekkanen, Juha J. ;
Penell, Johanna ;
Pershagen, Goeran ;
Pyko, Andrei ;
Raaschou-Nielsen, Ole ;
Ranzi, Andrea ;
Ricceri, Fulvio ;
Sacerdote, Carlotta ;
Salomaa, Veikko ;
Swart, Wim ;
Turunen, Anu W. ;
Vineis, Paolo ;
Weinmayr, Gudrun ;
Wolf, Kathrin ;
de Hoogh, Kees ;
Hoek, Gerard ;
Brunekreef, Bert ;
Peters, Annette .
BMJ-BRITISH MEDICAL JOURNAL, 2014, 348