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

Fiorito, Giovanni and Vlaanderen, Jelle and Polidoro, Silvia and Gulliver, John and Galassi, Claudia and Ranzi, Andrea and Krogh, Vittorio and Grioni, Sara and Agnoli, Claudia and Sacerdote, Carlotta and Panico, Salvatore and Tsai, Ming-Yi and Probst-Hensch, Nicole and Hoek, Gerard and Herceg, Zdenko and Vermeulen, Roel and Ghantous, Akram and Vineis, Paolo and Naccarati, Alessio and ExposOmics consortium‡, . (2018) Oxidative stress and inflammation mediate the effect of air pollution on cardio- and cerebrovascular disease : a prospective study in nonsmokers. Environmental and molecular mutagenesis, 59 (3). pp. 234-246.

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Official URL: https://edoc.unibas.ch/64881/

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Abstract

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 NO; 2; (P = 0.0004), NO; x; (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. © 2017 Wiley Periodicals, Inc.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Tsai, Ming-Yi and Probst-Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1098-2280
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:04 Jul 2018 08:51
Deposited On:04 Jul 2018 08:51

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