TY - JOUR
T1 - Oxidative stress and inflammation mediate the effect of air pollution on cardio- and cerebrovascular disease
T2 - A prospective study in nonsmokers
AU - Fiorito, Giovanni
AU - Vlaanderen, Jelle
AU - Polidoro, Silvia
AU - Gulliver, John
AU - Galassi, Claudia
AU - Ranzi, Andrea
AU - Krogh, Vittorio
AU - Grioni, Sara
AU - Agnoli, Claudia
AU - Sacerdote, Carlotta
AU - Panico, Salvatore
AU - Tsai, Ming-Yi
AU - Probst-Hensch, Nicole
AU - Hoek, Gerard
AU - Herceg, Zdenko
AU - Vermeulen, Roel
AU - Ghantous, Akram
AU - Vineis, Paolo
AU - Naccarati, Alessio
AU - EXPOsOMICS consortium‡
N1 - © 2017 Wiley Periodicals, Inc.
PY - 2018/4
Y1 - 2018/4
N2 - 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., 2017. © 2017 Wiley Periodicals, Inc.
AB - 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., 2017. © 2017 Wiley Periodicals, Inc.
KW - air pollution
KW - oxidative stress
KW - inflammation
KW - cytokine signaling
KW - cardiovascular diseases
KW - cerebrovascular diseases
U2 - 10.1002/em.22153
DO - 10.1002/em.22153
M3 - Article
C2 - 29114965
SN - 0893-6692
VL - 59
SP - 234
EP - 246
JO - Environmental and Molecular Mutagenesis
JF - Environmental and Molecular Mutagenesis
IS - 3
ER -