title: MicroRNAs are associated with blood-pressure effects of exposure to particulate matter: Results from a mediated moderation analysis.
abstract: OBJECTIVE
  Exposure to particulate air pollution is associated with increased blood pressure (BP), a well-established risk factor for cardiovascular disease. To elucidate the mechanisms underlying this relationship, we investigated whether the effects of particulate matter of less than 10μm in aerodynamic diameter (PM10) on BP are mediated by microRNAs.
  
  
  RESULTS
  We recruited 90 obese individuals and we assessed their PM10 exposure 24 and 48h before the recruitment day. We performed multivariate linear regression models to investigate the effects of PM10 on BP. Using the TaqMan® Low-Density Array, we experimentally evaluated and technically validated the expression levels of 377 human miRNAs in peripheral blood. We developed a mediated moderation analysis to estimate the proportion of PM10 effects on BP that was mediated by miRNA expression. PM10 exposure 24 and 48h before the recruitment day was associated with increased systolic BP (β=1.22mmHg, P=0.019; β=1.24mmHg, P=0.019, respectively) and diastolic BP (β=0.67mmHg, P=0.044; β=0.91mmHg, P=0.007, respectively). We identified nine miRNAs associated with PM10 levels 48h after exposure. A conditional indirect effect (CIE=-0.1431) of PM10 on diastolic BP, which was mediated by microRNA-101, was found in individuals with lower values of mean body mass index.
  
  
  CONCLUSIONS
  Our data provide evidence that miRNAs are a molecular mechanism underlying the BP-related effects of air pollution exposure, and indicate miR-101 as epigenetic mechanism to be further investigated.
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy. Electronic address: valeria.motta@unimi.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Motta
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy. Electronic address: chiara.favero@unimi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Favero
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy. Electronic address: laura.dioni@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Dioni
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy. Electronic address: simona.iodice@unimi.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Iodice
authors.affiliation: Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20129 Milan, Italy. Electronic address: laura.angelici@unimi.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Battaglia
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy. Electronic address: laura.angelici@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Angelici
authors.affiliation: Worker's Health Protection and Promotion Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy. Electronic address: luisella.vigna@policlinico.mi.it.
authors.forename: Luisella
authors.initials: L
authors.lastname: Vigna
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy; Epidemiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy. Electronic address: angela.pesatori@unimi.it.
authors.forename: Angela Cecilia
authors.initials: AC
authors.lastname: Pesatori
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy. Electronic address: valentina.bollati@unimi.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects*; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000209:etiology; D050177:Overweight / Q000209:etiology; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D035683:MicroRNAs; D052638:Particulate Matter
keywords: Air pollution; Blood pressure; Cardiovascular disease; Microrna; Obesity