title: Microvesicle-associated microRNA expression is altered upon particulate matter exposure in healthy workers and in A549 cells.
abstract: Cardiovascular disease risk has been consistently linked with particulate matter (PM) exposure. Cell-derived microvesicles (MVs) are released into plasma and transfer microRNAs (miRNAs) between tissues. MVs can be produced by the respiratory system in response to proinflammatory triggers, enter the circulatory system and remotely modify gene expression in cardiovascular tissues. However, whether PM affects MV signaling has never been investigated. In this study, we evaluated expression of microRNAs contained within plasma MVs upon PM exposure both in vivo and in vitro. In the in vivo study, we isolated plasma MVs from healthy steel plant workers before and after workplace PM exposure. We measured the expression of 88 MV-associated miRNAs by real-time polymerase chain reaction. To assess a possible source of the MV miRNAs identified in vivo, we measured their miRNA expression in PM-treated A549 pulmonary cell lines in vitro. MiRNA profiling of plasma MVs showed 5.62- and 13.95-fold increased expression of miR-128 and miR-302c, respectively, after 3 days of workplace PM exposure (P < 0.001). According to Ingenuity Pathway Analysis, miR-128 is part of coronary artery disease pathways, and miR-302c is part of coronary artery disease, cardiac hypertrophy and heart failure pathways. In vitro experiments confirmed a dose-dependent expression of miR-128 in MVs released from A549 cells after 6 h of PM treatment (P = 0.030). MiR-302c was expressed neither from A549 cells nor in reference lung RNA. These results suggest novel PM-activated molecular mechanisms that may mediate the effects of air pollution and could lead to the identification of new diagnostic and therapeutic interventions.
authors: Center of Molecular and Genetic Epidemiology, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Epidemiology Unit, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors: Valentina
authors: V
authors: Bollati
authors: Laura
authors: L
authors: Angelici
authors: Giovanna
authors: G
authors: Rizzo
authors: Laura
authors: L
authors: Pergoli
authors: Federica
authors: F
authors: Rota
authors: Mirjam
authors: M
authors: Hoxha
authors: Francesco
authors: F
authors: Nordio
authors: Matteo
authors: M
authors: Bonzini
authors: Letizia
authors: L
authors: Tarantini
authors: Laura
authors: L
authors: Cantone
authors: Angela C
authors: AC
authors: Pesatori
authors: Pietro
authors: P
authors: Apostoli
authors: Andrea A
authors: AA
authors: Baccarelli
authors: Pier Alberto
authors: PA
authors: Bertazzi
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008669:Metallurgy; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D052638:Particulate Matter / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000395:Air Pollutants, Occupational; C545189:MIRN128 microRNA, human; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; D052638:Particulate Matter
keywords: A549 cells; Particulate matter; microRNAs; microvesicles; steel plant workers