title: Extracellular vesicle-driven information mediates the long-term effects of particulate matter exposure on coagulation and inflammation pathways.
abstract: BACKGROUND
  Continuous exposure to particulate air pollution (PM) is a serious worldwide threat to public health as it coherently links with increased morbidity and mortality of cardiorespiratory diseases (CRD), and of type 2 diabetes (T2D). Extracellular vesicles (EVs) are circular plasma membrane fragments released from human cells that transfer microRNAs between tissues. In the present work it was explored the hypothesis that EVs with their encapsulated microRNAs (EVmiRNAs) contents might mediate PM effects by triggering key pathways in CRD and T2D.
  
  
  METHODS
  Expression of EVmiRNAs analyzed by real-time PCR was correlated with oxidative stress, coagulation and inflammation markers, from healthy steel plant workers (n=55) with a well-characterized exposure to PM and PM-associated metals. All p-values were adjusted for multiple comparisons. In-silico Ingenuity Pathway Analysis (IPA) was performed to identify biological pathways regulated by PM-associated EVmiRNAs.
  
  
  RESULTS
  Increased expression in 17 EVmiRNAs is associated with PM and metal exposure (p<0.01). Mir-196b that tops the list, being related to 9 different metals, is fundamental in insulin biosynthesis, however three (miR-302b, miR-200c, miR-30d) out of these 17 EVmiRNAs are in turn also related to disruptions (p<0.01) in inflammatory and coagulation markers.
  
  
  CONCLUSIONS
  The study's findings support the hypothesis that adverse cardiovascular and metabolic effects stemming from inhalation exposures in particular to PM metallic component may be mediated by EVmiRNAs that target key factors in the inflammation, coagulation and glucose homeostasis pathways.
authors: Occupational Medicine, Department of Cardiac, Thoracic and Vascular Sciences, Università degli Studi di Padova, 35128, Padova, Italy. Electronic address: sofia.pavanello@unipd.it.
authors: Sofia
authors: S
authors: Pavanello
authors: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Epidemiology Unit, Department of Preventive Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors: Matteo
authors: M
authors: Bonzini
authors: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors: Laura
authors: L
authors: Angelici
authors: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors: Valeria
authors: V
authors: Motta
authors: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors: Laura
authors: L
authors: Pergoli
authors: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors: Mirjam
authors: M
authors: Hoxha
authors: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors: Laura
authors: L
authors: Cantone
authors: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Epidemiology Unit, Department of Preventive Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors: Angela Cecilia
authors: AC
authors: Pesatori
authors: Occupational Medicine and Industrial Hygiene, University of Brescia, Department of Experimental and Applied Medicine, Brescia, 25123, Italy.
authors: Pietro
authors: P
authors: Apostoli
authors: Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Department of Clinical Sciences and Community Health, Università degli Studi di Milano and IRCCS Maggiore Hospital Foundation, Milan, 20122, Italy.
authors: Armando
authors: A
authors: Tripodi
authors: Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY 10032, USA.
authors: Andrea
authors: A
authors: Baccarelli
authors: EPIGET - Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Epidemiology Unit, Department of Preventive Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors: Valentina
authors: V
authors: Bollati
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D000067128:Extracellular Vesicles / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D007962:Leukocytes; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D016273:Occupational Exposure; D052638:Particulate Matter / Q000633:toxicity*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D052638:Particulate Matter
keywords: Cardiorespiratory diseases (CRD); Coagulation; EV-encapsulated microRNAs (EVmiRNAs); Extracellular vesicles (EVs); Inflammation; Particulate air pollution (PM); Type 2 diabetes (T2D); microRNAs