Extracellular vesicle-packaged miRNA release after short-term exposure to particulate matter is associated with increased coagulation

Particle and Fibre Toxicology

Vincenza Dolo¹  Cristina Battaglia²  Andrea Cattaneo³  Marilena Letizia⁴  Mirjam Hoxha⁴  Pier Alberto Bertazzi⁴  Angela Cecilia Pesatori⁴  Michele Carugno⁴  Chiara Favero⁴  Benedetta Albetti⁴  Laura Pergoli⁴  Valentina Bollati⁴  Laura Angelici⁴  Matteo Bonzini⁴  Letizia Tarantini⁴  Laura Cantone⁴  Laura Dioni⁴  Simona Iodice⁵  Federica Rota⁵  Luisella Vigna⁵  Amedea Silvia Tirelli⁵  Eva Pinatel⁶ 

[1] Department of Life, Health and Environmental Sciences, University of L’Aquila;Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano;Department of Science and High Technology, University of Insubria;EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano;Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Unit of Occupational Medicine;Institute for Biomedical Technologies (ITB), National Research Council (CNR);

关键词: Air pollution;    Extracellular vesicles;    microRNAs;    Fibrinogen;    Cardiovascular disease;   

DOI  :  10.1186/s12989-017-0214-4

来源: DOAJ

【 摘 要 】

Abstract Background Exposure to particulate matter (PM) is associated with increased incidence of cardiovascular disease and increased coagulation, but the molecular mechanisms underlying these associations remain unknown. Obesity may increase susceptibility to the adverse effects of PM exposure, exacerbating the effects on cardiovascular diseases. Extracellular vesicles (EVs), which travel in body fluids and transfer microRNAs (miRNAs) between tissues, might play an important role in PM-induced cardiovascular risk. We sought to determine whether the levels of PM with an aerodynamic diameter ≤ 10 μm (PM10) are associated with changes in fibrinogen levels, EV release, and the miRNA content of EVs (EV-miRNAs), investigating 1630 overweight/obese subjects from the SPHERE Study. Results Short-term exposure to PM10 (Day before blood drawing) was associated with an increased release of EVs quantified by nanoparticle tracking analysis, especially EVs derived from monocyte/macrophage components (CD14+) and platelets (CD61+) which were characterized by flow cytometry. We first profiled miRNAs of 883 subjects by the QuantStudio™ 12 K Flex Real Time PCR System and the top 40 EV-miRNAs were validated through custom miRNA plates. Nine EV-miRNAs (let-7c-5p; miR-106a-5p; miR-143-3p; miR-185-5p; miR-218-5p; miR-331-3p; miR-642-5p; miR-652-3p; miR-99b-5p) were downregulated in response to PM10 exposure and exhibited putative roles in cardiovascular disease, as highlighted by integrated network analysis. PM10 exposure was significantly associated with elevated fibrinogen levels, and five of the nine downregulated EV-miRNAs were mediators between PM10 exposure and fibrinogen levels. Conclusions Research on EVs opens a new path to the investigation of the adverse health effects of air pollution exposure. EVs have the potential to act both as markers of PM susceptibility and as potential molecular mechanism in the chain of events connecting PM exposure to increased coagulation, which is frequently linked to exposure and CVD development.

【 授权许可】

Unknown