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Extracellular vesicle-packaged miRNA release after short-term exposure to particulate matter is associated with increased coagulation.
Part Fibre Toxicol. 2017 08 24; 14(1):32.PF

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.

Authors+Show Affiliations

EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Occupational Medicine, Milan, Italy.Institute for Biomedical Technologies (ITB), National Research Council (CNR), Segrate, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Occupational Medicine, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Occupational Medicine, Milan, Italy.Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Occupational Medicine, Milan, Italy.Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.Department of Science and High Technology, University of Insubria, Como, Italy.Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Occupational Medicine, Milan, Italy.Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20129, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Occupational Medicine, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Occupational Medicine, Milan, Italy.EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via san Barnaba 8, 20122, Milan, Italy. valentina.bollati@unimi.it. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Occupational Medicine, Milan, Italy. valentina.bollati@unimi.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28899404

Citation

Pergoli, Laura, et al. "Extracellular Vesicle-packaged miRNA Release After Short-term Exposure to Particulate Matter Is Associated With Increased Coagulation." Particle and Fibre Toxicology, vol. 14, no. 1, 2017, p. 32.
Pergoli L, Cantone L, Favero C, et al. Extracellular vesicle-packaged miRNA release after short-term exposure to particulate matter is associated with increased coagulation. Part Fibre Toxicol. 2017;14(1):32.
Pergoli, L., Cantone, L., Favero, C., Angelici, L., Iodice, S., Pinatel, E., Hoxha, M., Dioni, L., Letizia, M., Albetti, B., Tarantini, L., Rota, F., Bertazzi, P. A., Tirelli, A. S., Dolo, V., Cattaneo, A., Vigna, L., Battaglia, C., Carugno, M., ... Bollati, V. (2017). Extracellular vesicle-packaged miRNA release after short-term exposure to particulate matter is associated with increased coagulation. Particle and Fibre Toxicology, 14(1), 32. https://doi.org/10.1186/s12989-017-0214-4
Pergoli L, et al. Extracellular Vesicle-packaged miRNA Release After Short-term Exposure to Particulate Matter Is Associated With Increased Coagulation. Part Fibre Toxicol. 2017 08 24;14(1):32. PubMed PMID: 28899404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular vesicle-packaged miRNA release after short-term exposure to particulate matter is associated with increased coagulation. AU - Pergoli,Laura, AU - Cantone,Laura, AU - Favero,Chiara, AU - Angelici,Laura, AU - Iodice,Simona, AU - Pinatel,Eva, AU - Hoxha,Mirjam, AU - Dioni,Laura, AU - Letizia,Marilena, AU - Albetti,Benedetta, AU - Tarantini,Letizia, AU - Rota,Federica, AU - Bertazzi,Pier Alberto, AU - Tirelli,Amedea Silvia, AU - Dolo,Vincenza, AU - Cattaneo,Andrea, AU - Vigna,Luisella, AU - Battaglia,Cristina, AU - Carugno,Michele, AU - Bonzini,Matteo, AU - Pesatori,Angela Cecilia, AU - Bollati,Valentina, Y1 - 2017/08/24/ PY - 2017/05/09/received PY - 2017/08/16/accepted PY - 2017/9/14/entrez PY - 2017/9/14/pubmed PY - 2018/5/22/medline KW - Air pollution KW - Cardiovascular disease KW - Extracellular vesicles KW - Fibrinogen KW - microRNAs SP - 32 EP - 32 JF - Particle and fibre toxicology JO - Part Fibre Toxicol VL - 14 IS - 1 N2 - 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. SN - 1743-8977 UR - https://www.unboundmedicine.com/medline/citation/28899404/Extracellular_vesicle_packaged_miRNA_release_after_short_term_exposure_to_particulate_matter_is_associated_with_increased_coagulation_ DB - PRIME DP - Unbound Medicine ER -