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Short-term particulate matter exposure induces extracellular vesicle release in overweight subjects.

ABSTRACT: Extracellular vesicles (EVs) represent a plausible molecular mechanism linking particulate matter (PM) inhalation to its systemic effects. Microvesicles (MVs) are released from many cell types in response to various stimuli. Increased body mass index (BMI) could modify the response to PM exposure due to enhanced PM uptake and/or an underlying pro-oxidative state. We investigated the relationship between EV release and PM10/PM2.5 exposure in a cohort of 51 volunteers. Subjects were stratified based on their BMI to evaluate whether overweight BMI is a determinant of hypersusceptibility to PM effects.Exposure to PM10/PM2.5 was assessed with a personal sampler worn for 24hours before plasma collection and confirmed with monitoring station data. Size and cellular origin of plasma EVs were characterized by Nanosight analysis and flow cytometry, respectively. Multivariate regression models were run after log-transformation, stratifying subjects based on BMI (? or <25kg/m2). PM exposure resulted in increased release of EVs, with the maximum observed effect for endothelial MVs. For PM10 and PM2.5, the adjusted geometric mean ratio and 95% confidence interval were 3.47 (1.30, 9.27) and 3.14 (1.23, 8.02), respectively. Compared to those in normal subjects, PM-induced EV alterations in overweight subjects were more pronounced, with visibly effect in all MV subtypes, particularly endothelial MVs.Our findings emphasize the role of EV release after PM exposure and the susceptibility of overweight subjects. Larger studies with accurate exposure assessment and complete EVs characterization/content analysis, could further clarify the molecular mechanism responsible for PM effects and of hypersusceptibility of overweight subjects.

SUBMITTER: Bonzini M

PROVIDER: S-EPMC5380126 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Short-term particulate matter exposure induces extracellular vesicle release in overweight subjects.

Bonzini Matteo M Pergoli Laura L Cantone Laura L Hoxha Mirjam M Spinazzè Andrea A Del Buono Luca L Favero Chiara C Carugno Michele M Angelici Laura L Broggi Lucia L Cattaneo Andrea A Pesatori Angela C AC Bollati Valentina V

Environmental research 20170310

<h4>Background</h4>Extracellular vesicles (EVs) represent a plausible molecular mechanism linking particulate matter (PM) inhalation to its systemic effects. Microvesicles (MVs) are released from many cell types in response to various stimuli. Increased body mass index (BMI) could modify the response to PM exposure due to enhanced PM uptake and/or an underlying pro-oxidative state. We investigated the relationship between EV release and PM<sub>10</sub>/PM<sub>2.5</sub> exposure in a cohort of 51 ...[more]

PMID: 28231550

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Project description:BackgroundExposure 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.ResultsShort-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.ConclusionsResearch 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.

Dataset Information

Short-term particulate matter exposure induces extracellular vesicle release in overweight subjects.

Publications

Short-term particulate matter exposure induces extracellular vesicle release in overweight subjects.

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