Dataset Information

Ambient particulate matter and microRNAs in extracellular vesicles: a pilot study of older individuals.

ABSTRACT:

Background

Air pollution from particulate matter (PM) has been linked to cardiovascular morbidity and mortality; however the underlying biological mechanisms remain to be uncovered. Gene regulation by microRNAs (miRNAs) that are transferred between cells by extracellular vesicles (EVs) may play an important role in PM-induced cardiovascular risk. This study sought to determine if ambient PM2.5 levels are associated with expression of EV-encapsulated miRNAs (evmiRNAs), and to investigate the participation of such evmiRNAs in pathways related to cardiovascular disease (CVD).

Methods

We estimated the short- (1-day), intermediate- (1-week and 1-month) and long-term (3-month, 6-month, and 1-year) moving averages of ambient PM2.5 levels at participants' addresses using a validated hybrid spatio-temporal land-use regression model. We collected 42 serum samples from 22 randomly selected participants in the Normative Aging Study cohort and screened for 800 miRNAs using the NanoString nCounter® platform. Mixed effects regression models, adjusted for potential confounders were used to assess the association between ambient PM2.5 levels and evmiRNAs. All p-values were adjusted for multiple comparisons. In-silico Ingenuity Pathway Analysis (IPA) was performed to identify biological pathways that are regulated by PM-associated evmiRNAs.

Results

We found a significant association between long-term ambient PM2.5 exposures and levels of multiple evmiRNAs circulating in serum. In the 6-month window, ambient PM2.5 exposures were associated with increased levels of miR-126-3p (0.74?±?0.21; p?=?0.02), miR-19b-3p (0.52?±?0.15; p?=?0.02), miR-93-5p (0.78?±?0.22; p?=?0.02), miR-223-3p (0.74?±?0.22; p?=?0.02), and miR-142-3p (0.81?±?0.21; p?=?0.03). Similarly, in the 1-year window, ambient PM2.5 levels were associated with increased levels of miR-23a-3p (0.83?±?0.23; p?=?0.02), miR-150-5p (0.90?±?0.24; p?=?0.02), miR-15a-5p (0.70?±?0.21; p?=?0.02), miR-191-5p (1.20?±?0.35; p?=?0.02), and let-7a-5p (1.42?±?0.39; p?=?0.02). In silico pathway analysis on PM2.5-associated evmiRNAs identified several key CVD-related pathways including oxidative stress, inflammation, and atherosclerosis.

Conclusions

We found an association between long-term ambient PM2.5 levels and increased levels of evmiRNAs circulating in serum. Further observational studies are warranted to confirm and extend these important findings in larger and more diverse populations, and experimental studies are needed to elucidate the exact roles of evmiRNAs in PM-induced CVD.

SUBMITTER: Rodosthenous RS

PROVIDER: S-EPMC4782360 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Publications

Ambient particulate matter and microRNAs in extracellular vesicles: a pilot study of older individuals.

Rodosthenous Rodosthenis S RS Coull Brent A BA Lu Quan Q Vokonas Pantel S PS Schwartz Joel D JD Baccarelli Andrea A AA

Particle and fibre toxicology 20160308

<h4>Background</h4>Air pollution from particulate matter (PM) has been linked to cardiovascular morbidity and mortality; however the underlying biological mechanisms remain to be uncovered. Gene regulation by microRNAs (miRNAs) that are transferred between cells by extracellular vesicles (EVs) may play an important role in PM-induced cardiovascular risk. This study sought to determine if ambient PM2.5 levels are associated with expression of EV-encapsulated miRNAs (evmiRNAs), and to investigate ...[more]

PMID: 26956024

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Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Keywords: gene expression

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Dataset Information

Ambient particulate matter and microRNAs in extracellular vesicles: a pilot study of older individuals.

Background

Methods

Results

Conclusions

Publications

Ambient particulate matter and microRNAs in extracellular vesicles: a pilot study of older individuals.

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