Oxygenated polycyclic aromatic hydrocarbons from ambient particulate matter induce electrophysiological instability in cardiomyocytes

Sujin Ju,Han-Yi Jiao,Ji Yi Lee,Leejin Lim,Heesang Song,Young-Jae Ki,Seok Choi,Dong-Hyun Choi,Jae Yeoul Jun

doi:10.1186/s12989-020-00351-5

Sujin Ju, Han-Yi Jiao + Show 7 more

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https://doi.org/10.1186/s12989-020-00351-5

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Abstract

BackgroundEpidemiologic studies have suggested that elevated concentrations of particulate matter (PM) are strongly associated with an increased risk of developing cardiovascular diseases, including arrhythmia. However, the cellular and molecular mechanisms by which PM exposure causes arrhythmia and the component that is mainly responsible for this adverse effect remains to be established. In this study, the arrhythmogenicity of mobilized organic matter from two different types of PM collected during summer (SPM) and winter (WPM) seasons in the Seoul metropolitan area was evaluated. In addition, differential effects between polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs (oxy-PAHs) on the induction of electrophysiological instability were examined.ResultsWe extracted the bioavailable organic contents of ambient PM, measuring 10 μm or less in diameter, collected from the Seoul metropolitan area using a high-volume air sampler. Significant alterations in all factors tested for association with electrophysiological instability, such as intracellular Ca2+ levels, reactive oxygen species (ROS) generation, and mRNA levels of the Ca2+-regulating proteins, sarcoplasmic reticulum Ca2+ATPase (SERCA2a), Ca2+/calmodulin-dependent protein kinase II (CaMK II), and ryanodine receptor 2 (RyR2) were observed in cardiomyocytes treated with PM. Moreover, the alterations were higher in WPM-treated cardiomyocytes than in SPM-treated cardiomyocytes. Three-fold more oxy-PAH concentrations were observed in WPM than SPM. As expected, electrophysiological instability was induced higher in oxy-PAHs (9,10-anthraquinone, AQ or 7,12-benz(a) anthraquinone, BAQ)-treated cardiomyocytes than in PAHs (anthracene, ANT or benz(a) anthracene, BaA)-treated cardiomyocytes; oxy-PAHs infusion of cells mediated by aryl hydrocarbon receptor (AhR) was faster than PAHs infusion. In addition, ROS formation and expression of calcium-related genes were markedly more altered in cells treated with oxy-PAHs compared to those treated with PAHs.ConclusionsThe concentrations of oxy-PAHs in PM were found to be higher in winter than in summer, which might lead to greater electrophysiological instability through the ROS generation and disruption of calcium regulation.

Highlights

Epidemiologic studies have suggested that elevated concentrations of particulate matter (PM) are strongly associated with an increased risk of developing cardiovascular diseases, including arrhythmia
The concentrations of oxy-polycyclic aromatic hydrocarbons (PAHs) in PM were found to be higher in winter than in summer, which might lead to greater electrophysiological instability through the reactive oxygen species (ROS) generation and disruption of calcium regulation
We observed that action potential duration (APD) increased immediately after switching to PM-containing solution; it increased with time and reached a steady state within 5 min

Summary

Introduction

Epidemiologic studies have suggested that elevated concentrations of particulate matter (PM) are strongly associated with an increased risk of developing cardiovascular diseases, including arrhythmia. Exposure to ambient particulate matter (PM) is associated with increased cardiovascular morbidity and mortality. After revealing the association between PM exposure and the causative risks involved in all mortality cases in the US [1], various epidemiological and experimental studies have reported that elevated PM concentrations were closely associated with increase in cardiovascular diseases (CVD), including myocardial infarction, stroke, arrhythmia, and venous thromboembolism [2,3,4]. Experimental studies have suggested that PM exposure increases cardiac oxidative stress and electrophysiological changes in rats [10, 11]. Kim et al demonstrated that arrhythmic parameters, such as action potential duration (APD), early afterdepolarization (EAD), and ventricular tachycardia (VT), were significantly increased in diesel exhausted particle (DEP)-infused rat hearts due to oxidative stress and calcium kinase II activation [9]

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