Background: Epidemiologic 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. Results: We 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 Ca 2+ levels, reactive oxygen species (ROS) generation, and mRNA levels of the Ca 2+-regulating proteins, sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a), Ca 2+ /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. Threefold 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.
The plant Dendropanax morbifera Léveille (D. morbifera), a subtropical broad-leaved evergreen tree, have been used in folk medicine for the treatment of infectious diseases, skin diseases, and other maladies. However, the effect of extracts from D. morbifera in vascuar diseases has not yet been reported. In this study, BrdU assay revealed that extracts from D. morbifera inhibit significantly the proliferation rate of Rat Aortic Smooth Muscle Cells (RAoSMCs) by -40% in treated samples compared to controls. Notably, 2-D wound healing assay and 3-D boyden chamber assay showed the significant reduction of RAoSMCs migration induced by serum in nano extracts treated groups by -50%. We further observed that the phosphorylated levels of Akt and ERK were significantly reduced by 70% in extracts treated RAoSMCs. Moreover, the expression levels of matrix metalloproteinase (MMP) 2 and 9 were significantly reduced by extracts from D. morbifera. Our results suggest that extracts from D. morbifera inhibit proliferation and migration in RAoSMCs via the modulation of phosphorylated levels of Akt and ERK. Subsequently, the reduced MMP2 and 9 expression might result to reduced migration of RAoSMCs.
Phytoncide, nanochemicals extracted from Chamaecyparis obtusa (C. obtusa), is reported to possess many pharmacological activities including immunological stimulating, anti-cancer, antioxidant, and antiinflammatory activities. However, the effect of phytoncide in vascuar diseases, especially on the behavior of vascular smooth muscle cells, has not yet been clearly elucidated. Therefore, in the present study, we investigated the effects of 15 kinds of phytoncide by various extraction conditions from C. obtusa on the proliferation and migration in rat aortic smooth muscle cells (RAoSMCs). First of all, we determined the concentration of each extracts not having cytotoxicity by MTT assay. We observed that the proliferation rate measured using BrdU assay was significantly reduced by supercritical fluid, steam distillation, Me-OH, and hexane extraction fraction in order with higher extent, respectively. Moreover, the treatment of above nanofractions inhibit the migration of RAoSMCs by 40%, 60%, and 30%, respectively, both in 2-D wound healing assay and 3-D boyden chamber assay. Immunoblot revealed that the phosphorylated levels of Akt and ERK were significantly reduced in nanofractions treated RAoSMCs. Taken together, these data suggest that phytoncide extracted from C. obtusa inhibits proliferation and migration in RAoSMCs via the modulation of phosphorylated levels of Akt and ERK. Therefore, phytoncide nanomolecules might be a potential therapeutic approach to prevent or treat atheroscrelosis and restenosis.
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