Ambient Fine Particulate Matter Induces Apoptosis of Endothelial Progenitor Cells Through Reactive Oxygen Species Formation

Abstract

Background/Aims: Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in angiogenesis and vascular repair. Some environmental insults, like fine particulate matter (PM) exposure, significantly impair cardiovascular functions. However, the mechanisms for PM-induced adverse effects on cardiovascular system remain largely unknown. The present research was to study the detrimental effects of PM on EPCs and explore the potential mechanisms. Methods: PM was intranasal-distilled into male C57BL/6 mice for one month. Flow cytometry was used to measure the number of EPCs, apoptosis level of circulating EPCs and intracellular reactive oxygen species (ROS) formation. Serum TNF- α and IL-1β were measured using ELISA. To determine the role of PM-induced ROS in EPC apoptosis, PM was co-administrated with the antioxidant N-acetylcysteine (NAC) in wild type mice or used in a triple transgenic mouse line (TG) with overexpression of antioxidant enzyme network (AON) composed of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase (Gpx-1) with decreased in vivo ROS production. Results: PM treatment significantly decreased circulating EPC population, promoted apoptosis of EPCs in association with increased ROS production and serum TNF-α and IL-1β levels, which could be effectively reversed by either NAC treatment or overexpression of AON. Conclusion: PM exposure significantly decreased circulating EPCs population due to increased apoptosis via ROS formation in mice.

Evaluation of the Effects of Airborne Particulate Matter on Bone Marrow-Mesenchymal Stem Cells (BM-MSCs): Cellular, Molecular and Systems Biological Approaches

“…This was in tandem with our current gene expression analysis, which showed increased expression of inflammatory cytokines namely TNF-α and IL-6 following exposure to both PM2.5 and PM10. These results are in agreement with a previously reported studies in which PM2.5-10 increased the expression levels of the inflammatory markers including TNF-α and IL-1β in endothelial progenitor cells [37], IL-6 and IL-8 in monocytes [38], IL-6 in Kupffer cells [39] and TNF-α, IL-6 and IL-8 in lung epithelial cells [40]. The mechanism through which the airborne particulates induced apoptosis and increased the expression level of the inflammatory markers was attributed to triggering the formation of the reactive oxygen species (ROS) [37,40,41].…”

Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo

“…* placebo treatment vs healthy control, P<0.05, n=5; ** probucol treatment vs healthy control, p<0.05, n=5; # probucol treatment vs placebo, p<0.05, n=5. stress were involved in EPC dysfunction in many diseases including hyperlipidemia, diabetes, coronary artery disease, renal ischemia-reperfusion injury and air pollution related cardiovascular disease [64][65][66][67]. Our data showed that ox-LDL was able to increase both BM and blood extracellular and blood intracellular ROS levels in mouse with ox-LDL treatment.…”

TNF-α Activates High-Mobility Group Box 1 - Toll-Like Receptor 4 Signaling Pathway in Human Aortic Endothelial Cells

“…It is consistent with our previous study of renal tubular epithelial cells [11] in which high glucose stimulation caused an immediate increase in the association of HMGB1 with TLR4, and this effect of high glucose was dependent on ROS production. ROS are generated by a variety of stimuli and act as a signaling molecule [30,31], and our data suggest that HMGB1-TLR4 axis could be a common downstream signal of ROS.…”