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Soluble Components of Ultraflne Particulate Matter Stimulate Endothelial H202 Production
Citation:
Snow, S. AND M. S. CARRAWAY. Soluble Components of Ultraflne Particulate Matter Stimulate Endothelial H202 Production. Presented at Society of Toxicology Annual Meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
SaSalt Lake This manuscript focuses on mitochondrial biogenesis, a fundamental adaptive response of the cardiovascular system following exposure to a variety of diseases and environmental stressors
Description:
A growing body of evidence shows a strong association between particulate matter (PM) exposure and adverse cardiovascular health effects such as atherosclerosis and myocardial ischemia. The mechanisms by which PM causes cardiovascular dysfunction is unknown, but there is increasing evidence for a role of ultrafine (UF) particles with a diameter of <0.1 urn in cardiovascular effects of air pollution. While it is unlikely that PM can enter the circulation from the alveolar compartment, the soluble components of UF particles could directly cause oxidative stress, pro-inflammatory, and pro-coagulant changes in endothelial and cardiac cells. We hypothesize that the soluble components of ultrafine air pollution particles induce ROS formation in endothelial cells by activation of specific enzymatic sources. We quantified cellular H20 2 production using the Amplex . Red assay in an endothelial cell line immediately following exposure to either UF particles, or their insoluble and soluble fractions at 10, 50, and 100 jlg/ml. To identify cellular sources of ROS, we measured H20 2 production after cells were pretreated with chemical inhibitors of key endothelial ROS generating systems. We determined that the soluble components of UF particles are primarily responsible for increased H20 2 production. We also found that PM-induced H20 2 production was dose-dependent, and was inhibited by the NADPH Oxidase (NOX) inhibitor diphenyliodonium (DPI). Mitochondrial and xanthine oxidase inhibitors (allopurinol, potassium cyanide, and rotenone) did not diminish particle-induced H202 production. Protein and mRNA analysis showed that NOX-4 was the primary NOX homologue present in this endothelial cell line. These data strongly suggests that NOX-4 is rapidly activated by the soluble components of UF particles to produce H202 in endothelial cells. This work has important implications for mechanisms of vascular effects of inhaled PM. Disclosures. No author has any conflict of interest to disclose. The research described in this article has been reviewed by the HealthEffects and Environmental Research Laboratory, United States Environmental Protection Agency, and has been approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.