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Ultrafine Particulate Matter Exposure Impairs Vasorelaxant Response in Superoxide Dismutase 2-Deficient Murine Aortic Rings
Citation:
Carter, J., N. Madamanchi, G. Stouffer, M. Runge, W. Cascio, AND H. Tong. Ultrafine Particulate Matter Exposure Impairs Vasorelaxant Response in Superoxide Dismutase 2-Deficient Murine Aortic Rings. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, 81(5):106-115, (2018). https://doi.org/10.1080/15287394.2017.1420504
Impact/Purpose:
This research showed that the greater vascular effect in aortic rings in aged mice in vitro after ultrafine PM exposure is likely due to ultrafine PM-induced oxidative stress and loss of anti-oxidant defense in aged vascular tissue.
Description:
Background, studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism of adverse vascular effects. Advanced age is one factor known to decrease anti-oxidant defense and confer susceptibility to the detrimental vascular effects of PM exposure. The present study was designed to investigate the vasomotor responses after ultrafine PM exposure and the involved signaling pathways in wild type (WT) and superoxide dismutase 2 deficient (SOD2+/-) mice having decreased anti-oxidant defense. Methods, thoracic aortic rings isolated from young (4 mos. old) and aged (16 mos. old) WT and SOD2+/- mice were exposed to 50 µg/ml of Chapel Hill, NC ultrafine PM for 15 min in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with increasing concentrations of nitroglycerin (NTG). Results, we demonstrated that ultrafine PM decreased the relaxation response in both young WT (p<0.001) and young SOD2+/- (p<0.001) mouse aortas, and the relaxation was significantly decreased in young SOD2+/- mice compared to WT mice (p<0.01). Ultrafine PM significantly decreased the NTG-induced relaxation response in aged compared to young mouse aortas (p=0.012). After ultrafine PM exposure, the relaxation response did not differ between aged WT and aged SOD2+/- mice. In addition, we also showed that ultrafine PM enhanced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and ERK1/2 compared to the non-exposure control. While the phosphorylation of p38 MAPK and ERK1/2 was increased in the WT aged and SOD2+/- aorta versus WT young, the greatest increases were observed in the WT aged. Conclusion, this study indicates that the greater vascular effect in aortic rings in aged mice in vitro after ultrafine PM exposure is likely due to ultrafine PM-induced oxidative stress and loss of anti-oxidant defense in aged vascular tissue. Consistent with this conclusion is the attenuation of the NTG-induced relaxation response in young SOD2+/- mice.
URLs/Downloads:
DOI: Ultrafine Particulate Matter Exposure Impairs Vasorelaxant Response in Superoxide Dismutase 2-Deficient Murine Aortic Rings