Ambient Particulates Alter Vascular Function through Induction of Reactive Oxygen and Nitrogen Species
- 30 January 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 111 (1), 80-88
- https://doi.org/10.1093/toxsci/kfp004
Abstract
Previous studies have shown a link between inhaled particulate matter (PM) exposure in urban areas and susceptibility to cardiovascular diseases. Although an oxidative stress pathway is strongly implicated, the locus of generation of reactive oxygen species (ROS) and the mechanisms by which these radicals exert their effects remain to be characterized. To test the hypothesis that exposure to environmentally relevant inhaled concentrated ambient PM (CAPs) enhances atherosclerosis through induction of vascular ROS and reactive nitrogen species. High-fat chow fed apolipoprotein E–/– mice were exposed to CAPs of less than 2.5 μm (PM2.5) or filtered air (FA), for 6 h/day, 5 days/week, for 4 months in Manhattan, NY. Atherosclerotic lesions were analyzed by histomorphometricly. Vascular reactivity, superoxide generation, mRNA expression of NADPH (nicotinamide adenine dinucleotide phosphate, reduced) oxidase subunits, inducible nitric oxide synthase, endothelial nitric oxide synthase, and GTP cyclohydrolase I were also assessed. Manhattan PM2.5 CAPs were characterized by higher concentrations of organic and elemental carbon. Analysis of vascular responses revealed significantly decreased phenylephrine constriction in CAPs-exposed mice, which was restored by a soluble guanine cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. Vascular relaxation to A23187, but not to acetylcholine, was attenuated in CAPs mice. Aortic expression of NADPH oxidase subunits (p47phox and rac1) and iNOS were markedly increased, paralleled by increases in superoxide generation and extensive protein nitration in the aorta. The composite plaque area of thoracic aorta was significantly increased with pronounced macrophage infiltration and lipid deposition in the CAPs mice. CAPs exposure in Manhattan alters vasomotor tone and enhances atherosclerosis through NADPH oxidase dependent pathways.Keywords
This publication has 40 references indexed in Scilit:
- Air Pollution Exposure Potentiates Hypertension Through Reactive Oxygen Species-Mediated Activation of Rho/ROCKArteriosclerosis, Thrombosis, and Vascular Biology, 2008
- Particulate matter exposure induces persistent lung inflammation and endothelial dysfunctionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2008
- CARDIOVASCULAR EFFECTS OF PEROXYNITRITEClinical and Experimental Pharmacology and Physiology, 2007
- Air Pollution and AtherothrombosisInhalation Toxicology, 2007
- Importance of Size and Composition of Particles for Effects on Cells In VitroInhalation Toxicology, 2007
- Identifying and quantifying transported vs. local sources of New York City PM2.5 fine particulate matter air pollutionAtmospheric Environment, 2006
- The Effect of Particulate Matter on Resistance and Conductance Vessels in the RatInhalation Toxicology, 2004
- Motorcycle Exhaust Particulates Enhance Vasoconstriction in Organ Culture of Rat Aortas and Involve Reactive Oxygen SpeciesToxicological Sciences, 2003
- Air Pollution and Cause-Specific Mortality in Milan, Italy, 1980–1989Archives of environmental health, 1999
- SOLUBLE TRANSITION METALS MEDIATE RESIDUAL OIL FLY ASH INDUCED ACUTE LUNG INJURYJournal of Toxicology and Environmental Health, 1997