Research from JAMA — Long-term Air Pollution Exposure and Acceleration of Atherosclerosis and Vascular Inflammation in an Animal Model — ContextRecent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined.ObjectiveTo test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model.Design, Setting, and ParticipantsBetween July 21, 2004, and January 12, 2005, 28 apolipoprotein E−/− (apoE−/−) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 μm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months.Main Outcome MeasuresComposite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes.ResultsIn the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] × 10-8 vs 4.3 [0.1] × 10-8, respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001).ConclusionIn an apoE−/− mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.

Background— There is a strong link between urbanization and type 2 diabetes mellitus. Although a multitude of mechanisms have been proposed, there are no studies evaluating the impact of ambient air pollutants and the propensity to develop type 2 diabetes mellitus. We hypothesized that exposure to ambient fine particulate matter (<2.5 μm; PM _2.5 ) exaggerates diet-induced insulin resistance, adipose inflammation, and visceral adiposity. Methods and Results— Male C57BL/6 mice were fed high-fat chow for 10 weeks and randomly assigned to concentrated ambient PM _2.5 or filtered air (n=14 per group) for 24 weeks. PM _2.5 -exposed C57BL/6 mice exhibited marked whole-body insulin resistance, systemic inflammation, and an increase in visceral adiposity. PM _2.5 exposure induced signaling abnormalities characteristic of insulin resistance, including decreased Akt and endothelial nitric oxide synthase phosphorylation in the endothelium and increased protein kinase C expression. These abnormalilties were associated with abnormalities in vascular relaxation to insulin and acetylcholine. PM _2.5 increased adipose tissue macrophages (F4/80 ⁺ cells) in visceral fat expressing higher levels of tumor necrosis factor-α/interleukin-6 and lower interleukin-10/ N -acetyl-galactosamine specific lectin 1. To test the impact of PM _2.5 in eliciting direct monocyte infiltration into fat, we rendered FVBN mice expressing yellow fluorescent protein (YFP) under control of a monocyte-specific promoter (c- fms , c- fms ^YFP ) diabetic over 10 weeks and then exposed these mice to PM _2.5 or saline intratracheally. PM _2.5 induced YFP cell accumulation in visceral fat and potentiated YFP cell adhesion in the microcirculation. Conclusion— PM _2.5 exposure exaggerates insulin resistance and visceral inflammation/adiposity. These findings provide a new link between air pollution and type 2 diabetes mellitus.

Particulate air pollution has been associated with respiratory and cardiovascular disease. Evidence for cardiovascular and neurodegenerative effects of ambient particles was reviewed as part of a workshop. The purpose of this critical update is to summarize the evidence presented for the mechanisms involved in the translocation of particles from the lung to other organs and to highlight the potential of particles to cause neurodegenerative effects.

Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences. Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences.

We review literature providing insights on health-related effects caused by inhalation of ambient air particulate matter (PM) containing metals, emphasizing effects associated with in vivo exposures at or near contemporary atmospheric concentrations. Inhalation of much higher concentrations, and high-level exposures via intratracheal (IT) instillation that inform mechanistic processes, are also reviewed. The most informative studies of effects at realistic exposure levels, in terms of identifying influential individual PM components or source-related mixtures, have been based on (1) human and laboratory animal exposures to concentrated ambient particles (CAPs), and (2) human population studies for which both health-related effects were observed and PM composition data were available for multipollutant regression analyses or source apportionment. Such studies have implicated residual oil fly ash (ROFA) as the most toxic source-related mixture, and Ni and V, which are characteristic tracers of ROFA, as particularly influential components in terms of acute cardiac function changes and excess short-term mortality. There is evidence that other metals within ambient air PM, such as Pb and Zn, also affect human health. Most evidence now available is based on the use of ambient air PM components concentration data, rather than actual exposures, to determine significant associations and/or effects coefficients. Therefore, considerable uncertainties about causality are associated with exposure misclassification and measurement errors. As more PM speciation data and more refined modeling techniques become available, and as more CAPs studies involving PM component analyses are performed, the roles of specific metals and other components within PM will become clearer.

The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ...