DNA Hypomethylation, Ambient Particulate Matter, and Increased Blood Pressure: Findings From Controlled Human Exposure Experiments

Background: Short‐term exposures to fine (<2.5 μm aerodynamic diameter) ambient particulate‐matter (PM) have been related with increased blood pressure (BP) in controlled‐human exposure and community‐based studies. However, whether coarse (2.5 to 10 μm) PM exposure increases BP is uncertain. Recent observational studies have linked PM exposures with blood DNA hypomethylation, an epigenetic alteration that activates inflammatory and vascular responses. No experimental evidence is available to confirm those observational data and demonstrate the relations between PM, hypomethylation, and BP. Methods and Results: We conducted a cross‐over trial of controlled‐human exposure to concentrated ambient particles (CAPs). Fifteen healthy adult participants were exposed for 130 minutes to fine CAPs, coarse CAPs, or HEPA‐filtered medical air (control) in randomized order with ≥2‐week washout. Repetitive‐element (Alu, long interspersed nuclear element‐1 [LINE‐1]) and candidate‐gene (TLR4, IL‐12, IL‐6, iNOS) blood methylation, systolic and diastolic BP were measured pre‐ and postexposure. After adjustment for multiple comparisons, fine CAPs exposure lowered Alu methylation (β‐standardized=−0.74, adjusted‐P=0.03); coarse CAPs exposure lowered TLR4 methylation (β‐standardized=−0.27, adjusted‐P=0.04). Both fine and coarse CAPs determined significantly increased systolic BP (β=2.53 mm Hg, P=0.001; β=1.56 mm Hg, P=0.03, respectively) and nonsignificantly increased diastolic BP (β=0.98 mm Hg, P=0.12; β=0.82 mm Hg, P=0.11, respectively). Decreased Alu and TLR4 methylation was associated with higher postexposure DBP (β‐standardized=0.41, P=0.04; and β‐standardized=0.84, P=0.02; respectively). Decreased TLR4 methylation was associated with higher postexposure SBP (β‐standardized=1.45, P=0.01). Conclusions: Our findings provide novel evidence of effects of coarse PM on BP and confirm effects of fine PM. Our results provide the first experimental evidence of PM‐induced DNA hypomethylation and its correlation to BP.Version of Recor

Controlled Exposure Study of Air Pollution and T-Wave Alternans in Volunteers without Cardiovascular Disease

Background: Epidemiological studies have assessed T-wave alternans (TWA) as a possible mechanism of cardiac arrhythmias related to air pollution in high-risk subjects and have reported associations with increased TWA magnitude. Objective: In this controlled human exposure study, we assessed the impact of exposure to concentrated ambient particulate matter (CAP) and ozone (O:3) on T-wave alternans in resting volunteers without preexisting cardiovascular disease. Methods: Seventeen participants without preexisting cardiovascular disease were randomized to filtered air (FA), CAP (150 μg/m3), O3 (120 ppb), or combined CAP + O3 exposures for 2 hr. Continuous electrocardiograms (ECGs) were recorded at rest and T-wave alternans (TWA) was computed by modified moving average analysis with QRS alignment for the artifact-free intervals of 20 beats along the V2 and V5 leads. Exposure-induced changes in the highest TWA magnitude (TWAMax) were estimated for the first and last 5 min of each exposure (TWAMax_Early and TWAMax_Late respectively). ΔTWAMax (Late–Early) were compared among exposure groups using analysis of variance. Results: Mean ± SD values for ΔTWA:Max were –2.1 ± 0.4, –2.7 ± 1.1, –1.9 ± 1.5, and –1.2 ± 1.5 in FA, CAP, O3, and CAP + O3 exposure groups, respectively. No significant differences were observed between pollutant exposures and FA. Conclusion: In our study of 17 volunteers who had no preexisting cardiovascular disease, we did not observe significant changes in T-wave alternans after 2-hr exposures to CAP, O:3, or combined CAP + O3. This finding, however, does not preclude the possibility of pollution-related effects on TWA at elevated heart rates, such as during exercise, or the possibility of delayed responses

Air pollution and the microvasculature: A cross-sectional assessment of in vivo retinal images in the population-based multi-ethnic study of atherosclerosis (MESA)

10.1371/journal.pmed.1000372PLoS Medicine711

Acute Blood Pressure Responses in Healthy Adults During Controlled Air Pollution Exposures

Exposure to air pollution has been shown to cause arterial vasoconstriction and alter autonomic balance. Because these biologic responses may influence systemic hemodynamics, we investigated the effect of air pollution on blood pressure (BP). Responses during 2-hr exposures to concentrated ambient fine particles (particulate matter < 2.5 μm in aerodynamic diameter; PM(2.5)) plus ozone (CAP+O(3)) were compared with those of particle-free air (PFA) in 23 normotensive, non-smoking healthy adults. Mean concentrations of PM(2.5) were 147 ± 27 versus 2 ± 2 μg/m(3), respectively, and those of O(3) were 121 ± 3 versus 8 ± 5 ppb, respectively (p < 0.0001 for both). A significant increase in diastolic BP (DBP) was observed at 2 hr of CAP+O(3) [median change, 6 mm Hg (9.3%); binomial 95% confidence interval (CI), 0 to 11; p = 0.013, Wilcoxon signed rank test] above the 0-hr value. This increase was significantly different (p = 0.017, unadjusted for basal BP) from the small 2-hr change during PFA (median change, 1 mm Hg; 95% CI, −2 to 4; p = 0.24). This prompted further investigation of the CAP+O(3) response, which showed a strong association between the 2-hr change in DBP (and mean arterial pressure) and the concentration of the organic carbon fraction of PM(2.5) (r = 0.53, p < 0.01; r = 0.56, p < 0.01, respectively) but not with total PM(2.5) mass (r ≤ 0.25, p ≥ 0.27). These findings suggest that exposure to environmentally relevant concentrations of PM(2.5) and O(3) rapidly increases DBP. The magnitude of BP change is associated with the PM(2.5) carbon content. Exposure to vehicular traffic may provide a common link between our observations and previous studies in which traffic exposure was identified as a potential risk factor for cardiovascular disease

Global Education Handbook: Modules for Teaching Pre-School to Secondary School

This handbook was developed to assist K-12 teachers who wish to introduce a global perspective into their curriculum. The modules were developed by classroom teachers and include such topics as: Anti-bias Curriculum: A Multicultural Perspective,” “The African Influence in Puerto Rican Music,” and “Multicultural Education: An Approach through Beauty, Fashion and Art.” Organized according to grade levels, each module is divided into a series of lessons complete with objectives and a detailed description of materials and activities. It is the purpose of the Global Education Handbook to contribute to networking within the community of educators, locally and globally. The Handbook provides examples of lesson plans and units with a global perspective for use at the pre-school, elementary, middle, and secondary grade levels. It identifies a global network of resources which is available to educators who want to bring the world into their classrooms. Included is an account of an early childhood educator in a rural elementary school in Western Massachusetts who is attempting to instill a global perspective in her curriculum. Her experiences bring to light many of the challenges which confront new and veteran educators who wish to globalize their classrooms and their schools. The Handbook is organized into chapters according to grade level: pre-school, elementary, middle, and secondary. The material within each of these chapters was developed by teachers who implemented these global education units in their classrooms. Each unit is comprised of several lessons that have either a geographic, cultural, or issue-based focus. These resources can be used directly from the Handbook and it is hoped that they will inspire the development of other lessons and units particular to the unique needs of each educator

Diffusion and drift of cosmic rays in highly turbulent magnetic fields

We determine numerically the parallel, perpendicular, and antisymmetric diffusion coefficients for charged particles propagating in highly turbulent magnetic fields, by means of extensive Monte Carlo simulations. We propose simple expressions, given in terms of a small set of fitting parameters, to account for the diffusion coefficients as functions of magnetic rigidity and turbulence level, and corresponding to different kinds of turbulence spectra. The results obtained satisfy scaling relations, which make them useful for describing the cosmic ray origin and transport in a variety of different astrophysical environments.Comment: 17 pages, 7 figure

Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation

Aim: Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution. Methods and results: To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 +/- 4 vs. 133 +/- 3 mmHg, P &lt; 0.05) and attenuated vasodilatation to bradykinin (P = 0.005), acetylcholine (P = 0.008), and sodium nitroprusside (P &lt; 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n = 6-9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P &lt; 0.001) and sodium-nitroprusside (P = 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate. Conclusion: Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions.</p

Cardiovascular health and particulate vehicular emissions: a critical evaluation of the evidence

A major public health goal is to determine linkages between specific pollution sources and adverse health outcomes. This paper provides an integrative evaluation of the database examining effects of vehicular emissions, such as black carbon (BC), carbonaceous gasses, and ultrafine PM, on cardiovascular (CV) morbidity and mortality. Less than a decade ago, few epidemiological studies had examined effects of traffic emissions specifically on these health endpoints. In 2002, the first of many studies emerged finding significantly higher risks of CV morbidity and mortality for people living in close proximity to major roadways, vs. those living further away. Abundant epidemiological studies now link exposure to vehicular emissions, characterized in many different ways, with CV health endpoints such as cardiopulmonary and ischemic heart disease and circulatory-disease-associated mortality; incidence of coronary artery disease; acute myocardial infarction; survival after heart failure; emergency CV hospital admissions; and markers of atherosclerosis. We identify numerous in vitro, in vivo, and human panel studies elucidating mechanisms which could explain many of these cardiovascular morbidity and mortality associations. These include: oxidative stress, inflammation, lipoperoxidation and atherosclerosis, change in heart rate variability (HRV), arrhythmias, ST-segment depression, and changes in vascular function (such as brachial arterial caliber and blood pressure). Panel studies with accurate exposure information, examining effects of ambient components of vehicular emissions on susceptible human subjects, appear to confirm these mechanisms. Together, this body of evidence supports biological mechanisms which can explain the various CV epidemiological findings. Based upon these studies, the research base suggests that vehicular emissions are a major environmental cause of cardiovascular mortality and morbidity in the United States. As a means to reduce the public health consequences of such emissions, it may be desirable to promulgate a black carbon (BC) PM2.5 standard under the National Ambient Air Quality Standards, which would apply to both on and off-road diesels. Two specific critical research needs are identified. One is to continue research on health effects of vehicular emissions, gaseous as well as particulate. The second is to utilize identical or nearly identical research designs in studies using accurate exposure metrics to determine whether other major PM pollutant sources and types may also underlie the specific health effects found in this evaluation for vehicular emissions