Ultrafine Particle Exposure Reveals the Importance of FOXO1/Notch Activation Complex for Vascular Regeneration.
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ABSTRACT: Aims
Redox active ultrafine particles (UFP, d?ResultsIn a zebrafish model of tail injury and repair, transgenic Tg(fli1:GFP) embryos developed vascular regeneration at 3 days post amputation (dpa), whereas UFP exposure impaired regeneration (p?
SUBMITTER: Baek KI
PROVIDER: S-EPMC5912723 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
Ultrafine Particle Exposure Reveals the Importance of FOXO1/Notch Activation Complex for Vascular Regeneration.
Baek Kyung In KI Packard René R Sevag RRS Hsu Jeffrey J JJ Saffari Arian A Ma Zhao Z Luu Anh Phuong AP Pietersen Andrew A Yen Hilary H Ren Bin B Ding Yichen Y Sioutas Constantinos C Li Rongsong R Hsiai Tzung K TK
Antioxidants & redox signaling 20171117 13
<h4>Aims</h4>Redox active ultrafine particles (UFP, d < 0.2 μm) promote vascular oxidative stress and atherosclerosis. Notch signaling is intimately involved in vascular homeostasis, in which forkhead box O1 (FOXO1) acts as a co-activator of the Notch activation complex. We elucidated the importance of FOXO1/Notch transcriptional activation complex to restore vascular regeneration after UFP exposure.<h4>Results</h4>In a zebrafish model of tail injury and repair, transgenic Tg(fli1:GFP) embryos d ...[more]
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Project description:High ambient ultrafine particle (UFP) concentrations may play an important role in the adverse health effects associated with living near busy roadways. However, UFP size distributions change rapidly as vehicle emissions dilute and age. These size changes can influence UFP lung deposition rates and dose because deposition in the respiratory system is a strong function of particle size. Few studies to date have measured and characterized changes in near-road UFP size distributions in real-time, thus missing transient variations in size distribution due to short-term fluctuations in wind speed, direction, or particle dynamics. In this study we measured important wind direction effects on near-freeway UFP size distributions and gradients using a mobile platform with 5-s time resolution. Compared to more commonly measured perpendicular (downwind) conditions, parallel wind conditions appeared to promote formation of broader and larger size distributions of roughly one-half the particle concentration. Particles during more parallel wind conditions also changed less in size with downwind distance and the fraction of lung-deposited particle number was calculated to be 15% lower than for downwind conditions, giving a combined decrease of about 60%. In addition, a multivariate analysis of several variables found meteorology, particularly wind direction and temperature, to be important in predicting UFP concentrations within 150 m of a freeway (R2 = 0.46, p = 0.014).
| S-EPMC3886859 | biostudies-literature
Project description:Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity, however, the mechanism remains unknown. In this study, we hypothesized that the ultrafine fraction of ambient pollutant particles would cause endothelial cells dysfunction. We profiled gene expression of human pulmonary artery endothelial cells (HPAEC) exposed to ultrafine Chapel Hill particles (UFP) (100μg/ml) or vehicle for 4h with Affymetrix HG U133 Plus 2.0 chips (N = 4 each). Using an unpaired t-test (p <0.01, 5% false discovery rate) we found 426 unique genes to be differentially expressed with 320 upregulated genes and 106 downregulated genes. Among these genes, we noted upregulation of genes related to coagulation-inflammation circuitry including tissue factor (F3), coagulation factor II receptor-like 2 (F2RL2, PAR3), interleukin (IL)-6 and IL-8. Upregulation of these genes were independently confirmed by RT-PCR and/or protein release. Genes related to the CXC chemokine family that have been implicated in the pathogenesis of vascular disease were upregulated, including MCP-1 (2.60 fold), IL-8 (2.47 fold), CXCL1 (1.41 fold), CXCL2 (1.95 fold), CXCL3 (2.28 fold) and CXCR4 (1.30 fold). In addition, genes related to clotting independent signaling of F3 were also differentially expressed, including FOS, JUN and NFKBIA. Treatment of HPAEC with UFP for 16 hours increased the release of IL6 and IL8 by 1.9-fold and 1.8-fold respectively. Pretreatment of HPAEC with a blocking antibody against F3 attenuated IL6 and IL8 release by 30% and 70% respectively. Thus using gene profiling, we uncovered that UFP may induce vascular endothelial cells to express genes related to clotting and angiogenesis. These results provide a novel hypothesis that PM may cause cardiovascular adverse health effects via induction of tissue factor in vascular endothelial cells which then triggers clotting dependent and independent downstream signaling. Keywords: particle treatment
2007-01-26 | GSE4567 | GEO
Project description:Introduction:Particulate matter (PM) and cigarette-related cadmium exposure increases inflammation and smokers' susceptibility to developing lung diseases. The majority of inhaled metals are attached to the surface of ultrafine particles (UFPs). A low inhaled UFP content in exhaled breath condensate (EBC) reflects a high inflammatory status of airways. Methods:EBC was collected from 58 COPD patients and 40 healthy smokers and nonsmokers. Participants underwent spirometry, diffusion capacity, EBC and blood sampling. Environmental pollution data were collected from monitoring stations. UFPs were measured in EBC and serum, and cadmium content was quantified. Results:Subjects with low UFP concentrations in EBC (<0.18×108·mL-1) had been exposed to higher long-term PM2.5 levels versus subjects with high UFP concentrations in EBC (>0.18×108·mL-1) (21.9 µg·m-3 versus 17.4 µg·m-3, p?0.001). Long-term PM2.5 exposure levels correlated negatively with UFP concentrations in EBC and positively with UFP concentrations in serum (r=-0.54, p?0.001 and r=0.23, p=0.04, respectively). Healthy smokers had higher cadmium levels in EBC versus healthy nonsmokers and COPD patients (25.2 ppm versus 23.7 ppm and 23.3 ppm, p=0.02 and p=0.002, respectively). Subjects with low UFP concentrations in EBC also had low cadmium levels in EBC versus subjects with high UFP levels (22.8 ppm versus 24.2 ppm, p=0.004). Conclusions:Low UFP concentration in EBC is an indicator of high-level PM exposure. High cadmium levels in EBC among smokers and the association between cadmium and UFP content in EBC among COPD patients indicate cadmium lung toxicity.
| S-EPMC7487350 | biostudies-literature
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| S-EPMC1852686 | biostudies-literature
Project description:BACKGROUND:Epidemiological evidence on the health effects of ultrafine particles (UFP) remains insufficient to infer a causal relationship that is largely due to different size ranges and exposure metrics examined across studies. Moreover, evidence regarding the association between UFP and cardiovascular disease at a sub-daily timescale is lacking. OBJECTIVE:We investigated the relationship between different particle metrics, including particle number (PNC), length (PLC), and surface area (PSC) concentrations, and myocardial infarction (MI) at an hourly timescale. METHODS:We collected hourly air pollution and meteorological data from fixed urban background monitoring sites and hourly nonfatal MI cases from a MI registry in Augsburg, Germany, during 2005-2015. We conducted a time-stratified case-crossover analysis with conditional logistic regression to estimate the association between hourly particle metrics and MI cases, adjusted for air temperature and relative humidity. We also examined the independent effects of a certain particle metric in two-pollutant models by adjusting for copollutants, including particulate matter (PM) with an aerodynamic diameter of ?10?m or 2.5?m (PM10 and PM2.5, respectively), nitrogen dioxide, ozone, and black carbon. RESULTS:Overall, a total of 5,898 cases of nonfatal MI cases were recorded. Exploratory analyses showed similar associations across particle metrics in the first 6-12 h. For example, interquartile range increases in PNC within the size range of 10-100?nm, PLC, and PSC were associated with an increase of MI 6 h later by 3.27% [95% confidence interval (CI): 0.27, 6.37], 5.71% (95% CI: 1.79, 9.77), and 5.84% (95% CI: 1.04, 10.87), respectively. Positive, albeit imprecise, associations were observed for PNC within the size range of 10-30?nm and 100-500?nm. Effect estimates for PLC and PSC remained similar after adjustment for PM and gaseous pollutants. CONCLUSIONS:Transient exposure to particle number, length, and surface area concentrations or other potentially related exposures may trigger the onset of nonfatal myocardial infraction. https://doi.org/10.1289/EHP5478.
| S-EPMC7015564 | biostudies-literature
Project description:BackgroundThe metabolomic signatures of short- and long-term exposure to PM2.5 have been reported and linked to inflammation and oxidative stress. However, little is known about the relative contribution of the specific PM2.5 species (hence sources) that drive these metabolomic signatures.ObjectivesWe aimed to determine the relative contribution of the different species of PM2.5 exposure to the perturbed metabolic pathways related to changes in the plasma metabolome.MethodsWe performed mass-spectrometry based metabolomic profiling of plasma samples among men from the Normative Aging Study to identify metabolic pathways associated with PM2.5 species. The exposure windows included short-term (one, seven-, and thirty-day moving average) and long-term (one year moving average). We used linear mixed-effect regression with subject-specific intercepts while simultaneously adjusting for PM2.5, NO2, O3, temperature, relative humidity, and covariates and correcting for multiple testing. We also used independent component analysis (ICA) to examine the relative contribution of patterns of PM2.5 species.ResultsBetween 2000 and 2016, 456 men provided 648 blood samples, in which 1158 metabolites were quantified. We chose 305 metabolites for the short-term and 288 metabolites for the long-term exposure in this analysis that were significantly associated (p-value < 0.01) with PM2.5 to include in our PM2.5 species analysis. On average, men were 75.0 years old and their body mass index was 27.7 kg/m2. Only 3% were current smokers. In the adjusted models, ultrafine particles (UFPs) were the most significant species of short-term PM2.5 exposure followed by nickel, vanadium, potassium, silicon, and aluminum. Black carbon, vanadium, zinc, nickel, iron, copper, and selenium were the significant species of long-term PM2.5 exposure. We identified several metabolic pathways perturbed with PM2.5 species including glycerophospholipid, sphingolipid, and glutathione. These pathways are involved in inflammation, oxidative stress, immunity, and nucleic acid damage and repair. Results were overlapped with the ICA.ConclusionsWe identified several significant perturbed plasma metabolites and metabolic pathways associated with exposure to PM2.5 species. These species are associated with traffic, fuel oil, and wood smoke. This is the largest study to report a metabolomic signature of PM2.5 species' exposure and the first to use ICA.
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Project description:The selective recovery of ultrafine, <10 μm, particles remains a significant challenge in the minerals industry. Indeed, these particles often report to tailings impoundments, resulting in under-utilization of mined resources and the need for tailings dams. Recently, a technique has been developed offering the potential to selectively recover particles down to <1 μm in size. This technique, originally inspired by oil agglomeration, uses a high internal-phase water in oil emulsion as a binder to selectively agglomerate hydrophobic particles. Due to the significant concentration of the dispersed aqueous phase, ~95%, the continuous organic phase forms a network of very thin, permeable films, estimated to be 60 nm thick. These are stabilized by an emulsifier. In the high shear field of the agglomeration process, the binder is fragmented into smaller hydrophobic portions, delivering its thin film coating to the adhering hydrophobic particles. Permeation of water across the thin films eliminates the viscous hydrodynamic resistance, permitting sub-micron particle recovery to occur at rates similar to those for particles considerably larger in size. This recovery occurs within seconds under intense mixing. In this study, a model system consisting of magnetite, with a Sauter mean diameter of 11.4 μm, was agglomerated using the water in oil emulsion binder. The binder, which contained the emulsifier sorbitan monooleate, appeared to also act as a collector for the magnetite, thus no separate particle conditioning step was required. Curiously, however, the binder requirements were higher than expected. Further investigations concerning the stability of the binder revealed that the magnetite particles were causing rapid binder degradation. Therefore, prior to agglomeration using the binder, the particles were conditioned with sorbitan monooleate to render them hydrophobic. This pre-conditioning led to significant reductions in the binder dosage required to achieve agglomeration. Moreover, the resulting dosage matched that predicted by a model silica system for the same specific hydrophobic surface area, thus allowing a model to be validated based on the required binder dosage for a known hydrophobic surface area. Examination of binder stability in the presence of conditioned magnetite revealed that the now hydrophobic particles stabilized the binder.
| S-EPMC6018405 | biostudies-literature
Project description:RationaleForkhead box-O transcription factors (FoxOs) transduce a wide range of extracellular signals, resulting in changes in cell survival, cell cycle progression, and several cell type-specific responses. FoxO1 is expressed in many cell types, including endothelial cells (ECs). Previous studies have shown that Foxo1 knockout in mice results in embryonic lethality at E11 because of impaired vascular development. In contrast, somatic deletion of Foxo1 is associated with hyperproliferation of ECs. Thus, the precise role of FoxO1 in the endothelium remains enigmatic.ObjectiveTo determine the effect of endothelial-specific knockout and overexpression of FoxO1 on vascular homeostasis.Methods and resultsWe show that EC-specific disruption of Foxo1 in mice phenocopies the full knockout. Although endothelial expression of FoxO1 rescued otherwise Foxo1-null animals, overexpression of constitutively active FoxO1 resulted in increased EC size, occlusion of capillaries, elevated peripheral resistance, heart failure, and death. Knockdown of FoxO1 in ECs resulted in marked inhibition of basal and vascular endothelial growth factor-induced Akt-mammalian target of rapamycin complex 1 (mTORC1) signaling.ConclusionsOur findings suggest that in mice, endothelial expression of FoxO1 is both necessary and sufficient for embryonic development. Moreover, FoxO1-mediated feedback activation of Akt maintains growth factor responsive Akt/mTORC1 activity within a homeostatic range.
| S-EPMC4961050 | biostudies-literature
Project description:BACKGROUND:Exposure to ultrafine particles (UFP, particles with aerodynamic diameter?<?100?nm) is associated with reduced lung function and airway inflammation in individuals with asthma. Recently, elevated UFP number concentrations (PN) from aircraft landing and takeoff activity were identified downwind of the Los Angeles International Airport (LAX) but little is known about the health impacts of airport-related UFP exposure. METHODS:We conducted a randomized crossover study of 22 non-smoking adults with mild to moderate asthma in Nov-Dec 2014 and May-Jul 2015 to investigate short-term effects of exposure to LAX airport-related UFPs. Participants conducted scripted, mild walking activity on two occasions in public parks inside (exposure) and outside (control) of the high UFP zone. Spirometry, multiple flow exhaled nitric oxide, and circulating inflammatory cytokines were measured before and after exposure. Personal UFP PN and lung deposited surface area (LDSA) and stationary UFP PN, black carbon (BC), particle-bound PAHs (PB-PAH), ozone (O3), carbon dioxide (CO2) and particulate matter (PM2.5) mass were measured. Source apportionment analysis was conducted to distinguish aircraft from roadway traffic related UFP sources. Health models investigated within-subject changes in outcomes as a function of pollutants and source factors. RESULTS:A high two-hour walking period average contrast of ~34,000?particles·cm-3 was achieved with mean (std) PN concentrations of 53,342 (25,529) and 19,557 (11,131)?particles·cm-3 and mean (std) particle size of 28.7 (9.5) and 33.2 (11.5) at the exposure and control site, respectively. Principal components analysis differentiated airport UFPs (PN), roadway traffic (BC, PB-PAH), PM mass (PM2.5, PM10), and secondary photochemistry (O3) sources. A standard deviation increase in the 'Airport UFPs' factor was significantly associated with IL-6, a circulating marker of inflammation (single-pollutant model: 0.21, 95% CI?=?0.08-0.34; multi-pollutant model: 0.18, 0.04-0.32). The 'Traffic' factor was significantly associated with lower Forced Expiratory Volume in 1?s (FEV1) (single-pollutant model: -1.52, -2.28 to -0.77) and elevated sTNFrII (single-pollutant model: 36.47; 6.03-66.91; multi-pollutant model: 64.38; 6.30-122.46). No consistent associations were observed with exhaled nitric oxide. CONCLUSIONS:To our knowledge, our study is the first to demonstrate increased acute systemic inflammation following exposure to airport-related UFPs. Health effects associated with roadway traffic exposure were distinct. This study emphasizes the importance of multi-pollutant measurements and modeling techniques to disentangle sources of UFPs contributing to the complex urban air pollution mixture and to evaluate population health risks.
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