Effects of Air Pollution and Blood Mitochondrial DNA Methylation on Markers of Heart Rate Variability.

BACKGROUND: The mitochondrion is the primary target of oxidative stress in response to exogenous environments. Mitochondrial DNA (mtDNA) is independent from nuclear DNA and uses separate epigenetic machinery to regulate mtDNA methylation. The mtDNA damage induced by oxidative stress can cause mitochondrial dysfunction and is implicated in human diseases; however, mtDNA methylation has been largely overlooked in environmental studies relating to human disease. The purpose of this study was to examine the association between exposure to fine metal-rich particulates (particulate matter <2.5 µm in diameter [PM2.5]) from welding in a boilermaker union and blood mtDNA methylation in relation to heart rate variability. METHODS AND RESULTS: Forty-eight healthy men were recruited on multiple sampling cycles at the Boilermaker Union Local 29, located in Quincy, Massachusetts. We measured personal PM2.5 in the background ambient environment. We measured blood mtDNA methylation in the mtDNA promoter (D-loop) and genes essential for ATP synthesis (MT-TF and MT-RNR1) by bisulfite pyrosequencing. All analyses were adjusted for demographics, type of job, season, welding-work day, and mtDNA methylation experimental batch effect. The participants' PM2.5 exposure was significantly higher after a welding-work day (mean 0.38 mg/m(3)) than the background personal level (mean 0.15 mg/m(3), P<0.001). Blood mtDNA methylation in the D-loop promoter was associated with PM2.5 levels (ß=-0.99%, SE=0.41, P=0.02). MT-TF and MT-RNR1 methylation was not associated with PM2.5 exposure (ß=0.10%, SE=0.45, P=0.82). Interaction of PM2.5 exposure levels and D-loop promoter methylation was significantly associated with markers of heart rate variability. CONCLUSIONS: Blood mtDNA methylation levels were negatively associated with PM2.5 exposure and modified the adverse relationships between PM2.5 exposure and heart rate variability outcomes.

Long-Term Metal PM2.5 Exposures Decrease Cardiac Acceleration and Deceleration Capacities in Welders.

OBJECTIVE: The aim of the study was to clarify whether long-term metal particulates affect cardiac acceleration capacity (AC), deceleration capacity (DC), or both. METHODS: We calculated chronic exposure index (CEI) for PM2.5 over the work life of 50 boilermakers and obtained their resting AC and DC. Linear regression was used to assess the associations between CEI PM2.5 exposure and each of AC and DC, controlling for age, acute effects of welding exposure, and diurnal variation. RESULTS: Mean (standard deviation) CEI for PM2.5 exposure was 1.6 (2.4) mg/m-work years and ranged from 0.001 to 14.6 mg/m-work years. In our fully adjusted models, a 1 mg/m-work year increase in CEI for PM2.5 was associated with a decrease of 1.03 (95% confidence interval: 0.10, 1.96) ms resting AC, and a decrease of 0.67 (95% confidence interval: -0.14, 1.49) ms resting DC. CONCLUSIONS: Long-term metal particulate exposures decrease cardiac accelerations and decelerations.

The relationship between occupational metal exposure and arterial compliance.

BACKGROUND: The objective of this study was to evaluate the relationship between cumulative occupational exposure to various metals and arterial compliance in welders. METHODS: The observational follow-up study consisted of 25 subjects. Levels of nickel (Ni), lead, cadmium, manganese, and arsenic from toenails were assessed using mass spectrometry. Arterial compliance as reflected by augmentation index (AIx) was measured using SphygmoCor Px Pulse Wave Analysis System. Linear regression models were used to assess the associations. RESULTS: For every 1 unit increase in log-transformed toenail Ni, there was a statistically significant 5.68 (95% confidence interval, 1.38 to 9.98; P = 0.01) unit increase in AIx. No significant associations were found between AIx and lead, cadmium, manganese, and arsenic. CONCLUSIONS: Cumulative Ni exposure is associated with increased arterial stiffness in welders and may increase risk of adverse cardiovascular outcomes.

Heart rate variability and DNA methylation levels are altered after short-term metal fume exposure among occupational welders: a repeated-measures panel study.

BACKGROUND: In occupational settings, boilermakers are exposed to high levels of metallic fine particulate matter (PM2.5) generated during the welding process. The effect of welding PM2.5 on heart rate variability (HRV) has been described, but the relationship between PM2.5, DNA methylation, and HRV is not known. METHODS: In this repeated-measures panel study, we recorded resting HRV and measured DNA methylation levels in transposable elements Alu and long interspersed nuclear element-1 (LINE-1) in peripheral blood leukocytes under ambient conditions (pre-shift) and right after a welding task (post-shift) among 66 welders. We also monitored personal PM2.5 level in the ambient environment and during the welding procedure. RESULTS: The concentration of welding PM2.5 was significantly higher than background levels in the union hall (0.43 mg/m3 vs. 0.11 mg/m3, p < 0.0001). The natural log of transformed power in the high frequency range (ln HF) had a significantly negative association with PM2.5 exposure (ß = -0.76, p = 0.035). pNN10 and pNN20 also had a negative association with PM2.5 exposure (ß = -0.16%, p = 0.006 and ß = -0.13%, p = 0.030, respectively). PM2.5 was positively associated with LINE-1 methylation [ß = 0.79%, 5-methylcytosince (%mC), p = 0.013]; adjusted for covariates. LINE-1 methylation did not show an independent association with HRV. CONCLUSIONS: Acute decline of HRV was observed following exposure to welding PM2.5 and evidence for an epigenetic response of transposable elements to short-term exposure to high-level metal-rich particulates was reported.

Global metabolomic profiling reveals an association of metal fume exposure and plasma unsaturated fatty acids.

BACKGROUND: Welding-associated air pollutants negatively affect the health of exposed workers; however, their molecular mechanisms in causing disease remain largely unclear. Few studies have systematically investigated the systemic toxic effects of welding fumes on humans. OBJECTIVES: To explore the effects of welding fumes on the plasma metabolome, and to identify biomarkers for risk assessment of welding fume exposure. METHODS: The two-stage, self-controlled exploratory study included 11 boilermakers from a 2011 discovery panel and 8 boilermakers from a 2012 validation panel. Plasma samples were collected pre- and post-welding fume exposure and analyzed by chromatography/mass spectrometry. RESULTS: Eicosapentaenoic or docosapentaenoic acid metabolic changes post-welding were significantly associated with particulate (PM2.5) exposure (p<0.05). The combined analysis by linear mixed-effects model showed that exposure was associated with a statistically significant decline in metabolite change of eicosapentaenoic acid [ß(95% CI) = -0.013(-0.022 ≈ -0.004); p = 0.005], docosapentaenoic acid n3 [ß(95% CI) = -0.010(-0.018 ≈ -0.002); p = 0.017], and docosapentaenoic acid n6 [ß(95% CI) = -0.007(-0.013 ≈ -0.001); p = 0.021]. Pathway analysis identified an association of the unsaturated fatty acid pathway with exposure (p Study-2011 = 0.025; p Study-2012 = 0.021; p Combined = 0.009). The functional network built by these fatty acids and their interactive genes contained significant enrichment of genes associated with various diseases, including neoplasms, cardiovascular diseases, and lipid metabolism disorders. CONCLUSIONS: High-dose exposure of metal welding fumes decreases unsaturated fatty acids with an exposure-response relationship. This alteration in fatty acids is a potential biological mediator and biomarker for exposure-related health disorders.