Fine particulate matter air pollution plus ozone impairs vascular function and raises diastolic blood pressure. We aimed to determine the mechanism and air pollutant responsible. The effects of pollution on heart rate variability, blood pressure, biomarkers, and brachial flow-mediated dilatation were determined in 2 randomized, double-blind, cross-over studies. In Ann Arbor, 50 subjects were exposed to fine particles (150 μg/m3) + ozone (120 ppb) for 2 hours on 3 occasions with pretreatments of an endothelin antagonist (Bosentan 250 mg), anti-oxidant (Vitamin C 2 g), or placebo. In Toronto, 31 subjects were exposed to 4 different conditions (particles + ozone, particles, ozone, and filtered air). In Toronto, diastolic blood pressure significantly increased (2.9 and 3.6 mm Hg) only during particle-containing exposures in association with particulate matter concentration and reductions in heart rate variability. Flow-mediated dilatation significantly decreased (2.0 and 2.9%) only 24 hours after particle-containing exposures in association with particulate matter concentration and increases in blood tumor necrosis factor-alpha. In Ann Arbor, diastolic blood pressure significantly similarly increased during all exposures (2.5 - 4.0 mm Hg), a response not mitigated by pretreatments. Flow-mediated dilatation remained unaltered. Particulate matter, not ozone, was responsible for increasing diastolic blood pressure during air pollution inhalation most plausibly by instigating acute autonomic imbalance. Only particles from urban Toronto additionally impaired endothelial function likely via slower proinflammatory pathways. Our findings demonstrate credible mechanisms whereby fine particulate matter could trigger acute cardiovascular events and that aspects of exposure location may be an important determinant of the health consequences.

BackgroundShort‐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 ResultsWe 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).ConclusionsOur 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.

Acute exposure to fine particle (PM) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM (250 μg/m) under placebo, and PM (250 μg/m) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B, and 1 mg/d vitamin B), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4 T-helper cells. PM induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM effect by 102% ( = 0.01). Our study indicates that individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM effects, with possible significant public health benefit in areas with frequent PM peaks.