title: DNA hypomethylation, ambient particulate matter, and increased blood pressure: findings from controlled human exposure experiments.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA 02215, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bellavia
authors.forename: Bruce
authors.initials: B
authors.lastname: Urch
authors.forename: Mary
authors.initials: M
authors.lastname: Speck
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brook
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Scott
authors.forename: Benedetta
authors.initials: B
authors.lastname: Albetti
authors.forename: Behrooz
authors.initials: B
authors.lastname: Behbod
authors.forename: Michelle
authors.initials: M
authors.lastname: North
authors.forename: Linda
authors.initials: L
authors.lastname: Valeri
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Frances
authors.initials: F
authors.lastname: Silverman
authors.forename: Diane
authors.initials: D
authors.lastname: Gold
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D018592:Cross-Over Studies; D019175:DNA Methylation; D004311:Double-Blind Method; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D052638:Particulate Matter
keywords: DNA methylation; air pollution; blood pressure; epigenetics; mediation