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

Journal of the American Heart Association - Tập 2 Số 3 - 2013
Andrea Bellavia1, Bruce Urch2,3, Mary Speck2,3, Robert D. Brook4, Jeremy A. Scott2,3, Benedetta Albetti5, Behrooz Behbod1, Michelle L. North2,3, Linda Valeri6, Pier Alberto Bertazzi5, Frances Silverman2,3, Diane R. Gold7,1, Andrea Baccarelli1
1Department of Environmental Health, Harvard School of Public Health, Boston, MA
2Division of Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
3Gage Occupational and Environmental Health Unit, St. Michael's Hospital, Toronto, Ontario, Canada
4Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI
5Department of Occupational and Environmental Health, Universita' degli Studi di Milano and Fondazione Ca' Granda Policlinico, Milan, Italy
6Department of Biostatistics, Harvard School of Public Health, Boston, MA
7Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

Tóm tắt

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 ( CAP s). Fifteen healthy adult participants were exposed for 130 minutes to fine CAP s, coarse CAP s, 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 CAP s exposure lowered Alu methylation (β‐standardized=−0.74, adjusted‐ P =0.03); coarse CAP s exposure lowered TLR4 methylation (β‐standardized=−0.27, adjusted‐ P =0.04). Both fine and coarse CAP s 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 .

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Journal of the American Heart Association

Tập 2 Số 3

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