TY - JOUR
T1 - DNA hypomethylation, ambient particulate matter, and increased blood pressure
T2 - Findings from controlled human exposure experiments
AU - Bellavia, Andrea
AU - Urch, Bruce
AU - Speck, Mary
AU - Brook, Robert D.
AU - Scott, Jeremy A.
AU - Albetti, Benedetta
AU - Behbod, Behrooz
AU - North, Michelle
AU - Valeri, Linda
AU - Bertazzi, Pier Alberto
AU - Silverman, Frances
AU - Gold, Diane
AU - Baccarelli, Andrea A.
PY - 2013/9/4
Y1 - 2013/9/4
N2 - 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 (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 candidategene (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.
AB - 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 (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 candidategene (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.
KW - Air pollution
KW - Blood pressure
KW - DNA methylation
KW - Epigenetics
KW - Mediation
UR - http://www.scopus.com/inward/record.url?scp=84885859371&partnerID=8YFLogxK
U2 - 10.1161/JAHA.113.000212
DO - 10.1161/JAHA.113.000212
M3 - Article
C2 - 23782920
AN - SCOPUS:84885859371
SN - 2047-9980
VL - 2
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 3
M1 - e000212
ER -