DNA hypomethylation, ambient particulate matter, and increased blood pressure: findings from controlled human exposure experiments.
DNA hypomethylation, ambient particulate matter, and increased blood pressure: findings from controlled human exposure experiments.
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DOI：
10.1161/jaha.113.000212
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发表时间：
2013-06-19
影响因子：
5.4
通讯作者：
Baccarelli AA
中科院分区：
文献类型：
--
作者：
Bellavia A;Urch B;Speck M;Brook RD;Scott JA;Albetti B;Behbod B;North M;Valeri L;Bertazzi PA;Silverman F;Gold D;Baccarelli AA
在受控人体暴露和社区研究中，短期暴露于细小（<2.5 μm 空气动力学直径）环境颗粒物 (PM) 与血压 (BP) 升高有关。然而，粗颗粒（2.5 至 10 μm）PM 暴露是否会增加血压尚不确定。最近的观察性研究将 PM 暴露与血液 DNA 低甲基化联系起来，这是一种激活炎症和血管反应的表观遗传改变。 No experimental evidence is available to confirm those observational data and demonstrate the relations between PM, hypomethylation, and BP. We conducted a cross‐over trial of controlled‐human exposure to concentrated ambient particles (CAPs). 15 名健康成年参与者按随机顺序暴露于细 CAP、粗 CAP 或 HEPA 过滤的医用空气（对照）中 130 分钟，清洗时间≥2 周。在暴露前和暴露后测量重复元件（Alu、长散布核元件-1 [LINE-1]）和候选基因（TLR4、IL-12、IL-6、iNOS）血液甲基化、收缩压和舒张压。经过多重比较调整后，精细的 CAP 暴露降低了 Alu 甲基化（β-标准化=-0.74，调整后-P=0.03）；粗 CAP 暴露降低了 TLR4 甲基化（β-标准化=-0.27，调整后-P=0.04）。精细和粗略 CAP 均测定收缩压显着升高（分别为 β=2.53 mm Hg，P=0.001；β=1.56 mm Hg，P=0.03）和舒张压无显着升高（分别为 β=0.98 mm Hg，P=0.12；β=0.82 mm Hg，P=0.11）。 Alu 和 TLR4 甲基化降低与暴露后 DBP 升高相关（分别为 β 标准化 = 0.41，P = 0.04；β 标准化 = 0.84，P = 0.02）。 Decreased TLR4 methylation was associated with higher postexposure SBP (β‐standardized=1.45, P=0.01). 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.
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. 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). 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.