Extracellular vesicle-enriched microRNAs interact in the association between long-term particulate matter and blood pressure in elderly men.,Environmental Research

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Extracellular vesicle-enriched microRNAs interact in the association between long-term particulate matter and blood pressure in elderly men.
Environmental Research ( IF 8.3 ) Pub Date : 2018-09-05 , DOI: 10.1016/j.envres.2018.09.002
Rodosthenis S Rodosthenous ₁ , Itai Kloog ₂ , Elena Colicino ₃ , Jia Zhong ₄ , Luis A Herrera ₅ , Pantel Vokonas ₆ , Joel Schwartz ₄ , Andrea A Baccarelli ₇ , Diddier Prada ₈

Affiliation

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, 665 Huntington Ave, Boston, MA 02115, United States; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, United States.
Department of Geography and Environmental Development, Ben-Gurion University of the Negev, 663 Beer Sheva, Israel.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, 665 Huntington Ave, Boston, MA 02115, United States; Icahn School of Medicine, Mount Sinai Hospital, 1 Gustave L. Levy Place, New York, NY 10029-5674, United States.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, 665 Huntington Ave, Boston, MA 02115, United States.
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología - Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 14080, Mexico.
Veterans Affairs Boston Healthcare System, 150 South Huntington Ave, Boston, MA 02130, United States; Department of Epidemiology, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, United States; Department of Medicine, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, United States.
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, United States.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, 665 Huntington Ave, Boston, MA 02115, United States; Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología - Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 14080, Mexico.

Background

Several studies have shown that exposure to particulate matter (PM) may lead to increased systemic blood pressure, but the underlying biological mechanisms remain unknown. Emerging evidence shows that extracellular vesicle-enriched miRNAs (evmiRNAs) are associated with PM exposure and cardiovascular risk. In this study, we investigated the role of evmiRNAs in the association between PM and blood pressure, as well as their epigenetic regulation by DNA methylation.

Methods

Participants (n = 22, men) were randomly selected from the Veterans Affairs Normative Aging Study (NAS). Long-term (1-year and 6-month average) PM_2.5 exposure was estimated at 1 × 1-km resolution using spatio-temporal prediction models and BC was estimated using validated time varying land use regression models. We analyzed 31 evmiRNAs detected in ≥ 90% of all individuals and for statistical analysis, we used mixed effects models with random intercept adjusted for age, body mass index, smoking, C-reactive protein, platelets, and white blood cells.

Results

We found that per each 2-standard deviations increase in 6-month PM_2.5 ambient levels, there was an increase in 0.19 mm Hg (95% Confidence Interval [95%CI]: 0.11, 0.28 mmHg; p < 0.001) in systolic blood pressure (SBP). Per each 2-standard deviations increase in 1-year PM_2.5 levels, there was an increase in 0.11 mm Hg (95% Confidence Interval [95% CI]: 0.03, 0.19 mmHg; p = 0.012) in SBP in older male individuals. We also found that both miR-199a/b (β = 6.13 mmHg; 95% CI: 0.87, 11.39; p_interaction = 0.07) and miR-223–3p (β = 30.17 mmHg; 95% CI: 11.96, 48.39 mmHg; p_interaction = 0.01) modified the association between 1-year PM_2.5 and SBP. When exploring DNA methylation as a potential mechanism that could epigenetically regulate expression of evmiRNAs, we found that PM_2.5 ambient levels were negatively associated with DNA methylation levels at CpG (cg23972892) near the enhancer region of miR-199a/b (β = −13.11; 95% CI: −17.70, −8.52; p_Bonferroni< 0.01), but not miR-223-3p.

Conclusions

Our findings suggest that expression of evmiRNAs may be regulated by DNA methylation in response to long-term PM_2.5 ambient levels and modify the magnitude of association between PM_2.5 and systolic blood pressure in older individuals.

中文翻译：

胞外富含囊泡的microRNA在老年人中长期颗粒物与血压之间的关联中相互作用。

背景

几项研究表明，暴露于颗粒物（PM）可能会导致全身血压升高，但其潜在的生物学机制仍然未知。新兴证据表明，细胞外富含囊泡的miRNA（evmiRNA）与PM暴露和心血管风险相关。在这项研究中，我们调查了evmiRNA在PM和血压之间的关联中的作用，以及它们通过DNA甲基化的表观遗传调控。

方法

参与者（n = 22，男性）是从退伍军人事务规范性老龄化研究（NAS）中随机选择的。使用时空预测模型以1×1 km分辨率估算长期（平均1年和6个月）PM _2.5暴露，并使用经过验证的时变土地利用回归模型估算BC。我们分析了在≥90％的所有个体中检测到的31种evmiRNA，并进行了统计分析，我们使用了混合效应模型，并根据年龄，体重指数，吸烟，C反应蛋白，血小板和白细胞对随机截距进行了调整。

结果

我们发现，在6个月的PM _2.5环境水平中，每2个标准差的增加，收缩期血液中的0.19 mm Hg升高（95％置信区间[95％CI]：0.11，0.28 mmHg； p <0.001）压力（SBP）。1年PM _2.5水平每升高2个标准差，老年男性个体的SBP升高0.11 mm Hg（95％置信区间[95％CI]：0.03，0.19 mmHg; p = 0.012）。我们还发现，miR-199a / b（β= 6.13 mmHg； 95％CI：0.87，11.39 ； p_相互作用= 0.07）和miR-223-3p（β= 30.17 mmHg； 95％CI：11.96，48.39 mmHg；β= 30.17 mmHg； 95％CI：11.96，48.39 mmHg； p_互动= 0.01）修改了1年PM _2.5之间的关联和SBP。当探索DNA甲基化作为可能表观遗传调控evmiRNAs表达的潜在机制时，我们发现PM _2.5环境水平与miR-199a / b增强子区域附近CpG（cg23972892）的DNA甲基化水平呈负相关（β= -13.11 ； 95％CI：-17.70，−8.52； p _Bonferroni <0.01），但未检测到miR-223-3p。