School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai 200032, China.
School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Fudan University, Shanghai 200032, China.
Environ Int. 2016 Sep;94:661-666. doi: 10.1016/j.envint.2016.07.001. Epub 2016 Jul 7.
The underlying intermediate mechanisms about the association between fine particulate matter (PM2.5) air pollution and blood pressure (BP) were unclear. Few epidemiological studies have explored the potential mediation effects of angiotensin-converting enzyme (ACE) and its DNA methylation.
We designed a longitudinal panel study with 4 follow-ups among 36 healthy college students in Shanghai, China from December 17, 2014 to July 11, 2015. We measured personal real-time exposure to PM2.5, serum ACE level, and blood methylation of ACE gene and the repetitive elements. We applied linear mixed-effects models to examine the effects of PM2.5 on ACE protein, DNA methylation and BP markers. Furthermore, we conducted mediation analyses to evaluate the potential pathways.
An interquartile range increase (26.78μg/m(3)) in 24-h average exposure to PM2.5 was significantly associated with 1.12 decreases in ACE average methylation (%5mC), 13.27% increase in ACE protein, and increments of 1.13mmHg in systolic BP, 0.66mmHg in diastolic BP and 0.82mmHg in mean arterial pressure. ACE hypomethylation mediated 11.78% (P=0.03) of the elevated ACE protein by PM2.5. Increased ACE protein accounted for 3.9013.44% (P=0.350.68) of the elevated BP by PM2.5. Repetitive-element methylation was also decreased but did not significantly mediate the association between PM2.5 and BP.
This investigation provided strong evidence that short-term exposure to PM2.5 was significantly associated with BP, ACE protein and ACE methylation. Our findings highlighted a possible involvement of ACE and ACE methylation in the effects of PM2.5 on elevating BP.
细颗粒物（PM2.5）空气污染与血压（BP）之间关联的潜在中间机制尚不清楚。少数流行病学研究探讨了血管紧张素转换酶（ACE）及其 DNA 甲基化的潜在中介效应。
我们设计了一项在中国上海的 36 名健康大学生的 4 次随访的纵向面板研究，时间为 2014 年 12 月 17 日至 2015 年 7 月 11 日。我们测量了个人实时暴露于 PM2.5、血清 ACE 水平以及 ACE 基因和重复元件的血液甲基化。我们应用线性混合效应模型来检验 PM2.5 对 ACE 蛋白、DNA 甲基化和 BP 标志物的影响。此外，我们进行了中介分析以评估潜在的途径。
24 小时平均 PM2.5 暴露增加一个四分位距（26.78μg/m3），ACE 平均甲基化（%5mC）减少 1.12%，ACE 蛋白增加 13.27%，收缩压增加 1.13mmHg，舒张压增加 0.66mmHg，平均动脉压增加 0.82mmHg。ACE 低甲基化介导了 PM2.5 引起的 ACE 蛋白升高的 11.78%（P=0.03）。增加的 ACE 蛋白占 PM2.5 引起的 BP 升高的 3.90%13.44%（P=0.350.68）。重复元件甲基化也降低了，但与 PM2.5 和 BP 之间的关联没有显著关系。
本研究提供了强有力的证据表明，短期暴露于 PM2.5 与 BP、ACE 蛋白和 ACE 甲基化显著相关。我们的发现强调了 ACE 和 ACE 甲基化可能参与了 PM2.5 升高 BP 的作用。
