title: Personal exposure to fine particulate matter and blood pressure: A role of angiotensin converting enzyme and its DNA methylation.
abstract: 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 3.90~13.44% (P=0.35~0.68) 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.
authors.affiliation: 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.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Jingjin
authors.initials: J
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: JC School of Public Health and Primary Care, Prince of Wales Hospital, Sha Tin, N.T., Hong Kong SAR, China.
authors.forename: Lap Ah
authors.initials: LA
authors.lastname: Tse
authors.affiliation: 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.
authors.forename: Huichu
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Zhijing
authors.initials: Z
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Xia
authors.initials: X
authors.lastname: Meng
authors.affiliation: 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.
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yue
authors.initials: Y
authors.lastname: Niu
authors.affiliation: 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.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Xia
authors.affiliation: 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.
authors.forename: Zhuohui
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: 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. Electronic address: kanh@fudan.edu.cn.
authors.forename: Haidong
authors.initials: H
authors.lastname: Kan
mesh_terms: D000393:Air Pollutants / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D002681:China; D019175:DNA Methylation / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D019570:Inhalation Exposure / Q000009:adverse effects / Q000032:analysis*; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis* / Q000633:toxicity; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D052638:Particulate Matter; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: Angiotensin-converting enzyme; Blood pressure; DNA methylation; Fine particulate matter; Panel study