Personal Ozone Exposure, Blood Pressure and Vascular Endothelial Function: A Panel Study Based on Cytokines, DNA Methylation and Metabolomics

摘要

Background: Epidemiological studies have reported inconsistent findings on the cardiovascular effects of exposure to ambient ozone. There is a lack of molecular epidemiological studies of ozone based on personal real-time monitoring. Objective: To explore the impacts of personal ozone exposure on blood pressure and vascular endothelial function. Methods: We conducted a longitudinal panel study with 4 follow-ups among 40 college students in Shanghai, China, during the warm period of 2016. We measured in real time personal ozone exposure levels and serum angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1), locus-specific methylation of ACE and ET-1. We also used an untargeted metabolomic approach to systemically evaluate the vascular effects of ozone. We applied linear mixed-effects models to examine the effects of ozone on blood pressure (BP), ACE, ET-1, DNA methylation and metabolites. Results: An interquartile range (IQR, 47.58 μg/m3) increase in 2 hours' ozone exposure was significantly associated with increments of 1.77mmHg in systolic BP and 1.69 mmHg in diastolic BP. Simultaneously,there were increases of 5.20% in ACE and 0.48% in ET-1. DNA methylation of the two cytokines decreased following ozone exposure. An IQR increase in ozone concentrations (0-8 h) was significantly associated with 0.20 % decrease in locus-average ACE methylation. The inverse association between ozone exposure and ET-1 methylation only occurred in one locus. Metabolomic analysis showed meaningful changes following ozone exposure in serum lipid metabolites in relation to vascular endothelial dysfunction. Conclusions: Our findings highlighted a potential mechanistic pathway linking acute ozone exposure to increased blood pressure and vascular endothelial dysfunction.