Low-level ambient ozone exposure associated with neutrophil extracellular traps and pro-atherothrombotic biomarkers in healthy adults

Hongbing Xu; Xinghou He; Bin Zhang; Mengyao Li; Yutong Zhu; Tong Wang; Shengcong Liu; Mushui Shu; Ding Ding; Yu Wang; Qian Zhao; Jianping Li; Xiaoming Song; Wei Huang

doi:10.1016/j.atherosclerosis.2024.117509

Low-level ambient ozone exposure associated with neutrophil extracellular traps and pro-atherothrombotic biomarkers in healthy adults

Atherosclerosis. 2024 Mar 7:117509. doi: 10.1016/j.atherosclerosis.2024.117509. Online ahead of print.

Authors

Hongbing Xu¹, Xinghou He¹, Bin Zhang¹, Mengyao Li¹, Yutong Zhu¹, Tong Wang¹, Shengcong Liu², Mushui Shu³, Ding Ding³, Yu Wang³, Qian Zhao¹, Jianping Li², Xiaoming Song⁴, Wei Huang⁵

Affiliations

¹ Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, and Peking University Institute of Environmental Medicine, Beijing, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
² Division of Cardiology, Peking University First Hospital, Beijing, China.
³ Institute of Urban Safety and Environmental Science, Beijing Academy of Science and Technology, Beijing, China.
⁴ Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, and Peking University Institute of Environmental Medicine, Beijing, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. Electronic address: xiaomingsong@bjmu.edu.cn.
⁵ Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, and Peking University Institute of Environmental Medicine, Beijing, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China. Electronic address: whuang@bjmu.edu.cn.

PMID: 38523002
DOI: 10.1016/j.atherosclerosis.2024.117509

Abstract

Background and aims: Uncertainty of the causality determinations for ambient ozone (O₃) on cardiovascular events is heightened by the limited understanding of the mechanisms involved in humans. We aimed to examine the pro-atherothrombotic impacts of O₃ exposure and to explore the potential mediating roles of dysfunctional neutrophils, focusing on neutrophil extracellular traps (NETs).

Methods: A longitudinal panel study of 152 healthy adults was conducted in the cool to cold months with relatively low levels of O₃ between September 2019 and January 2020 in Beijing, China. Four repeated measurements of indicators reflecting atherothrombotic balance and NETs were performed for each participant.

Results: Daily average exposure levels of ambient O₃ were 16.6 μg/m³ throughout the study period. Per interquartile range increase in average concentrations of O₃ exposure at prior up to 7 days, we observed elevations of 200.1-276.3% in D-dimer, 27.2-36.8% in thrombin-antithrombin complex, 10.8-60.3% in plasminogen activator inhibitor 1, 13.9-21.8% in soluble P-selectin, 16.5-45.1% in matrix metalloproteinase-8, and 2.4-12.4% in lipoprotein-associated phospholipase A2. These pro-atherothrombotic changes were accompanied by endothelial activation, lung injury, and immune inflammation. O₃ exposure was also positively associated with circulating NETs indicators, including citrullinated histone H3, neutrophil elastase, myeloperoxidase, and double-stranded DNA. Mediation analyses indicated that NETs could mediate O₃-associated pro-atherothrombotic responses. The observational associations remained significant and robust after controlling for other pollutants, and were generally greater in participants with low levels of physical activity.

Conclusions: Ambient O₃ exposure was associated with significant increases in NETs and pro-atherothrombotic potential, even at exposure levels well below current air quality guidelines of the World Health Organization.

Keywords: Air pollution; Atherothrombotic balance; Neutrophil extracellular traps; Ozone.