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.
Division of Cardiology, Peking University First Hospital, Beijing, China.
Atherosclerosis. 2024 Aug;395:117509. doi: 10.1016/j.atherosclerosis.2024.117509. Epub 2024 Mar 7.
Uncertainty of the causality determinations for ambient ozone (O) on cardiovascular events is heightened by the limited understanding of the mechanisms involved in humans. We aimed to examine the pro-atherothrombotic impacts of O exposure and to explore the potential mediating roles of dysfunctional neutrophils, focusing on neutrophil extracellular traps (NETs).
A longitudinal panel study of 152 healthy adults was conducted in the cool to cold months with relatively low levels of O between September 2019 and January 2020 in Beijing, China. Four repeated measurements of indicators reflecting atherothrombotic balance and NETs were performed for each participant.
Daily average exposure levels of ambient O were 16.6 μg/m throughout the study period. Per interquartile range increase in average concentrations of O 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. O 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 O-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.
Ambient O 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.
由于人们对涉及人类的机制知之甚少，因此，臭氧（O）对心血管事件的因果关系的不确定性加剧。我们旨在研究 O 暴露对动脉粥样血栓形成的影响，并探索功能失调的中性粒细胞的潜在介导作用，重点是中性粒细胞胞外陷阱（NETs）。
在中国北京的 2019 年 9 月至 2020 年 1 月期间，在相对较低的 O 水平的凉爽至寒冷月份，进行了一项针对 152 名健康成年人的纵向小组研究。为每个参与者进行了 4 次重复测量，以反映动脉粥样血栓形成平衡和 NETs 的指标。
整个研究期间，环境 O 的日平均暴露水平为 16.6μg/m。与之前 7 天的平均 O 暴露浓度相比，每增加一个四分位间距，我们观察到 D-二聚体升高 200.1-276.3%，凝血酶-抗凝血酶复合物升高 27.2-36.8%，纤溶酶原激活物抑制剂 1 升高 10.8-60.3%，可溶性 P-选择素升高 13.9-21.8%，基质金属蛋白酶-8 升高 16.5-45.1%，脂蛋白相关磷脂酶 A2 升高 2.4-12.4%。这些动脉粥样血栓形成的变化伴随着内皮激活、肺损伤和免疫炎症。O 暴露还与循环 NETs 指标呈正相关，包括瓜氨酸化组蛋白 H3、中性粒细胞弹性蛋白酶、髓过氧化物酶和双链 DNA。中介分析表明，NETs 可以介导 O 相关的动脉粥样血栓形成反应。在控制其他污染物后，观察到的关联仍然显著且稳健，并且在体力活动水平较低的参与者中通常更大。
即使在远低于世界卫生组织现行空气质量指南的暴露水平下，环境 O 暴露也与 NETs 和动脉粥样血栓形成潜力的显著增加有关。
