Zhu Yutong, Xu Hongbing, Wang Tong, Xie Yunfei, Liu Lingyan, He Xinghou, Liu Changjie, Zhao Qian, Song Xiaoming, Zheng Lemin, Huang Wei
Department of Occupational and Environmental Health, Peking University School of Public Health, and Peking University Institute of Environmental Medicine, Beijing, 100191, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China.
Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, Peking University School of Basic Medical Sciences, Beijing, 100191, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China.
Environ Pollut. 2023 Oct 15;335:122301. doi: 10.1016/j.envpol.2023.122301. Epub 2023 Aug 2.
Air pollution has been associated with the development of atherosclerosis; however, the pathophysiological mechanisms underlying pro-atherosclerotic effects of air pollution exposure remain unclear. We conducted a prospective panel study in Beijing and recruited 152 participants with four monthly visits from September 2019 to January 2020. Linear mixed-effect models were applied to estimate the associations linking short-term air pollution exposure to biomarkers relevant to ceramide metabolism, pro-inflammation (neutrophil extracellular traps formation and systemic inflammation) and pro-atherosclerotic responses (endothelial stimulation, plaque instability, coagulation activation, and elevated blood pressure). We further explored whether ceramides and inflammatory indicators could mediate the alterations in the profiles of pro-atherosclerotic responses. We found that significant increases in levels of circulating ceramides of 9.7% (95% CIs: 0.7, 19.5) to 96.9% (95% CIs: 23.1, 214.9) were associated with interquartile range increases in moving averages of ambient air pollutant metrics, including fine particulate matter (PM), black carbon, particles in size fractions of 100-560 nm, nitrogen dioxide, carbon monoxide and sulfur dioxide at prior up to 7 days. Higher air pollution levels were also associated with activated neutrophils (increases in citrullinated histone H3, neutrophil elastase, double-stranded DNA, and myeloperoxidase) and exacerbation of pro-atherosclerotic responses (e.g., increases in vascular endothelial growth factor, lipoprotein-associated phospholipase A2, matrix metalloproteinase-8, P-selectin, and blood pressure). Mediation analyses further showed that dysregulated ceramide metabolism and potentiated inflammation could mediate PM-associated pro-atherosclerotic responses. Our findings extend the understanding on potential mechanisms of air pollution-associated atherosclerosis, and suggest the significance of reducing air pollution as priority in urban environments.
空气污染与动脉粥样硬化的发展有关；然而，接触空气污染产生促动脉粥样硬化作用的病理生理机制仍不清楚。我们在北京进行了一项前瞻性队列研究，招募了152名参与者，从2019年9月至2020年1月每月进行一次随访。应用线性混合效应模型来估计短期空气污染暴露与与神经酰胺代谢、促炎（中性粒细胞胞外陷阱形成和全身炎症）和促动脉粥样硬化反应（内皮刺激、斑块不稳定、凝血激活和血压升高）相关的生物标志物之间的关联。我们进一步探讨了神经酰胺和炎症指标是否可以介导促动脉粥样硬化反应谱的改变。我们发现，循环神经酰胺水平显著升高9.7%（95%置信区间：0.7，19.5）至96.9%（95%置信区间：23.1，214.9）与前7天环境空气污染物指标移动平均值的四分位数间距增加有关，这些指标包括细颗粒物（PM）、黑碳、粒径在100 - 560纳米的颗粒物、二氧化氮、一氧化碳和二氧化硫。更高的空气污染水平还与活化的中性粒细胞（瓜氨酸化组蛋白H3、中性粒细胞弹性蛋白酶、双链DNA和髓过氧化物酶增加）以及促动脉粥样硬化反应的加剧（如血管内皮生长因子、脂蛋白相关磷脂酶A2、基质金属蛋白酶 - 8、P - 选择素和血压升高）有关。中介分析进一步表明，神经酰胺代谢失调和炎症增强可介导与PM相关的促动脉粥样硬化反应。我们的研究结果扩展了对空气污染相关动脉粥样硬化潜在机制的理解，并表明在城市环境中优先减少空气污染的重要性。
