Abstract：
Exposure to fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) is known to be associated with the polarization of pro-inflammatory macrophages and the development of various cardiovascular diseases. The pro-inflammatory polarization of resident cardiac macrophages (cMacs) enhances the cleavage of membrane-bound myeloid-epithelial-reproductive receptor tyrosine kinase (MerTK) and promotes the formation of soluble MerTK (solMER). This process influences the involvement of cMacs in cardiac repair, thus leading to an imbalance in cardiac homeostasis, myocardial injury, and reduced cardiac function. However, the relative impacts of PM2.5 and PAHs on human cMacs have yet to be elucidated. In this study, we aimed to investigate the effects of PM2.5 and PAH exposure on solMER in terms of myocardial injury and left ventricular (LV) systolic function in healthy children. A total of 258 children (aged three to six years) were recruited from Guiyu (an area exposed to e-waste) and Haojiang (a reference area). Mean daily PM2.5 concentration data were collected to calculate the individual chronic daily intake (CDI) of PM2.5. We determined concentrations of solMER and creatine kinase MB (CKMB) in plasma, and hydroxylated PAHs (OH-PAHs) in urine. LV systolic function was evaluated by stroke volume (SV). Higher CDI values and OH-PAH concentrations were detected in the exposed group. Plasma solMER and CKMB were higher in the exposed group and were associated with a reduced SV. Elevated CDI and 1-hydroxynaphthalene (1-OHNa) were associated with a higher solMER. Furthermore, increased solMER concentrations were associated with a lower SV and higher CKMB. CDI and 1-OHNa were positively associated with CKMB and mediated by solMER. In conclusion, exposure to PM2.5 and PAHs may lead to the pro-inflammatory polarization of cMacs and increase the risk of myocardial injury and systolic function impairment in children. Furthermore, the pro-inflammatory polarization of cMacs may mediate cardiotoxicity caused by PM2.5 and PAHs.
摘要：
已知暴露于细颗粒物（PM2.5）和多环芳烃（PAHs）与促炎巨噬细胞的极化和各种心血管疾病的发展有关。常驻心脏巨噬细胞（cMacs）的促炎极化增强了膜结合的骨髓上皮生殖受体酪氨酸激酶（MerTK）的裂解，并促进了可溶性MerTK（solMER）的形成。这个过程影响cMac参与心脏修复，从而导致心脏稳态失衡，心肌损伤，心脏功能下降.然而,PM2.5和PAHs对人类cMac的相对影响尚未阐明。在这项研究中,我们旨在研究PM2.5和PAH暴露对健康儿童solMER心肌损伤和左心室收缩功能的影响。共有258名儿童(3至6岁)从贵屿(电子垃圾暴露区)和郝江(参考区)招募。收集平均每日PM2.5浓度数据以计算PM2.5的个体慢性每日摄入量（CDI）。我们测定了血浆中solMER和肌酸激酶MB（CKMB）的浓度，和尿中的羟基化PAHs(OH-PAHs)。通过每搏输出量（SV）评估左心室收缩功能。在暴露组中检测到更高的CDI值和OH-PAH浓度。暴露组的血浆solMER和CKMB较高，并与SV降低有关。CDI和1-羟基萘（1-OHNa）升高与较高的solMER相关。此外，增加的solMER浓度与较低的SV和较高的CKMB相关。CDI和1-OHNa与CKMB呈正相关，并由solMER介导。总之,暴露于PM2.5和PAHs可能导致cMacs的促炎极化，并增加儿童心肌损伤和收缩功能损害的风险。此外，cMacs的促炎极化可能介导PM2.5和PAHs引起的心脏毒性。
