Nong Qiying, Wu Yanjun, Liu Suhui, Tang Yinyin, Wu Jiayun, Huang Hongmei, Hong Jiaying, Qin Yiru, Xu Ruimei, Zhao Wenxia, Chen Baowei, Huang Zhenlie, Hu Ligang, Zhao Na, Huang Yongshun
Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; Guangming District Center for Disease Control and Prevention, Shenzhen 518016, China; Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Ecotoxicol Environ Saf. 2025 Jan 15;290:117598. doi: 10.1016/j.ecoenv.2024.117598. Epub 2024 Dec 24.
Lead (Pb) exposure is widely acknowledged as a risk factor for cardiovascular diseases. Previous studies have established neutrophil involvement in Pb-induced cardiovascular injuries; however, the underlying mechanisms remain unclear. To address this knowledge gap, the binding targets of Pb in neutrophils and their roles in regulating neutrophil extracellular trap (NET) formation were investigated. Furthermore, their impact on Pb-induced vascular inflammation and other cardiovascular injuries was studied in mice. Our findings indicate, for the first time, that Pb binds to β-actin in neutrophils, influencing NET formation. Inhibition of actin polymerization reduces the release of extracellular myeloperoxidase, neutrophil elastase, and citrullinated histone H3, indicating an impediment in NET formation. Furthermore, Pb exposure exacerbates blood pressure and vascular inflammation in vascular tissues, leading to abnormal aortic blood flow in mice. These injuries are potentially associated with NET formation, which is supported by the positive correlation between NETs and vascular inflammation. Importantly, the inhibition of actin polymerization mitigates Pb-induced vascular inflammation and regulates systolic blood pressure by reducing NET formation. Collectively, our findings provide novel insights into the mechanism underlying Pb-induced cardiovascular injury, contributing to the management of the escalating risk associated with Pb-induced cardiovascular damage.
铅（Pb）暴露被广泛认为是心血管疾病的一个风险因素。先前的研究已证实中性粒细胞参与了铅诱导的心血管损伤；然而，其潜在机制仍不清楚。为了填补这一知识空白，我们研究了铅在中性粒细胞中的结合靶点及其在调节中性粒细胞胞外诱捕网（NET）形成中的作用。此外，还在小鼠中研究了它们对铅诱导的血管炎症和其他心血管损伤的影响。我们的研究结果首次表明，铅与中性粒细胞中的β-肌动蛋白结合，影响NET的形成。抑制肌动蛋白聚合可减少细胞外髓过氧化物酶、中性粒细胞弹性蛋白酶和瓜氨酸化组蛋白H3的释放，表明NET形成受到阻碍。此外，铅暴露会加剧血管组织中的血压和血管炎症，导致小鼠主动脉血流异常。这些损伤可能与NET形成有关，NET与血管炎症之间的正相关支持了这一点。重要的是，抑制肌动蛋白聚合可减轻铅诱导的血管炎症，并通过减少NET形成来调节收缩压。总的来说，我们的研究结果为铅诱导心血管损伤的潜在机制提供了新的见解，有助于应对与铅诱导心血管损伤相关的不断上升的风险。
