2. Academic Validation
  3. Lead-induced actin polymerization aggravates neutrophil extracellular trap formation and contributes to vascular inflammation

Lead-induced actin polymerization aggravates neutrophil extracellular trap formation and contributes to vascular inflammation

  • Ecotoxicol Environ Saf. 2024 Dec 24:290:117598. doi: 10.1016/j.ecoenv.2024.117598.
Qiying Nong 1,  Yanjun Wu 2,  Suhui Liu 3,  Yinyin Tang 4,  Jiayun Wu 5,  Hongmei Huang 3,  Jiaying Hong 5,  Yiru Qin 1,  Ruimei Xu 6,  Wenxia Zhao 6,  Baowei Chen 7,  Zhenlie Huang 8,  Ligang Hu 9,  Na Zhao 10,  Yongshun Huang 11
Affiliations

Affiliations

  • 1 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
  • 2 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.
  • 3 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
  • 4 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • 5 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China.
  • 6 Material Microanalysis Division, Instrumental Analysis & Research Center, Sun Yat-Sen University, Guangzhou 510275, China.
  • 7 Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
  • 8 Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
  • 9 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Institute of Environment and Health, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310000, China.
  • 10 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China. Electronic address: zhaonabmu@126.com.
  • 11 Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China; Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China; School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China. Electronic address: ysh_huang@126.com.
PMID: 39721424 DOI: 10.1016/j.ecoenv.2024.117598
Abstract

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.

Keywords

Actin polymerization; Cardiovascular injury; Heavy metal; Hypertension; Neutrophil extracellular trap.

Figures
Products