Lead-induced actin polymerization aggravates neutrophil extracellular trap formation and contributes to vascular
Qiying Nong1, Yanjun Wu2, Suhui Liu3
1Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
Insights
Lead exposure damages cardiovascular health by affecting neutrophils and their role in forming neutrophil extracellular traps (NETs). Inhibiting actin polymerization reduces NETs, mitigating lead-induced vascular inflammation and high blood pressure.
Area of Science:
- Toxicology
- Cardiovascular Biology
- Immunology
Background:
- Lead (Pb) exposure is a known cardiovascular disease risk factor.
- Neutrophil involvement in Pb-induced cardiovascular injury is established, but mechanisms are unclear.
- Understanding Pb's targets in neutrophils is crucial for elucidating cardiovascular damage pathways.
Purpose of the Study:
- To identify Pb binding targets within neutrophils.
- To investigate the role of these targets in neutrophil extracellular trap (NET) formation.
- To determine the impact of Pb-induced NET formation on vascular inflammation and cardiovascular injury in vivo.
Main Methods:
- Investigated Pb binding targets in neutrophils.
- Assessed the effect of Pb on actin polymerization and NET formation markers (myeloperoxidase, neutrophil elastase, citrullinated histone H3).
- Utilized a mouse model to study Pb exposure effects on blood pressure, vascular inflammation, and aortic blood flow, correlating these with NET levels.
Main Results:
- Pb was found to bind to β-actin in neutrophils, influencing NET formation.
- Inhibition of actin polymerization significantly reduced NET release.
- Pb exposure exacerbated hypertension and vascular inflammation in mice, linked to increased NET formation.
- Inhibition of actin polymerization ameliorated Pb-induced cardiovascular damage by reducing NETs.
Conclusions:
- Pb binds to neutrophil β-actin, promoting NET formation and contributing to cardiovascular injury.
- Targeting actin polymerization presents a potential therapeutic strategy to mitigate Pb-induced cardiovascular damage.
- This study elucidates a novel mechanism linking lead exposure, neutrophil function, and cardiovascular disease progression.
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.
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