Neutrophil extracellular traps mediated by platelet microvesicles promote thrombosis and brain injury in acute ischemic stroke

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2024年1月17日

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Xin Gao,
Xinyi Zhao,
Jiacheng Li,
Chang Liu,
Wenqiang Li,
Junjie Zhao,
Zhixi Li,
Nan Wang,
Fang Wang,
Jiawei Dong,
Xiuwei Yan,
Jiheng Zhang,
Xueyan Hu,
Jiaqi Jin,
Ge Mang,
Ruishuang Ma,
Shaoshan Hu

摘要

Aims

Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role of NETs formation in the AIS process.

Methods

As well as 45 healthy subjects, 45 patients with AIS had ELISA tests performed to detect NET markers. Expression of high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) was analyzed by flow cytometry in healthy subjects and AIS patients’ blood samples. We established middle cerebral artery occlusion (MCAO) mice model to elucidate the interaction between PMPs and NETs.

Results

A significant elevation in NET markers was found in patient plasma in AIS patients, and neutrophils generated more NETs from patients’ neutrophils. HMGB1 expression was upregulated on PMVs from AIS patients and induced NET formation. NETs enhanced Procoagulant activity (PCA) through tissue factor and via platelet activation. Targeting lactadherin in genetical and in pharmacology could regulate the formation of NETs in MCAO model.

Conclusions

NETs mediated by PMVs derived HMGB1 exacerbate thrombosis and brain injury in AIS.

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