Neutrophil Extracellular Traps Mediated by Platelet Microvesicles Promote Thrombosis and Brain Injury in Acute Ischemic Stroke

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2024 Jan 17

PMID 38233928

Authors

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

Affiliations

Soon will be listed here.

Abstract

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. Video Abstract.

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