Author:
Gao Xin,Zhao Xinyi,Li Jiacheng,Liu Chang,Li Wenqiang,Zhao Junjie,Li Zhixi,Wang Nan,Wang Fang,Dong Jiawei,Yan Xiuwei,Zhang Jiheng,Hu Xueyan,Jin Jiaqi,Mang Ge,Ma Ruishuang,Hu Shaoshan
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology,Biochemistry