2. Academic Validation
  3. Neutrophil extracellular traps promote thrombogenicity in cerebral venous sinus thrombosis

Neutrophil extracellular traps promote thrombogenicity in cerebral venous sinus thrombosis

  • Cell Biosci. 2022 Jul 22;12(1):114. doi: 10.1186/s13578-022-00845-z.
Jiaqi Jin  # 1 2,  Shan Qiao  # 3,  Jie Liu  # 1,  Wenqiang Li 4,  Fang Wang 1 2,  Xin Gao 1 2,  Jiawei Tian 1 2,  Nan Wang 1 2,  Jiheng Zhang 1 2,  Jiawei Dong 1 2,  Haiyun Li 5,  Jianjun Wang 6,  Shaoshan Hu 7 8,  Peng Zhou 9
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • 2 Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
  • 3 Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
  • 4 Department of Vascular Surgery, Jinshan Hospital of Fudan University, Shanghai, China.
  • 5 Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 6 Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. 1499@sdhospital.com.cn.
  • 7 Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. shaoshanhu421@163.com.
  • 8 Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. shaoshanhu421@163.com.
  • 9 Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. zhoupeng2933@126.com.
  • # Contributed equally.
PMID: 35869501 DOI: 10.1186/s13578-022-00845-z
Abstract

Background: Neutrophil extracellular traps (NETs) contribute to the creation of a coagulation state in various diseases. Currently, it is not clear whether NETs are present in the thrombi and plasma of patients with cerebral venous sinus thrombosis (CVST). This study aimed to investigate the presence of NETs in thrombi and blood samples from CVST patients and the procoagulant activity (PCA) of NETs during the progression of CVST.

Results: Thrombi obtained from CVST patients undergoing thrombectomy were examined by immunochemistry using neutrophil Elastase (NE), CD66b and citrullinated histone H3(citH3). The presence of NET markers in samples from 37 CVST patients and 32 healthy people was evaluated by ELISA. NET-producing neutrophils and neutrophil-platelet (PLT) aggregates were examined in samples obtained from CVST patients and healthy people by flow cytometry. The TAT complex in plasma sample from each group was detected by ELISA to evaluate the procoagulant activity of NETs in CVST patients. Neutrophils from healthy subjects were treated with PLT-rich plasma in the presence of anti-PF4 Antibodies or an Autophagy Inhibitor and analyzed by flow cytometry and confocal microscopy. After treatment with NETs, the expression of von Willebrand factor (VWF), tissue factor (TF) and CD31 in human brain microvascular endothelial cells (HBMECs) was measured by confocal microscopy and western blotting. Our results showed that NETs were abundant in the plasma and thrombi from CVST patients. Platelet Factor 4 (PF4) from CVST PLTs induced NET generation through Autophagy. NETs could induce PCA by modulating TF and phosphatidylserine (PS) in CVST. NETs also disrupted the endothelial barrier and transformed ECs into a procoagulant phenotype to exacerbate thrombogenicity.

Conclusions: NET generation was mediated by PF4 from PLTs through Autophagy and contribute to thrombosis in CVST patients.

Keywords

Cerebral venous sinus thrombosis; Coagulation; Endothelial dysfunction; Neutrophil extracellular traps; Platelet factor 4.

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