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Thromb Haemost 2009; 102(02): 352-359
DOI: 10.1160/TH08-11-0759
Endothelium and Vascular Development
Schattauer GmbH

High-mobility group box 1 protein induces tissue factor expression in vascular endothelial cells via activation of NF-κB and Egr-1

Ben Lv
1   Department of Hemotology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China
4   Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China
,
Haichao Wang
2   Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine and Feinstein Institute for Medical Research, Manhasset, New York, USA
,
Yiting Tang
3   Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China
4   Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China
,
Zhang Fan
1   Department of Hemotology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China
,
Xianzhong Xiao
4   Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China
,
Fangping Chen
1   Department of Hemotology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China
› Author Affiliations
Further Information

Publication History

Received: 24 August 2008

Accepted after major revision: 21 May 2009

Publication Date:
22 November 2017 (online)

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Summary

High-mobility group box 1 protein (HMGB1), an abundant nuclear protein, was recently established as a proinflammatory mediator of experimental sepsis.Although extracellular HMGB1 has been found in atherosclerotic plaques, its potential role in the pathogenesis of atherothrombosis remains elusive. In the present study, we determined whether HMGB1 induces tissue factor (TF) expression in vascular endothelial cells (ECs) and macrophages. Our data showed that HMGB1 stimulated ECs to express TF (but not TF pathway inhibitor) mRNA and protein in a concentration and time-dependent manner. Blockade of cell surface receptors (including TLR4, TLR2, and RAGE) with specific neutralising antibodies partially reduced HMGB1-induced TF expression. Moreover, HMGB1 increased expression of Egr-1 and nuclear translocation of NF-κB (c-Rel/p65) in ECs. Taken together, our data suggest that HMGB1 induces TF expression in vascular endothelial cells via cell surface receptors (TLR4, TLR2, and RAGE), and through activation of transcription factors (NF-κB and Egr-1).

Keywords

Tissue factor - HMGB1 - thrombosis - atherosclerosis
 

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