Key result
HMGB1 induced tissue factor expression in vascular endothelial cells via cell surface receptors (TLR4, TLR2, and RAGE) and activation of transcription factors NF-kappaB and Egr-1.
HMGB1 induces tissue factor expression in vascular endothelial cells via TLR4, TLR2, and RAGE receptors and activation of NF-κB and Egr-1, suggesting a potential role in the pathogenesis of atherothrombosis.
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-kappaB (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-kappaB and Egr-1).
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Wang et al. (2009) studied Atherothrombosis. High-mobility group box 1 protein (HMGB1) was evaluated on Tissue factor (TF) expression in vascular endothelial cells. HMGB1 induced tissue factor expression in vascular endothelial cells via cell surface receptors (TLR4, TLR2, and RAGE) and activation of transcription factors NF-kappaB and Egr-1.
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