Abstract
BackgroundThrombotic diseases are a group of prevalent and life-threatening diseases. Selective inhibition of pathological thrombosis holds the key to treat variety of thrombotic diseases. The pathological thrombosis can be induced by either tissue necrosis and deregulated inflammation. HMGB1, as an important proinflammatory cytokine and a late mediator, also involves on thrombosis disease. However, the underlying mechanisms are not fully understood.MethodsImmunofluorescence, ELISA assay, Platelet Aggregation, Thromboelastogram (TEG) analyzes. Flow cytometric analysis and Western blot analysis were used to investigated the role of HMGB1 in platelet aggregation and obtained following observations.ResultsBy doing so, we obtained the following observations: i) Highly purified HMGB1 recombinant protein induces platelet aggregation and secretion in a dose-dependent manner in the presence of serum. ii) Low concentration of extracellular HMGB1 could synergistically promote subthreshold concentration of collagen or thrombin induced platelet aggregation. iii) Extracellular HMGB1 promoted platelet aggregation in a platelet-expressed GPIIb/IIIa-dependent manner. iv) We proposed that extracellular HMGB1 seems to promote the phosphorylation of GPIIb/IIIa and subsequent platelet aggregation via TLR4/NF-κB and cGMP pathway.ConclusionsIn this study, we provide evidence for the hypothesis that HMGB1 interact with platelet might play an important role in the haemostasis and thrombotic diseases. Our research might be provide an interesting avenue for the treatment of thrombotic diseases in the future.
Highlights
GPIIb/IIIa-dependent manner. iv) We proposed that extracellular HMGB1 seems to promote the phosphorylation of
In this study, we provide evidence for the hypothesis that HMGB1 interact with platelet might play an important role in the haemostasis and thrombotic diseases
E endothelial activation [1], inflammation not Ronly leads to activation of coagulation, and vice versa coagulation considerably affects inflammatory activity and even augments inflammation, at present, the commonly accepted notion that inflammation and hemastasis are coupled by common activation pathway and feedback regulation system [2, 3], generally speaking, inflammation including sterile and infectionassociated inflammation states, but the common features of the two in the process of inflammation are accompanied by cells necrotic and and immune cell activation [3]
Summary
We obtained the following observations: i) Highly purified HMGB1 recombinant protein induces platelet aggregation and secretion in a dose-dependent manner in the presence of serum. ii) Low concentration of extracellular HMGB1 could synergistically promote subthreshold concentration of collagen or. We obtained the following observations: i) Highly purified HMGB1 recombinant protein induces platelet aggregation and secretion in a dose-dependent manner in the presence of serum. Ii) Low concentration of extracellular HMGB1 could synergistically promote subthreshold concentration of collagen or. Iii) Extracellular HMGB1 promoted platelet aggregation in a platelet-expressed. Iv) We proposed that extracellular HMGB1 seems to promote the phosphorylation of. E GPIIb/IIIa and subsequent platelet aggregation via TLR4/NF-κB and cGMP pathway
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