title: HMGB1: a novel protein that induced platelets active and aggregation via Toll-like receptor-4, NF-κB and cGMP dependent mechanisms.
abstract: BACKGROUND
  Thrombotic 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.
  
  
  METHODS
  Immunofluorescence, 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.
  
  
  RESULTS
  By 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.
  
  
  CONCLUSIONS
  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. Our research might be provide an interesting avenue for the treatment of thrombotic diseases in the future.
authors.affiliation: Depatment of Haematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China. yaokkk223@163.com.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, 11030, USA. Helyyl2243@163.com.
authors.forename: Haichao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Hemotology Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China. Ganyyjj33@163.com.
authors.forename: Menmen
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Depatment of Haematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China. zeng223de@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Depatment of Haematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China. hope058@163.com.|Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, 11030, USA. hope058@163.com.
authors.forename: Ben
authors.initials: B
authors.lastname: Lv
authors.affiliation: Depatment of Haematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China. hope058@163.com.|Department of Hemotology Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China. hope058@163.com.
authors.forename: Fangping
authors.initials: F
authors.lastname: Chen
mesh_terms: D000328:Adult; D001778:Blood Coagulation Disorders / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D006152:Cyclic GMP / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D006152:Cyclic GMP