Biomaterial Database

Platelet factor 4 inhibits ADAMTS13 activity and regulates the multimeric distribution of von Willebrand factor. 2020

Ishac Nazy, and Taylor D Elliott, and Donald M Arnold

Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.

The efficiency of von Willebrand factor (VWF) in thrombus formation is related to its multimeric size, which is controlled by the protease ADAMTS13. However, it is not clear what regulates ADAMTS13 activity. In this study, we investigated whether PF4 could bind to VWF and inhibit ADAMTS13 activity. We found that PF4 binds to VWF and protects against ADAMTS13 activity. We also found that VWF-PF4 complexes circulate in patients with thrombotic thrombocytopenic purpura (TTP). Our data provides the first evidence that PF4 may have a novel role in regulating VWF multimers during primary haemostasis and thrombosis.

UI	MeSH Term	Description	Entries
D010978	Platelet Factor 4	A CXC chemokine that is found in the alpha granules of PLATELETS. The protein has a molecular size of 7800 kDa and can occur as a monomer, a dimer or a tetramer depending upon its concentration in solution. Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C.	Antiheparin Factor,CXCL4 Chemokine,Chemokine CXCL4,Heparin Neutralizing Protein,PF4 (Platelet Factor 4),gamma-Thromboglobulin,CXCL4, Chemokine,Chemokine, CXCL4,gamma Thromboglobulin
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D006487	Hemostasis	The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.	Hemostases
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071120	ADAMTS13 Protein	An ADAMTS protease that contains eight thrombospondin (TS) motifs. It cleaves VON WILLEBRAND FACTOR to control vWF-mediated THROMBOSIS. Mutations in the ADAMTS13 gene have been identified in familial cases of PURPURA, THROMBOTIC THROMBOCYTOPENIC and defects in ADAMTS13 activity are associated with MYOCARDIAL INFARCTION; BRAIN ISCHEMIA; PRE-ECLAMPSIA; and MALARIA.	A Disintegrin and Metalloproteinase with Thrombospondin Motifs 13 Protein,ADAMTS-13 Protein,ADAMTS13 Protease,vWF-Cleaving Protease,von Willebrand Factor-Cleaving Protease,ADAMTS 13 Protein,vWF Cleaving Protease,von Willebrand Factor Cleaving Protease
D000072417	Protein Domains	Discrete protein structural units that may fold independently of the rest of the protein and have their own functions.	Peptide Domain,Protein Domain,Domain, Peptide,Domain, Protein,Domains, Peptide,Domains, Protein,Peptide Domains
D013927	Thrombosis	Formation and development of a thrombus or blood clot in BLOOD VESSELS.	Atherothrombosis,Thrombus,Blood Clot,Blood Clots,Thromboses
D014841	von Willebrand Factor	A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor.	Factor VIII-Related Antigen,Factor VIIIR-Ag,Factor VIIIR-RCo,Plasma Factor VIII Complex,Ristocetin Cofactor,Ristocetin-Willebrand Factor,von Willebrand Protein,Factor VIII Related Antigen,Factor VIIIR Ag,Factor VIIIR RCo,Ristocetin Willebrand Factor
D016553	Purpura, Thrombocytopenic, Idiopathic	Thrombocytopenia occurring in the absence of toxic exposure or a disease associated with decreased platelets. It is mediated by immune mechanisms, in most cases IMMUNOGLOBULIN G autoantibodies which attach to platelets and subsequently undergo destruction by macrophages. The disease is seen in acute (affecting children) and chronic (adult) forms.	Autoimmune Thrombocytopenic Purpura,Idiopathic Thrombocytopenic Purpura,Purpura, Thrombocytopenic, Autoimmune,Werlhof's Disease,Autoimmune Thrombocytopenia,Immune Thrombocytopenia,Immune Thrombocytopenic Purpura,Thrombocytopenic Purpura, Autoimmune,Werlhof Disease,Autoimmune Thrombocytopenias,Autoimmune Thrombocytopenic Purpuras,Disease, Werlhof,Disease, Werlhof's,Idiopathic Thrombocytopenic Purpuras,Immune Thrombocytopenias,Immune Thrombocytopenic Purpuras,Purpura, Autoimmune Thrombocytopenic,Purpura, Idiopathic Thrombocytopenic,Purpura, Immune Thrombocytopenic,Purpuras, Autoimmune Thrombocytopenic,Purpuras, Idiopathic Thrombocytopenic,Purpuras, Immune Thrombocytopenic,Thrombocytopenia, Autoimmune,Thrombocytopenia, Immune,Thrombocytopenias, Autoimmune,Thrombocytopenias, Immune,Thrombocytopenic Purpura, Idiopathic,Thrombocytopenic Purpura, Immune,Thrombocytopenic Purpuras, Idiopathic,Thrombocytopenic Purpuras, Immune,Werlhofs Disease
D055503	Protein Multimerization	The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.	Protein Dimerization,Protein Heteromultimerizaton,Protein Multimer Assembly,Protein Trimerization,Assembly, Protein Multimer,Dimerization, Protein,Heteromultimerizaton, Protein,Heteromultimerizatons, Protein,Multimer Assembly, Protein,Multimerization, Protein,Trimerization, Protein