Factor XII Contact Activation
Autor: | Thomas Renné, Stefan Blankenberg, Elena Burillo, Lynn M. Butler, Clément Naudin |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Conformational change Factor XIIa 030204 cardiovascular system & hematology Protein aggregation Bradykinin Hereditary Angioedema Type III 03 medical and health sciences 0302 clinical medicine Thrombin Zymogen medicine Animals Humans Platelet Blood Coagulation Serine protease Factor XII biology Chemistry Hematology Enzyme Activation 030104 developmental biology Coagulation Biochemistry biology.protein Biophysics Cardiology and Cardiovascular Medicine medicine.drug |
Zdroj: | Seminars in Thrombosis and Hemostasis. 43:814-826 |
ISSN: | 1098-9064 0094-6176 |
Popis: | Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation–associated disease states. |
Databáze: | OpenAIRE |
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