Abstract
von Willebrand factor (VWF) is a multimeric plasma glycoprotein (GP) involved in platelet adhesion at the site of vascular damage, which acts as a bridge between the injured subendothelium and the platelet receptors. The multimeric structure of VWF allows it to support multiple interactions with platelets and endothelial components under high shear stress. Rapid flow conditions induce a conformational transition of the VWF molecule, thus allowing its functional binding domains to be exposed. A specific VWF-cleaving protease (ADAMTS-13) physiologically down regulates the multimeric size of newly released and circulating VWF in order to prevent unwanted platelet thrombus formation. The occurrence of microvascular platelet aggregation in thrombotic thrombocytopenic purpura, which is caused by an ADAMTS-13 deficiency, well-demonstrates the important role of the protease in regulating the adhesive activity of VWF. Better knowledge of VWF function would contribute to the development of novel anti-thrombotic strategies based on the selective inhibition of the VWF interaction with platelet receptors and endothelial components in areas of the circulation characterised by elevated fluid dynamic forces.
Keywords: ADAMTS-13, haemostasis, platelets, shear stress, thrombosis, von Willebrand disease, von Willebrand factor, on Willebrand factor-cleaving protease
Cardiovascular & Hematological Agents in Medicinal Chemistry
Title: von Willebrand Factor, von Willebrand Factor-Cleaving Protease, and Shear Stress
Volume: 5 Issue: 4
Author(s): P. Perutelli and A. C. Molinari
Affiliation:
Keywords: ADAMTS-13, haemostasis, platelets, shear stress, thrombosis, von Willebrand disease, von Willebrand factor, on Willebrand factor-cleaving protease
Abstract: von Willebrand factor (VWF) is a multimeric plasma glycoprotein (GP) involved in platelet adhesion at the site of vascular damage, which acts as a bridge between the injured subendothelium and the platelet receptors. The multimeric structure of VWF allows it to support multiple interactions with platelets and endothelial components under high shear stress. Rapid flow conditions induce a conformational transition of the VWF molecule, thus allowing its functional binding domains to be exposed. A specific VWF-cleaving protease (ADAMTS-13) physiologically down regulates the multimeric size of newly released and circulating VWF in order to prevent unwanted platelet thrombus formation. The occurrence of microvascular platelet aggregation in thrombotic thrombocytopenic purpura, which is caused by an ADAMTS-13 deficiency, well-demonstrates the important role of the protease in regulating the adhesive activity of VWF. Better knowledge of VWF function would contribute to the development of novel anti-thrombotic strategies based on the selective inhibition of the VWF interaction with platelet receptors and endothelial components in areas of the circulation characterised by elevated fluid dynamic forces.
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Perutelli P. and Molinari C. A., von Willebrand Factor, von Willebrand Factor-Cleaving Protease, and Shear Stress, Cardiovascular & Hematological Agents in Medicinal Chemistry 2007; 5 (4) . https://dx.doi.org/10.2174/187152507782109863
DOI https://dx.doi.org/10.2174/187152507782109863 |
Print ISSN 1871-5257 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6182 |
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