Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow

Von Willebrand factor (VWF) is a large multimeric hemostatic protein. VWF is critical in arresting platelets in regions of high shear stress found in blood circulation. Excessive cleavage of VWF that leads to reduced VWF multimer size in plasma can cause acquired von Willebrand syndrome, which is a...
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Autor*in:	Alireza Sharifi [verfasserIn] David Bark [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	von Willebrand factor VWF cleavage shear elongational flow turbulence

Übergeordnetes Werk:	In: Fluids - MDPI AG, 2016, 6(2021), 2, p 67
Übergeordnetes Werk:	volume:6 ; year:2021 ; number:2, p 67

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/fluids6020067

Katalog-ID:	DOAJ053957563

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520			\|a Von Willebrand factor (VWF) is a large multimeric hemostatic protein. VWF is critical in arresting platelets in regions of high shear stress found in blood circulation. Excessive cleavage of VWF that leads to reduced VWF multimer size in plasma can cause acquired von Willebrand syndrome, which is a bleeding disorder found in some heart valve diseases and in patients receiving mechanical circulatory support. It has been proposed that hemodynamics (blood flow) found in these environments ultimately leads to VWF cleavage. In the context of experiments reported in the literature, scission theory, developed for polymers, is applied here to provide insight into flow that can produce strong extensional forces on VWF that leads to domain unfolding and exposure of a cryptic site for cleavage through a metalloproteinase. Based on theoretical tensile forces, laminar flow only enables VWF cleavage when shear rate is large enough (<2800 s<sup<−1</sup<) or when VWF is exposed to constant shear stress for nonphysiological exposure times (<20 min). Predicted forces increase in turbulence, increasing the chance for VWF cleavage. These findings can be used when designing blood-contacting medical devices by providing hemodynamic limits to these devices that can otherwise lead to acquired von Willebrand syndrome.
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language	English
source	In Fluids 6(2021), 2, p 67 volume:6 year:2021 number:2, p 67
sourceStr	In Fluids 6(2021), 2, p 67 volume:6 year:2021 number:2, p 67
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topic_facet	von Willebrand factor VWF cleavage shear elongational flow turbulence Thermodynamics Descriptive and experimental mechanics
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Predicted forces increase in turbulence, increasing the chance for VWF cleavage. 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callnumber-first	Q - Science
author	Alireza Sharifi
spellingShingle	Alireza Sharifi misc QC310.15-319 misc QC120-168.85 misc von Willebrand factor misc VWF misc cleavage misc shear misc elongational flow misc turbulence misc Thermodynamics misc Descriptive and experimental mechanics Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow
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topic_title	QC310.15-319 QC120-168.85 Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow von Willebrand factor VWF cleavage shear elongational flow turbulence
topic	misc QC310.15-319 misc QC120-168.85 misc von Willebrand factor misc VWF misc cleavage misc shear misc elongational flow misc turbulence misc Thermodynamics misc Descriptive and experimental mechanics
topic_unstemmed	misc QC310.15-319 misc QC120-168.85 misc von Willebrand factor misc VWF misc cleavage misc shear misc elongational flow misc turbulence misc Thermodynamics misc Descriptive and experimental mechanics
topic_browse	misc QC310.15-319 misc QC120-168.85 misc von Willebrand factor misc VWF misc cleavage misc shear misc elongational flow misc turbulence misc Thermodynamics misc Descriptive and experimental mechanics
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title	Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow
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title_full	Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow
author_sort	Alireza Sharifi
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title_sort	mechanical forces impacting cleavage of von willebrand factor in laminar and turbulent blood flow
callnumber	QC310.15-319
title_auth	Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow
abstract	Von Willebrand factor (VWF) is a large multimeric hemostatic protein. VWF is critical in arresting platelets in regions of high shear stress found in blood circulation. Excessive cleavage of VWF that leads to reduced VWF multimer size in plasma can cause acquired von Willebrand syndrome, which is a bleeding disorder found in some heart valve diseases and in patients receiving mechanical circulatory support. It has been proposed that hemodynamics (blood flow) found in these environments ultimately leads to VWF cleavage. In the context of experiments reported in the literature, scission theory, developed for polymers, is applied here to provide insight into flow that can produce strong extensional forces on VWF that leads to domain unfolding and exposure of a cryptic site for cleavage through a metalloproteinase. Based on theoretical tensile forces, laminar flow only enables VWF cleavage when shear rate is large enough (<2800 s<sup<−1</sup<) or when VWF is exposed to constant shear stress for nonphysiological exposure times (<20 min). Predicted forces increase in turbulence, increasing the chance for VWF cleavage. These findings can be used when designing blood-contacting medical devices by providing hemodynamic limits to these devices that can otherwise lead to acquired von Willebrand syndrome.
abstractGer	Von Willebrand factor (VWF) is a large multimeric hemostatic protein. VWF is critical in arresting platelets in regions of high shear stress found in blood circulation. Excessive cleavage of VWF that leads to reduced VWF multimer size in plasma can cause acquired von Willebrand syndrome, which is a bleeding disorder found in some heart valve diseases and in patients receiving mechanical circulatory support. It has been proposed that hemodynamics (blood flow) found in these environments ultimately leads to VWF cleavage. In the context of experiments reported in the literature, scission theory, developed for polymers, is applied here to provide insight into flow that can produce strong extensional forces on VWF that leads to domain unfolding and exposure of a cryptic site for cleavage through a metalloproteinase. Based on theoretical tensile forces, laminar flow only enables VWF cleavage when shear rate is large enough (<2800 s<sup<−1</sup<) or when VWF is exposed to constant shear stress for nonphysiological exposure times (<20 min). Predicted forces increase in turbulence, increasing the chance for VWF cleavage. These findings can be used when designing blood-contacting medical devices by providing hemodynamic limits to these devices that can otherwise lead to acquired von Willebrand syndrome.
abstract_unstemmed	Von Willebrand factor (VWF) is a large multimeric hemostatic protein. VWF is critical in arresting platelets in regions of high shear stress found in blood circulation. Excessive cleavage of VWF that leads to reduced VWF multimer size in plasma can cause acquired von Willebrand syndrome, which is a bleeding disorder found in some heart valve diseases and in patients receiving mechanical circulatory support. It has been proposed that hemodynamics (blood flow) found in these environments ultimately leads to VWF cleavage. In the context of experiments reported in the literature, scission theory, developed for polymers, is applied here to provide insight into flow that can produce strong extensional forces on VWF that leads to domain unfolding and exposure of a cryptic site for cleavage through a metalloproteinase. Based on theoretical tensile forces, laminar flow only enables VWF cleavage when shear rate is large enough (<2800 s<sup<−1</sup<) or when VWF is exposed to constant shear stress for nonphysiological exposure times (<20 min). Predicted forces increase in turbulence, increasing the chance for VWF cleavage. These findings can be used when designing blood-contacting medical devices by providing hemodynamic limits to these devices that can otherwise lead to acquired von Willebrand syndrome.
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container_issue	2, p 67
title_short	Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow
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Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow

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