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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Fluids |
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| Online Access: | https://www.mdpi.com/2311-5521/6/2/67 |
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| author | Alireza Sharifi David Bark |
| author_facet | Alireza Sharifi David Bark |
| author_sort | Alireza Sharifi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:54:08Z |
| format | Article |
| id | doaj.art-4179525cc0df4dec80b64f95e8f9e762 |
| institution | Directory Open Access Journal |
| issn | 2311-5521 |
| language | English |
| last_indexed | 2024-03-09T05:54:08Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Fluids |
| spelling | doaj.art-4179525cc0df4dec80b64f95e8f9e7622023-12-03T12:14:36ZengMDPI AGFluids2311-55212021-02-01626710.3390/fluids6020067Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood FlowAlireza Sharifi0David Bark1Department of Mechanical Engineering, Colorado State University, Fort Collins, CO 80523, USADepartment of Pediatrics, Washington University in Saint Louis, Saint Louis, MO 63130, USAVon 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.https://www.mdpi.com/2311-5521/6/2/67von Willebrand factorVWFcleavageshearelongational flowturbulence |
| spellingShingle | Alireza Sharifi David Bark Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow Fluids von Willebrand factor VWF cleavage shear elongational flow turbulence |
| title | Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow |
| title_full | Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow |
| title_fullStr | Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow |
| title_full_unstemmed | Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow |
| title_short | Mechanical Forces Impacting Cleavage of Von Willebrand Factor in Laminar and Turbulent Blood Flow |
| title_sort | mechanical forces impacting cleavage of von willebrand factor in laminar and turbulent blood flow |
| topic | von Willebrand factor VWF cleavage shear elongational flow turbulence |
| url | https://www.mdpi.com/2311-5521/6/2/67 |
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