Shear-Induced Extensional Response Behaviors of Tethered von Willebrand Factor

Wang, Yi; Morabito, Michael; Zhang, Xiao Hui; Webb, Edmund B.; Öztekin, Alparslan; Cheng, Xuanhong

doi:10.1016/j.bpj.2019.04.025

Cited by 20 publications

(28 citation statements)

References 70 publications

(125 reference statements)

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“… 134 NPSS can change VWF multimers from a globular shape to an elongated rope-like structure. 135 Structural changes of VWF molecule induced by NPSS expose the A2 domain 136 , 137 and promote proteolytic cleavage by ADAMTS-13 and multimeric binding to platelets GP1ba through A1 domain. 138 The VWF-platelet binding also increases proteolytic cleavage by ADAMTS-13.…”

Section: Shear-induced Acquired Von Willebrand Syndrome (Avws)mentioning

confidence: 99%

Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation

Wang

Griffith

2021

Clin Appl Thromb Hemost

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Mechanically assisted circulation (MAC) sustains the blood circulation in the body of a patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) or on ventricular assistance with a ventricular assist device (VAD) or on extracorporeal membrane oxygenation (ECMO) with a pump-oxygenator system. While MAC provides short-term (days to weeks) support and long-term (months to years) for the heart and/or lungs, the blood is inevitably exposed to non-physiological shear stress (NPSS) due to mechanical pumping action and in contact with artificial surfaces. NPSS is well known to cause blood damage and functional alterations of blood cells. In this review, we discussed shear-induced platelet adhesion, platelet aggregation, platelet receptor shedding, and platelet apoptosis, shear-induced acquired von Willebrand syndrome (AVWS), shear-induced hemolysis and microparticle formation during MAC. These alterations are associated with perioperative bleeding and thrombotic events, morbidity and mortality, and quality of life in MCS patients. Understanding the mechanism of shear-induce hemostatic disorders will help us develop low-shear-stress devices and select more effective treatments for better clinical outcomes.

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Section: Shear-induced Acquired Von Willebrand Syndrome (Avws)mentioning

confidence: 99%

Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation

Wang

Griffith

2021

Clin Appl Thromb Hemost

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“…The length of VWF multimers significantly affects their responses to shear. A lower threshold of shear rate is required to extend long VWF multimers ( 52 ). A recent research suggested that tension, but not shear stress, regulates the affinity of VWF for platelet glycoprotein Ibα (GPIbα) ( 53 ).…”

Section: The Von Willebrand Factor and Adamts13mentioning

confidence: 99%

Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13

Yang

Long

et al. 2020

Front. Immunol.

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Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.

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“…The details of the microfluidic device design and fabrication can be found in our previous work with slight modification. 24 In this study, PDMS precursor and curing agent (Dow Corning, MI, USA) were mixed at a 5:1 weight ratio to achieve stiffer channels that resist deformation under the hydrodynamic pressure. The mixture was incubated at 60°C for 4 h to cure fully.…”

Section: Microfluidic Device and Vwf Immobilizationmentioning

confidence: 99%

Effect of pulsatility on shear‐induced extensional behavior of Von Willebrand factor

et al. 2021

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Background: Patients with continuous flow ventricular assist devices (CF-VADs) are at high risk for non-surgical bleeding, speculated to associate with the loss of pulsatility following CF-VAD placement. It has been hypothesized that continuous shear stress causes elongation and increased enzymatic degradation of von Willebrand Factor (vWF), a key player in thrombus formation at sites of vascular damage. However, the role of loss of pulsatility on the unravelling behavior of vWF has not been widely explored.Methods: vWF molecules were immobilized on the surface of microfluidic devices and subjected to various pulsatile flow profiles, including continuous flow and pulsatile flow of different magnitudes, dQ/dt (i.e., first derivative of flow rate) of pulsatility and pulse frequencies to mimic in vivo shear flow environments with and without CF-VAD support. VWF elongation was observed using total internal reflection fluorescence (TIRF) microscopy. Besides, the vWF level is measured from the patients' blood sample before and after CF-VAD implantation from a clinical perspective. To our knowledge, this work is the first in providing direct, visual observation of single vWF molecule extension under controlled-pulsatile shear flow. Results: Unravelling of vWF (total sample size n ~ 200 molecules) is significantly reduced under pulsatile flow (p < 0.01) compared to continuous flow. An increase in the magnitude of pulsatility further reduces unravelling lengths, while lower frequency of pulsatility (20 vs. 60 pulses per min) does not have a major effect on the maximum or minimum unravelling lengths. Evaluation of CF-VAD patient blood samples (n = 13) demonstrates that vWF levels decreased by ~40% following CF-VAD placement (p < 0.01), which correlates to single-molecule observations from a clinical point of view. Conclusions: Pulsatile flow reduces unfolding of vWF compared to continuous flow and a lower pulse frequency of 20 pulses/minute yielded comparable vWF unfolding to 60 pulses/minute. These findings could shed light on non-surgical bleeding associated with the loss of pulsatility following CF-VAD placement.

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Shear-Induced Extensional Response Behaviors of Tethered von Willebrand Factor

Cited by 20 publications

References 70 publications

Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation

Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation

Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13

Effect of pulsatility on shear‐induced extensional behavior of Von Willebrand factor

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