scholarly journals Emerging Microfluidic Approaches for Platelet Mechanobiology and Interplay With Circulatory Systems

2021 ◽  
Vol 8 ◽  
Author(s):  
Yingqi Zhang ◽  
Savindi De Zoysa Ramasundara ◽  
Renee Ellen Preketes-tardiani ◽  
Vivian Cheng ◽  
Hongxu Lu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Von Willebrand Factor ◽  
Plasma Proteins ◽  
Circulatory System ◽  
Microfluidic Platforms ◽  
Hemodynamic Forces ◽  
Vessel Walls ◽  
Sense And Respond ◽  
Von Willebrand ◽  
Willebrand Factor

Understanding how platelets can sense and respond to hemodynamic forces in disturbed blood flow and complexed vasculature is crucial to the development of more effective and safer antithrombotic therapeutics. By incorporating diverse structural and functional designs, microfluidic technologies have emerged to mimic microvascular anatomies and hemodynamic microenvironments, which open the floodgates for fascinating platelet mechanobiology investigations. The latest endothelialized microfluidics can even recapitulate the crosstalk between platelets and the circulatory system, including the vessel walls and plasma proteins such as von Willebrand factor. Hereby, we highlight these exciting microfluidic applications to platelet mechanobiology and platelet–circulatory system interplay as implicated in thrombosis. Last but not least, we discuss the need for microfluidic standardization and summarize the commercially available microfluidic platforms for researchers to obtain reproducible and consistent results in the field.

von Willebrand factor deficiency leads to impaired blood flow recovery after ischaemia in mice

2017 ◽  
Vol 117 (07) ◽  
pp. 1412-1419 ◽  
Author(s):  
Margreet R. de Vries ◽  
Erna A. B. Peters ◽  
Paul H. A. Quax ◽  
A. Yaël Nossent
Keyword(s):  
Blood Flow ◽  
Von Willebrand Factor ◽  
Negative Regulator ◽  
Pia Mater ◽  
Artery Ligation ◽  
Factor Deficiency ◽  
Adductor Muscles ◽  
Gastrocnemius Muscles ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryNeovascularisation, i. e. arteriogenesis and angiogenesis, is an inflammatory process. Therefore attraction and extravasation of leukocytes is essential for effective blood flow recovery after ischaemia. Previous studies have shown that von Willebrand factor (VWF) is a negative regulator of angiogenesis. However, it has also been shown that VWF facilitates leukocyte attraction and extravasation. We aimed to investigate the role of VWF in arteriogenesis and angiogenesis during post-ischaemic neovascularisation. Wild-type (WT) and VWF deficient (VWF-/-) C57BL/6 mice were subjected to hindlimb ischaemia via double ligation of the left femoral artery, and blood flow recovery was followed over time, using Laser Doppler Perfusion Imaging. Blood flow recovery was impaired in VWF-/- mice. After 10 days, VWF-/- mice showed a 43 ± 5% recovery versus 68 ± 5% in WT. Immunohistochemistry revealed that both arteriogenesis in the adductor muscles and angiogenesis in the gastrocnemius muscles were reduced in VWF-/- mice. Furthermore, leukocyte infiltration in the affected adductor muscles was reduced in VWF-/- mice. Residual paw perfusion directly after artery ligation was also reduced in VWF-/- mice, indicating a decrease in pre-existing collateral arteriole density. When we quantified collateral arterioles, we observed a 31% decrease in the average number of collateral arterioles in the pia mater compared to WT mice (57 ± 3 in WT vs 40 ± 4 pial collaterals in VWF-/-). We conclude that VWF facilitates blood flow recovery in mice. VWF deficiency hampers both arteriogenesis and angiogenesis in a hindlimb ischaemia model. This is associated with impaired leukocytes recruitment and decreased pre-existing collateral density in the absence of VWF.

scholarly journals Extensive contacts between ADAMTS13 exosites and von Willebrand factor domain A2 contribute to substrate specificity

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1713-1719 ◽  
Author(s):  
Weiqiang Gao ◽  
Patricia J. Anderson ◽  
J. Evan Sadler
Keyword(s):  
Von Willebrand Factor ◽  
Plasma Proteins ◽  
Scissile Bond ◽  
Substrate Cleavage ◽  
Α Helix ◽  
Substrate Binding Sites ◽  
Von Willebrand ◽  
A2 Domain ◽  
Willebrand Factor ◽  
Specific Distance

Abstract The metalloprotease ADAMTS13 efficiently cleaves only the Tyr1605-Met1606 bond in the central A2 domain of multimeric von Willebrand factor (VWF), even though VWF constitutes only 0.02% of plasma proteins. This remarkable specificity depends in part on binding of the noncatalytic ADAMTS13 spacer domain to the C-terminal α-helix of VWF domain A2. By kinetic analysis of recombinant ADAMTS13 constructs, we show that the first thrombospondin-1, Cys-rich, and spacer domains of ADAMTS13 interact with segments of VWF domain A2 between Gln1624 and Arg1668, and together these exosite interactions increase the rate of substrate cleavage by at least approximately 300-fold. Internal deletion of Gln1624-Arg1641 minimally affected the rate of cleavage, indicating that ADAMTS13 does not require a specific distance between the scissile bond and auxiliary substrate binding sites. Smaller deletions of the P2-P9 or the P4′-P18′ residues on either side of the Tyr1605-Met1606 bond abolished cleavage, indicating that the metalloprotease domain interacts with additional residues flanking the cleavage site. Thus, specific recognition of VWF depends on cooperative, modular contacts between several ADAMTS13 domains and discrete segments of VWF domain A2.

Platelet Density-Dependent Partition of Platelet- von Willebrand Factor Between Alpha Granule and Non-Alpha Granule Pools

1987 ◽  
Vol 58 (03) ◽  
pp. 911-914 ◽  
Author(s):  
R I Parker ◽  
Brenda C Shafer ◽  
H R Gralnick
Keyword(s):  
Plasma Membrane ◽  
Von Willebrand Factor ◽  
Plasma Proteins ◽  
Buoyant Density ◽  
Membrane Permeabilization ◽  
Density Profiles ◽  
Density Dependent ◽  
Plasma Membrane Permeabilization ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryIn this study, we demonstrate that platelets contain a small hut significant amount of platelet-von Willebrand factor(vWf) not associated with α-granules. When platelets free of plasma proteins are exposed to micromolar concentrations ofdigitonin, plasma membrane permeabilization occurs without disruption of platelet granules. Employing this technique, wehave found that upon exposure of a total platelet population to 8 μM digitonin, 5% of total platelet-vWf is released into the supernatant; this occurs without release of (β-TG from α-granules. When platelets of discrete buoyant density profiles are tested, this extragranular platelet-vWf increased with decreasing platelet density. These findings suggest that a redistribution of platelet-vWf from α-granule to non-granule sites occurs coincident with a decrease inplatelet buoyant density.

More homologies among the vertebrate plasma proteins

1985 ◽  
Vol 5 (10-11) ◽  
pp. 877-884 ◽  
Author(s):  
R. F. Doolittle
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Unknown Function ◽  
Plasma Proteins ◽  
Common Ancestry ◽  
High Molecular Weight Kininogen ◽  
A Minor ◽  
Von Willebrand ◽  
Willebrand Factor

Many of the proteins of vertebrate blood plasma share common ancestry. As more sequences are reported, the network of relationships continues to expand in unexpected directions. Computer analysis now reveals that a minor plasma protein of unknown function, gamma-trace protein, is related to the kininogen family. Some other possible relationships have been uncovered also, including a resemblance between the histidine-rich hinge regions of high molecular weight kininogen and hemopexin and between Factor VIII and Von Willebrand Factor.

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