2018
DOI: 10.1126/sciadv.aaq1477
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Autoregulation of von Willebrand factor function by a disulfide bond switch

Abstract: We demonstrate mechanochemical regulation of platelet adhesion to von Willebrand factor in thrombosis and hemostasis.

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Cited by 80 publications
(85 citation statements)
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“…9 As an important carrier of coagulation factor VIII, VWF also contributes to blood coagulation. 11 VWF is synthesized by ECs and megakaryocytes and is stored as ultra large VWF multimers or high molecular weight multimers in the endothelial Weibel-Palade bodies or the platelet α-granules, respectively. 12 Plasma VWF was thought to be derived from the secretion of ECs and platelets and could be enhanced by secretagogues.…”
Section: Von Willebrand Factormentioning
confidence: 99%
“…9 As an important carrier of coagulation factor VIII, VWF also contributes to blood coagulation. 11 VWF is synthesized by ECs and megakaryocytes and is stored as ultra large VWF multimers or high molecular weight multimers in the endothelial Weibel-Palade bodies or the platelet α-granules, respectively. 12 Plasma VWF was thought to be derived from the secretion of ECs and platelets and could be enhanced by secretagogues.…”
Section: Von Willebrand Factormentioning
confidence: 99%
“…The observed thiol/disulfide exchange between ADAMTS13 and VWF may also be relevant for the recently described redox switch in VWF. The redox status of two vicinal cysteines (C1669 and C1670) affects the conformation of the A2 domain, which in turn affects VWF binding to platelet GpIbα and accessibility to the ADAMTS13 cleavage site . Regulation of this switch by a plasma reductase has been postulated .…”
Section: Discussionmentioning
confidence: 99%
“…The redox status of two vicinal cysteines (C1669 and C1670) affects the conformation of the A2 domain, which in turn affects VWF binding to platelet GpIbα and accessibility to the ADAMTS13 cleavage site. 31 Regulation of this switch by a plasma reductase has been postulated. 32 Although not the scope of the current study, it is tempting to speculate that this reductase could be ADAMTS13, which would then control VWF activity by yet another mechanism; clearly, future work with a recombinant VWF A2 domain and ADAMTS13 is required to substantiate this thought.…”
Section: Discussionmentioning
confidence: 99%
“…6 Single-cell biophysical techniques and their sensitivity have enabled quantification and unveiling of previously unknown relationships and fundamental paradigms in platelet biology and their underlying biomechanical principles with a resolution up to single-molecule level. [7][8][9][10] However, many of these single-cell techniques are still limited in their ability to scale to measure a suitably large number of individual cells and independent samples. 11 In this review, we focus on biophysical methods suitable to assess and quantify biomechanical characteristics such as elastic modulus, stiffness (or deformability), forces generated during adhesion, and spreading and contraction of single platelets in health and disease states.…”
Section: Why Should We Investigate Biomechanical Properties Of Singmentioning
confidence: 99%
“…Given the extent of cell‐to‐cell variations, rare subpopulations, and intrinsic fluctuations within biological systems, bulk population‐level experiments often conceal and average out vital causal relationships underlying the biological phenomena . Single‐cell biophysical techniques and their sensitivity have enabled quantification and unveiling of previously unknown relationships and fundamental paradigms in platelet biology and their underlying biomechanical principles with a resolution up to single‐molecule level . However, many of these single‐cell techniques are still limited in their ability to scale to measure a suitably large number of individual cells and independent samples .…”
Section: Introductionmentioning
confidence: 99%