scholarly journals von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans

Blood ◽  
2015 ◽  
Vol 125 (20) ◽  
pp. 3153-3163 ◽  
Author(s):  
Alexander T. Bauer ◽  
Jan Suckau ◽  
Kathrin Frank ◽  
Anna Desch ◽  
Lukas Goertz ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Platelet Aggregation ◽  
Malignant Melanoma ◽  
Cell Activation ◽  
Fiber Formation ◽  
Endothelial Cell Activation ◽  
Tumor Patients ◽  
Key Points ◽  
Von Willebrand ◽  
Willebrand Factor

Key Points Tumor-derived VEGF-A mediates endothelial cell activation, VWF release, and platelet aggregation provoking coagulation in tumor patients. Local ADAMTS13 inhibition promotes VWF fiber formation in tumor microvessels.

The Role of von Willebrand Factor in Pre-Eclampsia

1991 ◽  
Vol 66 (05) ◽  
pp. 525-528 ◽  
Author(s):  
Frauke Bergmann ◽  
Siegfried Rotmensch ◽  
Bruce Rosenzweig ◽  
Helen How ◽  
Juan Chediak
Keyword(s):  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Cell Activation ◽  
Hematological Parameters ◽  
Disease Process ◽  
Clinical Severity ◽  
Endothelial Cell Activation ◽  
Laboratory Findings ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe von Willebrand factor (vWF) has gained considerable interest in recent years as a marker of endothelial cell activation or insult and by virtue of its interactions with platelets and vessel walls. Altered patterns of vWF multimers were found to occur frequently in patients with thrombotic thrombocytopenic purpura in the acute and chronic stages. This disorder shares some clinical and laboratory findings with pre-eclampsia, including thrombocytopenia. Recent studies have also suggested that abnormalities of endothelial cell metabolism play a central role in the pathophysiology of pre-eclampsia. In order to determine if vWF could be instrumental in the disease process and the thrombocytopenia of pre-eclampsia we analyzed the ante- and postpartum structural and functional distribution of vWF. This data was correlated with hematological parameters such as platelet counts and the clinical severity of the disease. We found no consistent changes of vWF in association with thrombocytopenia or clinical severity. However, functional vWF was lower in postpartum samples of severely affected pre-eclamptics as compared to normal controls. This finding may reflect endothelial cell exhaustion after stimulation or cellular injury. Elevated titers of fibrin split products and thrombocytopenia were evident in severe pre-eclampsia, as seen in DIC, despite factor VIII coagulant levels within the normal range. Our data is consistent with the hypothesis of endothelial cell dysfunction in pre-eclampsia. However, the mechanism of thrombocytopenia in this disorder does not appear to be related to alterations in the structure or biological function of vWF.

von Willebrand Factor Propeptide in Vascular Disorders: A Tool to Distinguish Between Acute and Chronic Endothelial Cell Perturbation

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 179-185 ◽  
Author(s):  
Jan A. van Mourik ◽  
Ria Boertjes ◽  
Inge A. Huisveld ◽  
Karin Fijnvandraat ◽  
Dasja Pajkrt ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Cell Activation ◽  
Molar Ratio ◽  
Low Grade ◽  
Endothelial Cell Activation ◽  
Endoproteolytic Cleavage ◽  
Von Willebrand ◽  
Willebrand Factor

Before de novo synthesized von Willebrand factor (vWF) leaves the endothelial cell, it undergoes endoproteolytic cleavage of its propeptide (vW antigen II). The processed vWF and propeptide are either released constitutively or, following activation of the endothelium, released through the regulated pathway. In a recent study (Borchiellini et al, Blood 88:2951, 1996), we showed that the half-life of mature vWF and of its propeptide differ fourfold to fivefold. We postulated that the molar ratio of the propeptide to mature vWF could serve as a tool to assess the extent of endothelial cell activation under physiologic and clinical conditions. To test this hypothesis, we measured mature vWF and propeptide in patients with documented acute and chronic vascular disease, including patients with thrombotic thrombocytopenic purpura (TTP), acute septicemia, and diabetes mellitus. These data were compared with experimental conditions in healthy subjects in which perturbation of the endothelium was simulated by physical exercise or by administration of 1-deamino-8-D-arginine vasopressin (DDAVP) or endotoxin. In all individuals of the latter study group, both vWF and propeptide levels were elevated during the acute phase of the experimentally induced vascular perturbation; at later time points after stimulation, only vWF levels remained elevated. In patients with sepsis and TTP, both vWF and propeptide were elevated several-fold. Thus, this pattern can readily be explained in terms of acute perturbation of the endothelium. In contrast, in patients with diabetes mellitus propeptide levels were only slightly elevated, whereas vWF levels were elevated twofold to threefold. This pattern is a typical feature of chronic, low-grade activation of the endothelium. These observations support our hypothesis that measurement of both propeptide and vWF levels allows to discriminate between chronic and acute phases of endothelial cell activation in vivo. Measurement of only vWF is less indicative in this respect.

scholarly journals von Willebrand factor propeptide in malaria: evidence of acute endothelial cell activation

2006 ◽  
Vol 133 (5) ◽  
pp. 562-569 ◽  
Author(s):  
Martine J. Hollestelle ◽  
Cynthia Donkor ◽  
Ebenezer Akrofi Mantey ◽  
Srabasti J. Chakravorty ◽  
Alister Craig ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Von Willebrand Factor Propeptide

scholarly journals Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2520-2526 ◽  
Author(s):  
SJ van Deventer ◽  
HR Buller ◽  
JW ten Cate ◽  
LA Aarden ◽  
CE Hack ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Cell Activation ◽  
Plasminogen Activator Inhibitor ◽  
Contact System ◽  
Initial Increase ◽  
Cytokine Release ◽  
Endothelial Cell Activation ◽  
System A ◽  
Von Willebrand

Abstract Endotoxemia was evoked by bolus injection of Escherichia coli endotoxin (2 ng/kg body weight) in six healthy subjects to investigate the early kinetics of cytokine release in relation to the development of clinical and hematologic abnormalities frequently seen in gram-negative septicemia. The plasma concentration of tumor necrosis factor (TNF) increased markedly after 30 to 45 minutes, and reached a maximal level after 60 to 90 minutes. In each volunteer, the initial increase of plasma interleukin 6 (IL-6) concentrations occurred 15 minutes after the initial TNF increase, and maximal IL-6 concentrations were reached at 120 to 150 minutes. A transient increase in body temperature and pulse rate occurred simultaneously with the initial TNF and IL-6 increases, whereas a significant decrease in blood pressure occurred after 120 minutes. These changes were proportional to the changes in TNF and IL-6 concentrations. Coagulation activation, as assessed by a rise of prothrombin fragments and thrombin-antithrombin III complexes, was noted after 120 minutes, in the absence of activation of the contact system. A two- to sixfold increase in the concentrations of tissue plasminogen activator (t-PA) and von Willebrand factor antigen indicated endothelial cell activation. This increase started at 120 and 90 minutes, respectively. The release of t-PA coincided with activation of the fibrinolytic pathway, as measured by plasmin-alpha 2-antiplasmin complexes. The fibrinolytic activity of t-PA was subsequently offset by release of plasminogen activator inhibitor, observed 150 minutes after the endotoxin injection, and reaching a peak at 240 minutes. No complement activation was detected. These results show that in humans endotoxin induces an early, rapidly counteracted fibrinolytic response, and a more long-lasting activation of thrombin by a mechanism other than contact system activation. In addition, our data suggest that endotoxin-induced leukopenia and endothelial cell activation are mediated by TNF.

Von Willebrand Factor Propeptide in Vascular Disorders

2001 ◽  
Vol 86 (07) ◽  
pp. 164-171 ◽  
Author(s):  
Thalia Romani de Wit ◽  
Jan van Mourik
Keyword(s):  
Vascular Disease ◽  
Von Willebrand Factor ◽  
Time Course ◽  
Cell Activation ◽  
Cellular Adhesion ◽  
Endothelial Cell Activation ◽  
Diagnostic Significance ◽  
Vascular Disorders ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryVon Willebrand factor (VWF) is a multifunctional plasma protein that plays a prominent role in haemostasis. In endothelial cells, processing of its precursor pro-VWF results in the formation of two large polypeptides, mature VWF and a propeptide. These proteins are co-secreted on an equimolar basis but are cleared from the circulation at different rates. VWF levels are frequently elevated in response to vascular disorders. Similarly, propeptide levels are increased under these conditions, although primarily in fulminant vascular disease, such as thrombotic thrombocytopenic purpura and septicemia. In chronic vascular disease, e.g. diabetes or peripheral vascular disease, propeptide levels are much less elevated. The differential response of VWF and propeptide levels to vascular disease could provide a means to assess the extent and time course of endothelial cell activation. After secretion, the propeptide may play a role in modulating cellular adhesion processes. Thus, enhanced propeptide secretion seems not to be of merely diagnostic significance.

Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2832-2839 ◽  
Author(s):  
Maha Othman ◽  
Andrea Labelle ◽  
Ian Mazzetti ◽  
Hisham S. Elbatarny ◽  
David Lillicrap
Keyword(s):  
Von Willebrand Factor ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Platelet Surface ◽  
Adenoviral Gene Transfer ◽  
Coxsackie Adenovirus Receptor ◽  
Transfer Vectors ◽  
Adenovirus Receptor ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThrombocytopenia has been consistently reported following the administration of adenoviral gene transfer vectors. The mechanism underlying this phenomenon is currently unknown. In this study, we have assessed the influence of von Willebrand Factor (VWF) and P-selectin on the clearance of platelets following adenovirus administration. In mice, thrombocytopenia occurs between 5 and 24 hours after adenovirus delivery. The virus activates platelets and induces platelet-leukocyte aggregate formation. There is an associated increase in platelet and leukocyte-derived microparticles. Adenovirus-induced endothelial cell activation was shown by VCAM-1 expression on virus-treated, cultured endothelial cells and by the release of ultra-large molecular weight multimers of VWF within 1 to 2 hours of virus administration with an accompanying elevation of endothelial microparticles. In contrast, VWF knockout (KO) mice did not show significant thrombocytopenia after adenovirus administration. We have also shown that adenovirus interferes with adhesion of platelets to a fibronectin-coated surface and flow cytometry revealed the presence of the Coxsackie adenovirus receptor on the platelet surface. We conclude that VWF and P-selectin are critically involved in a complex platelet-leukocyte-endothelial interplay, resulting in platelet activation and accelerated platelet clearance following adenovirus administration.

Sign in / Sign up

Export Citation Format

Share Document