scholarly journals Severe COVID‐19 is associated with endothelial activation and abnormal glycosylation of von Willebrand factor in patients undergoing hemodialysis

2021 ◽  
Vol 5 (6) ◽  
Author(s):  
Golzar Mobayen ◽  
Amrita Dhutia ◽  
Candice Clarke ◽  
Maria Prendecki ◽  
Stephen McAdoo ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Endothelial Activation ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Abnormal Glycosylation

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

2020 ◽  
Vol 11 ◽  
Author(s):  
Junxian Yang ◽  
Zhiwei Wu ◽  
Quan Long ◽  
Jiaqi Huang ◽  
Tiantian Hong ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Therapeutic Strategy ◽  
Endothelial Activation ◽  
Endothelial Damage ◽  
Neutrophil Extracellular Trap ◽  
Activated Neutrophils ◽  
A Disintegrin And Metalloproteinase ◽  
Von Willebrand ◽  
Willebrand Factor

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.

Changes in ADAMTS 13 Activity and Von Willebrand Factor Parameters during Acute Dengue Infection.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1492-1492
Author(s):  
Darintr Sosothikul ◽  
Panya Seksarn ◽  
Sureeporn Pongsawaluk ◽  
Jeanne M. Lusher
Keyword(s):  
Von Willebrand Factor ◽  
Cell Activation ◽  
Dengue Infection ◽  
Plasma Concentrations ◽  
Endothelial Activation ◽  
Healthy Children ◽  
Endothelial Cell Activation ◽  
Convalescent Phase ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Dengue virus causes febrile illnesses: Dengue Fever (DF) and less frequently a life-threatening illness, Dengue Hemorrhagic Fever (DHF). The pathophysiology of hemostatic defect in dengue infection is thought to relate to the direct effect of virus or cytokines on endothelial activation. To study the state of endothelial activation during dengue infection, we measured plasma levels of von Willebrand factor antigen (vWF:Ag), vWF-collagen binding assay (vWF:CBA), and ADAMTS 13 activity in 42 children (20 with DF and 22 with DHF) during 3 phases of illness: febrile, toxic, and convalescent phase. 38 healthy children comprised as controls. Our data shows that both VWF:Ag and vWF:CBA levels were significantly higher in dengue patients (p ≤ 0.001 in both DF and DHF patients) versus controls. DHF patients had significantly higher of VWF: Ag (p = 0.01, versus DF). ADAMTS 13 activity levels were significantly decreased only in DHF patients during 3 phases of the illness (febrile; mean 78%; p = 0.016, toxic; mean 68%; p<0.001 and convalescent; mean 69%; p<0.001 compared to mean 104% of the controls). Compared to DF patients, DHF patients had significantly lower plasma concentrations of ADAMTS 13 activity during the febrile, toxic and convalescent phase (p = 0.039, p = 0.002 and p =0.003, respectively). Endothelial cell activation is a hallmark of dengue infection especially in DHF patients; indicated by a significant rise in VWF:Ag and vWF:CBA and a reciprocal decline in ADAMTS 13 activity.

scholarly journals Elevated plasma von Willebrand factor levels are associated with subsequent ischemic stroke in persons with treated HIV infection

2021 ◽  
Author(s):  
Susan M Graham ◽  
Robin M Nance ◽  
Junmei Chen ◽  
Jennie Le ◽  
Dominic W Chung ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Viral Load ◽  
Hiv Infection ◽  
Von Willebrand Factor ◽  
Endothelial Activation ◽  
Apolipoprotein A1 ◽  
Soluble Cd14 ◽  
Amyloid A ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Background We assessed whether key biomarkers of endothelial activation and hemostasis/thrombosis were elevated in individuals receiving effective antiretroviral therapy (ART) in the year before ischemic stroke. Methods We conducted a case-control study nested in the CNICS cohort, comparing 42 adjudicated cases with ischemic stroke to 83 controls matched for ART regimen. Angiopoietin-1, angiopoietin-2, C-reactive protein, interleukin-6, plasminogen activation inhibitor-1, P-selectin, serum amyloid-A, soluble CD14, ICAM-1, VCAM-1, apolipoprotein A1, ADAMTS13, and von Willebrand factor (VWF) were measured in stored plasma collected before the stroke event. We used conditional logistic regression to identify associations with ischemic stroke, with and without adjustment for Atherosclerotic Cardiovascular Disease (ASCVD) and Veterans Aging Cohort Study (VACS) scores. Results After adjustment for age and sex, higher plasma viral load and higher angiopoeitin-2, soluble CD14, and VWF were associated with increased odds of ischemic stroke; higher nadir CD4 count was associated with decreased odds of ischemic stroke. VWF remained associated with subsequent ischemic stroke after adjustment for ASCVD score (adjusted odds 1.74, 95%CI 1.01–2.98 per log2 increment). In a separate model adjusting for VACS score, only VWF (adjusted odds 1.80, 95% CI 1.04–3.12 per log2 increment) was associated with subsequent ischemic stroke. In a sensitivity analysis excluding participants with viral load ≥400 copies/mL, associations between VWF and ischemic stroke were attenuated, with risk estimates ranging from 1.59–1.64 per log2 increment. Conclusions Endothelial activation and related release and attachment of VWF may play an important role in ischemic stroke among persons living with treated HIV infection.

scholarly journals Acute von Willebrand Factor Secretion from the Endothelium In Vivo: Assessment through Plasma Propeptide (vWf:AgII) Levels

1997 ◽  
Vol 77 (02) ◽  
pp. 387-393 ◽  
Author(s):  
Ulrich M Vischer ◽  
Jørgen Ingerslev ◽  
Claes B Wollheim ◽  
Jean-Claude Mestries ◽  
Dimitrios A Tsakiris ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Time Course ◽  
Plasma Concentrations ◽  
Vascular Wall ◽  
Endothelial Activation ◽  
Relative Increase ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryElevated plasma concentrations of von Willebrand factor (vWf) are increasingly recognized as a cardiovascular risk factor, and are used as a marker of endothelial activation. However, the factors which determine the rate of vWf release from the endothelium in vivo have not been defined clearly. In addition, vWf plasma levels may also be influenced by adhesion of vWf to the vascular wall or to platelets, and by its rate of degradation. The propeptide of vWf (also called vWf:AgII) is stored and released in equimolar amounts with vWf. In the present study we attempted to determine whether this propeptide could be a more reliable marker of endothelial secretion than vWf itself. To accomplish this we developed an ELISA based on monoclonal antibodies. The propeptide levels in normal plasma were found to be 0.7 µg/ml, more than 10 times lower than vWf itself. Administration of desmopressin (DDAVP) induced a rapid relative increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However, the increases in vWf and propeptide were equivalent when expressed in molar units. A time course study indicated a half-life of the propeptide of 3 h or less. In a baboon model of disseminated intravascular coagulation (DIC) induced by FXa, vWf increased by less than 100%, whereas the propeptide concentrations increased by up to 450%. In view of the massive thrombin generation (as assessed by fibrinogen depletion), the increases in vWf are small, compared to the strong secretory response to thrombin and fibrin previously observed in vitro. Our results suggest that due to its rapid turnover, the propeptide could provide a sensitive plasma marker of acute endothelial secretion.

Fluvastatin Decreases Soluble Thrombomodulin in Cardiac Transplant Recipients

2000 ◽  
Vol 83 (01) ◽  
pp. 46-48 ◽  
Author(s):  
Marie-Françoise Aillaud ◽  
Gilbert Habib ◽  
Bernard Kreitmann ◽  
Dominique Métras ◽  
Roger Luccioni ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Endothelial Activation ◽  
Cardiac Transplant ◽  
Transplant Recipients ◽  
Rapid Improvement ◽  
Double Blind ◽  
Soluble Thrombomodulin ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Pai 1

SummaryWe conducted a randomized, placebo controlled, double-blind, cross-over study, to assess the effects of a 4-week fluvastatin therapy on plasma markers of endothelial activation or injury in 20 transplanted heart recipients. The levels of thrombomodulin and von Willebrand factor antigen were higher at baseline in cardiac transplant recipients than in age and sex-matched healthy controls. Plasma total cholesterol showed a 21% reduction on fluvastatin therapy (p = 0.0001). Fluvastatin treatment had no significant effect on creatininemia, plasma cyclosporine, PAI-1 antigen, PAI-1 activity, tPA antigen, and Von Willebrand factor. However, fluvastatin produced a significant decrease of plasma thrombomodulin (66.7 ng/ml on placebo versus 58.8 ng/ml on fluvastatin, p <0.001), suggesting a rapid improvement of endothelial injury in these patients.

Phospholipase D1 is specifically required for regulated secretion of von Willebrand factor from endothelial cells

Blood ◽  
2009 ◽  
Vol 113 (4) ◽  
pp. 973-980 ◽  
Author(s):  
Jennifer Disse ◽  
Nicolas Vitale ◽  
Marie-France Bader ◽  
Volker Gerke
Keyword(s):  
Endothelial Cells ◽  
Plasma Membrane ◽  
Von Willebrand Factor ◽  
Inflammatory Responses ◽  
Endothelial Activation ◽  
Tissue Type ◽  
Type Plasminogen Activator ◽  
Phospholipase D1 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractEndothelial cells regulate thrombosis, hemostasis, and inflammatory responses by supplying the vasculature with several factors that include procoagulant von Willebrand factor (VWF) and fibrinolytic tissue-type plasminogen activator (tPA). Both proteins can be secreted in a Ca2+-regulated manner after endothelial activation but exhibit opposing physiologic effects. In search for factors that could modulate endothelial responses by selectively affecting the secretion of procoagulant or anticoagulant proteins, we identify here phospholipase D1 (PLD1) as a specific regulator of VWF secretion. PLD1 is translocated to the plasma membrane upon stimulation of endothelial secretion, and this process correlates with the generation of phosphatidic acid (PA) in the plasma membrane. Histamine-evoked secretion of VWF, but not tPA, is inhibited by blocking PLD-mediated production of PA, and this effect can be attributed to PLD1 and not PLD2. Thus, different mechanisms appear to control the agonist-induced secretion of VWF and tPA, with only the former requiring PLD1.

Sign in / Sign up

Export Citation Format

Share Document