scholarly journals Risk stratification and prognostic evaluation of endothelial cell‑specific molecule1, von Willebrand factor, and a disintegrin‑like and metalloprotease with thrombospondin type 1 motif for sepsis in the emergency department: An observational study

2019 ◽  
Author(s):  
Qing Zhang ◽  
Chun‑Sheng Li
Keyword(s):  
Emergency Department ◽  
Endothelial Cell ◽  
Observational Study ◽  
Risk Stratification ◽  
Von Willebrand Factor ◽  
Prognostic Evaluation ◽  
Von Willebrand ◽  
Willebrand Factor

Glycoprotein Ib Can Mediate Endothelial Cell Attachment to a von Willebrand Factor Substratum

1995 ◽  
Vol 73 (02) ◽  
pp. 309-317 ◽  
Author(s):  
Dorothy A Beacham ◽  
Miguel A Cruz ◽  
Robert I Handin
Keyword(s):  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Cell Attachment ◽  
Umbilical Vein ◽  
Single Amino Acid ◽  
Cell Surface Expression ◽  
Platelet Glycoprotein ◽  
Glycoprotein Ib ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryIntroduction of single amino acid substitutions into the C-terminal Arg-Gly-Asp-Ser (RGDS) site of von Willebrand Factor, referred to as RGD mutant vWF, selectively abrogated vWF binding to platelet glycoprotein IIb/IIIa (GpIIb/IIIa, αIIbβ3 and abolished human umbilical vein endothelial cell (HUVEC) spreading, but not attachment, to RGD mutant vWF (Beacham, D. A., Wise, R. J., Turci, S. M. and Handin, R. I. 1992. J. Biol. Chem. 167, 3409-3415). These results suggested that in addition to the vitronectin receptor (VNR, αvβ3), a second endothelial membrane glycoprotein can mediate HUVEC adhesion to vWF. HUVEC attachment to wild-type (WT) and RGD-mutant vWF was reduced by two proteins known to block the vWF-platelet glycoprotein Ib/IX (GpIb/IX) interaction, the monoclonal antibody AS-7 and the recombinant polypeptide, vWF-A1. The addition of cytochalasin B or DNase I to disrupt potential GPIbα-cytoskeletal interactions enhanced the immunoprecipitation of endothelial GPIbα, caused HUVEC to round up, and increased HUVEC adhesion to RGD mutant vWF. These results indicate that while the VNR is the primary adhesion receptor for vWF, endothelial GPIbα can mediate HUVEC attachment to vWF. GpIb-dependent attachment could contribute to HUVEC adhesion under conditions when cell surface expression of the VNR is downregulated, and VNR-dependent adhesion is reduced.

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

2021 ◽  
Vol 47 (02) ◽  
pp. 192-200
Author(s):  
James S. O'Donnell
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Personalized Treatment ◽  
Treatment Plans ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

Effect of the Antioxidants Selenium and Beta-carotene on HIV-related Endothelium Dysfunction

1998 ◽  
Vol 80 (12) ◽  
pp. 1015-1017 ◽  
Author(s):  
M. Seigneur ◽  
A. D. Blann ◽  
M. Renard ◽  
F. Resplandy ◽  
J. Amiral ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Inflammatory Markers ◽  
Beta Carotene ◽  
Soluble Thrombomodulin ◽  
Endothelium Dysfunction ◽  
Increased Risk ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryPatients infected with HIV are at increased risk of atherosclerosis, and have evidence of endothelium dysfunction. The hypothesis was tested that HIV-related endothelium dysfunction is related to loss of antioxidants. This was done by the supplementation of the antioxidants selenium and beta-carotene. We supplemented the diet of 10 HIV-sero-positive subjects with 100 μg selenium daily, 11 subjects with 30 mg beta-carotene twice daily while 15 subjects were not supplemented. Plasma was obtained at outset and after a year, and tested by ELISA for endothelial cell, platelet and inflammatory markers.The non-supplemented patients experienced increases in von Wille-brand factor and soluble thrombomodulin (both p < 0.01). There were no changes in any of the indices in the patients taking selenium or beta-carotene.Increased von Willebrand factor and soluble thrombomodulin in the non-supplemented patients imply increased damage to the endothelium over the year of the study. Therefore we interpret the lack of increase in the patients taking antioxidants as evidence of the protection of the endothelium by these agents.

Von Willebrand’s Disease caused by Compound Heterozygosity for a Substitution Mutation (T1156M) in the D3 Domain of the Von Willebrand Factor and a Stop Mutation (Q2470X)

2002 ◽  
Vol 88 (09) ◽  
pp. 421-426 ◽  
Author(s):  
Stefan Lethagen ◽  
Christina Isaksson ◽  
Charlotta Schaedel ◽  
Lars Holmberg
Keyword(s):  
Von Willebrand Factor ◽  
Null Allele ◽  
Dependent Manner ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Stop Mutation ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryHereditary defects of the von Willebrand factor (VWF) gene cause von Willebrand’s disease (VWD) which shows great variability dependent on the nature and location of the mutation. We here describe the characteristics of a substitution of methionine for threonine 1156 in the D3 domain of the VWF, i.e. the domain involved in the intracellular multimerization of pro-VWF dimers. A VWD patient with severe symptoms was a compound heterozygote for the T1156M mutation and a null allele (Q2470X) on the other chromosome. This led to marked reduction of plasma VWF concentration to about 0.05 U/ml and an abnormality of VWF multimers as in type 2A VWD. Expression in vitro of the mutation demonstrated that 1156M-VWF is secreted from COS-7 cells in a much reduced amount and lacking large multimers. When coexpressed with normal VWF 1156M-VWF decreased the secretion of normal VWF in a dose-dependent manner, the secreted VWF showing all the multimers. Two relatives of the propositus were single heterozygotes for the T1156M mutation and were either asymptomatic or had the manifestations of mild type 1 VWD. The expression data and studies of platelet VWF indicate that the T1156M mutation results in intracellular retention of VWF rather than impaired synthesis. Three other members of the family were heterozygotes for the Q2470X mutation and demonstrated the variable expressivity of a null allele.

scholarly journals An apparently silent nucleotide substitution (c.7056C>T) in the von Willebrand factor gene is responsible for type 1 von Willebrand disease

Haematologica ◽  
2011 ◽  
Vol 96 (6) ◽  
pp. 881-887 ◽  
Author(s):  
V. Daidone ◽  
L. Gallinaro ◽  
M. Grazia Cattini ◽  
E. Pontara ◽  
A. Bertomoro ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Nucleotide Substitution ◽  
Von Willebrand Disease ◽  
Factor Gene ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Role of plasma viscosity in platelet adhesion

Blood ◽  
1992 ◽  
Vol 80 (4) ◽  
pp. 953-959 ◽  
Author(s):  
HF van Breugel ◽  
PG de Groot ◽  
RM Heethaar ◽  
JJ Sixma
Keyword(s):  
Endothelial Cell ◽  
Shear Rate ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Human Albumin ◽  
Plasma Viscosity ◽  
Cell Matrix ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Medium Viscosity

Abstract Platelet adhesion to the vessel wall is initiated by transport of blood platelets from the bulk flow to the wall. The process of diffusion and convection of the platelets is affected by rheological conditions such as well shear rate, red blood cell (RBC) deformability, and viscosity of the medium. To study the effect of plasma viscosity on platelet adhesion, perfusion experiments with a rectangular perfusion chamber were performed. Reconstituted blood, consisting of washed platelets and washed RBCs, was circulated through this chamber for 5 minutes at a wall shear rate of 300 s-1. Different albumin concentrations were made, to obtain different medium viscosities (0.89 to 1.85 mPa.s). Platelet adhesion decreased with increasing medium viscosity up to viscosities of 0.95 mPa.s, but increased with medium viscosity above this value. Instead of human albumin solution, different plasma viscosities were obtained by dilution of Waldenstrom plasma with buffer. Plasma was depleted of fibronectin, which gave a final plasma viscosity of 2.0 mPa.s, and was dialyzed against HEPES buffer and subsequently diluted with the dialysis buffer in different fractions (0.89 to 2.00 mPa.s). Perfusions were performed over a purified von Willebrand factor coating on glass, or over an endothelial cell matrix, preincubated with von Willebrand factor. With both surfaces, platelet adhesion was dependent on the plasma viscosity in a similar way: at low plasma viscosities, adhesion was decreased with increasing plasma viscosity, while at higher plasma viscosities, adhesion increased with plasma viscosity. Adhesion values at higher plasma viscosity or at higher human albumin concentrations could be explained by effects of the medium on the rigidity of the RBCs, since platelet adhesion is known to be increased by enhanced RBC rigidity. Effects of the medium on the deformability of the RBCs were measured separately with the laser diffraction method. These experiments confirmed that presence of human albumin or plasma in the measuring suspension increased the rigidity of RBCs. To prevent influence of the medium on the RBCs in perfusion experiments, the RBCs were fixated with glutaraldehyde. Perfusion experiments with fixated RBCs in plasma over a von Willebrand factor preincubated endothelial cell matrix, showed a consequent decrease in adhesion with increasing plasma viscosity, according to the diffusion theories, whereas the increase of adhesion at high plasma viscosities was lacking. This suggests that the latter effect was entirely due to increased transport of platelets by more rigid RBCs.

PERTURBATION OF CULTURED ENDOTHELIAL CELLS ALTERS CELLULAR VON WILLEBRAND FACTOR DISTRIBUTION

1987 ◽  
Author(s):  
J H Reinders ◽  
C L Verweii ◽  
J A V Mourlk ◽  
Ph G de Groot
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Phorbol Esters ◽  
Term Treatment ◽  
Cellular Distribution ◽  
Long Term Treatment ◽  
Von Willebrand ◽  
Willebrand Factor

Endothelial cells, cultured from human umbilical veins, synthesize von Willebrand Factor (vWF), that is stored by the cells in Weibel-Palade bodies, secreted into the medium and incorporated into the extracellular matrix underneath the cells. We have studied the influence of perturbation by phorbol esters and thrombin on the cellular distribution of vWF. Short-term (< 1 hour) treatment of endothelial cells with phorbol ester PMA or thrombin resulted in the release of cellular stored vWF. Long-term treatment with perturbants evoked a distinct change in the endothelial cell distribution of vWF, evident 24 to 48 hours after exposure. While the contents of the vWF storage vesicles were gradually restored within 48 hours, enhanced amounts of vWF were secreted into the medium. However, PMA did not increase the endothelial cell contents of mRNA encoding for vWF. The number as well as the size of vWF storage granules in the cells increased after exposure to perturbants. The perturbed cells responded to stimuli in releasing stored vWF, the amounts secreted were even greater than those in control cells. The extracellular matrix lost its vWF contents as the result of PMA or thrombin treatment, by blocking deposition of vWF in the matrix, not by enhancing degradation of matrix vWF. In perfusion experiments, the adhesion of washed platelets onto the isolated matrix of perturbed cells was considerable less than that in controls. Addition of vWF to the perfusate overcame this impairment. Thus, perturbation of endothelial cells changes the cellular distribution of vWF.Supported in part by ZWO grants 13-30-31 and 13-90-91 and Netherlands Heart Foundation grant 28.004.

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