Disease relevance of VWF

• Von Willebrand disease (VWD) is an inherited bleeding disorder, caused by quantitative (type 1 and 3) or qualitative (type 2) defects in von Willebrand factor (VWF) [1].
• Gene therapy is an appealing strategy for treatment of VWD because it is caused by a single gene defect and because VWF is secreted into the circulation, obviating the need for targeting specific organs or tissues [1].
• These data indicate that platelet glycoprotein Ib-von Willebrand factor interactions are important during coronary occlusion and that aurintricarboxylic acid can inhibit coronary thrombosis associated with coronary constriction [2].
• Group 3 received homologous purified factor VIII/von Willebrand factor protein (F VIII/vWF) after glass-wool filtration but before induction of ischemia; Group 4 received F VIII/vWF-poor cryoprecipitate at the same time point [3].
• Under high shear arterial blood flow von Willebrand Factor (vWF) binds the platelet receptor glycoprotein (GP) Ibalpha, leading to platelet adhesion, activation and thrombosis [4].

High impact information on VWF

• Von Willebrand factor and platelet membrane glycoprotein Ib receptors interact to mediate platelet adhesion and thrombogenesis in stenosed and endothelium-injured arteries [5].
• In this study, a gene-based approach for VWD was developed using lentiviral transduction of blood-outgrowth endothelial cells (BOECs) to express functional VWF [1].
• Influence of factor VIII/von Willebrand factor protein (F VIII/vWF) and F VIII/vWF-poor cryoprecipitate on post-ischemic microvascular reperfusion in the central nervous system [3].
• In the 5 affected dogs tested, platelet counts and measurements of plasma coagulant function and von Willebrand factor were normal [6].
• Evaluation of the buccal bleeding time and platelet glass bead retention as assays of hemostasis in the dog: the effects of acetylsalicylic acid, warfarin and von Willebrand factor deficiency [7].

Chemical compound and disease context of VWF

• Effect of desmopressin on von Willebrand factor multimers in Doberman Pinschers with type 1 von Willebrand disease [8].
• Plasma von Willebrand factor antigen concentration was measured in 10 dogs with hypothyroidism, before and after administration of a replacement dose of levothyroxine for 67 +/- 12 days [9].
• Infusion of the vasopressin analogue DDAVP into five normal dogs at doses of 0.1-2.0 micrograms DDAVP per kg body weight induced dose-dependent increases in the plasma content of coagulation factor VIII and von Willebrand factor [10].

Biological context of VWF

• We investigated the applicability of chimeraplasty to correct a point mutation in the von Willebrand Factor (VWF) gene resulting in a von Willebrand Disease (VWD) type 3 phenotype [11].
• However, this apparent conversion is very likely not the result of RDO-mediated nucleotide conversion as the same VWF type 3 DNA sequence was also detected in negative control experiments where no RDO was used [11].
• RDOs to convert the wild type VWF gene into VWD type 3 gDNA were constructed and used in various transfection conditions [11].
• Platelet counts, clotting times and Von Willebrand's factor (VWF) assays were assessed in all dogs [12].
• Shear stress appears to induce platelet aggregation in vitro by means of initiation of von Willebrand factor binding to platelet glycoprotein Ib [2].

Anatomical context of VWF

• RESULTS: There were significantly more microvessels positive for VWF in the adventitia of skeletonized ITAs than in the adventitia of pedicled ITAs but the expression of PCNA in both groups was minimal, as in normal vessels. iNOS was not detected in any specimen [13].
• Counts of von Willebrand factor-positive microvessels and smooth muscle alpha-actin-positive arterioles demonstrated that the angiogenesis and ateriogenesis was promoted in the laser group and correlated directly with the number of MMP-stained microvessels [14].
• Immunofluorescent staining with antibodies to von Willebrand factor and ultrastructural analysis with an electron microscope confirmed the endothelial character of these cells lining the lumen of the skeletal muscle ventricles [15].
• We determined whether administration of cryoprecipitate or fresh-frozen plasma (FFP) would enhance glass bead platelet retention and shorten the bleeding time in von Willebrand factor (vWf)-deficient Doberman Pinschers [16].
• Constitutive release and intracellular content of vWf in cultured EC from femoral veins was about 30 times higher than that from femoral arterial EC, which was barely detectable [17].

Associations of VWF with chemical compounds

• The VWF was denatured to varying degrees by exposure to temperature and pH extremes, low ionic strength, and 6 M urea [18].
• This effect is mediated by aurintricarboxylic acid binding to von Willebrand factor; this binding results in inhibition of von Willebrand factor interaction with glycoprotein Ib [2].
• We evaluated the effect of aurintricarboxylic acid (ATA), a triphenyl dye that blocks von Willebrand factor (vWF) binding to platelet glycoprotein Ib, on arterial reperfusion and acute rethrombosis following fibrinolytic therapy [19].
• We employed the widely applied tetracycline-controlled transactivator system (tTA) to study the regulation of vWF mRNA synthesis in stably transfected Madin Darby kidney (MDCK-II) cells in a quantitative manner [20].
• Pretreatment with SR 49059 (1 mg/kg I.V.) and SR 27417 (a platelet-activating factor receptor antagonist) (1 mg/kg I.V.) had no effect on the DDAVP-induced (1 microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels [21].

Other interactions of VWF

• Double staining showed co-localization of beta-actin protein and von Willebrand factor, a specific endothelial cell marker [22].
• The panel included vimentin, desmin, Myo D1, smooth muscle actin, cytokeratin, S100, von Willebrand factor (factor VIII), Mac 387, CD3, major histocompatibility complex (MHC) class II, and CD79a [23].
• Immunohistochemical labeling for von Willebrand factor, tissue factor, factor XII, tissue factor pathway inhibitor, thrombomodulin, protein C, protein S and prothrombin activation fragment F1 + 2 was performed [24].
• The influence of preadsorbed canine von Willebrand factor, fibronectin and fibrinogen on ex vivo artificial surface-induced thrombosis [25].

Analytical, diagnostic and therapeutic context of VWF

• After observation with confocal laser scanning microscopy, quantitative analyses of the staining signal for VWF and eNOS expressed on endothelial cells were performed [13].
• On the other hand, sequence analysis of isolated DNA of transfected cells did reveal the presence of VWF type 3 DNA [11].
• There was a significant increase in the density of microvessels per squared millimeter in the infarcted regions of the EECP group compared with the control group (vWF, 15.2 +/- 6.3 vs. 4.9 +/- 2.1, P < 0.05; alpha-actin, 11.8 +/- 5.3 vs. 3.4 +/- 1.2, P < 0.05) [26].
• However, in the superficial endarterectomy group scanning electron microscopy showed scattered areas of factor VIII/von Willebrand factor (FVIII/vWF)-negative, endothelial-like cells at 4 weeks, whereas at 8 weeks most of the surface was covered by endothelial cells identified by FVIII/vWF [27].
• Immunofluorescence staining with anti-vWF antibodies revealed that increasing the concentration of tetracycline resulted in a decreased number of MDCK-II cells that synthesize vWF [20].

References