Disease relevance of Vwf

• CONCLUSIONS: After partial hepatectomy, plasma vWf is increased, probably due to both acute-phase reaction and decreased degradation [1].
• BACKGROUND/AIMS: Von Willebrand factor (vWf) is found in high levels in plasma of patients with acute and chronic liver disease [1].
• The adhesive protein von Willebrand factor (VWF) contributes to platelet function by mediating the initiation and progression of thrombus formation at sites of vascular injury [2].
• Identification of peptides, selected by phage display technology, that inhibit von Willebrand factor binding to collagen [3].
• GK islet vascularization, labeled by von Willebrand factor, was altered after 1 month of mild hyperglycemia [4].

High impact information on Vwf

• Together, our studies demonstrate an important role for platelet vWf in initiating the platelet aggregation process under flow and challenge the currently accepted view that the vWf-GPIbalpha interaction is exclusively involved in initiating platelet aggregation at elevated shear rates [5].
• Studies of platelets congenitally deficient in von Willebrand factor (vWf) or integrin alpha(IIb)beta(3) demonstrated a key role for platelet vWf in mediating platelet tethering and translocation, whereas integrin alpha(IIb)beta(3) mediated cell arrest [5].
• Most TUNEL-positive cells were not associated with blood vessels and did not colocalize with the endothelial cell-specific antigen, von Willebrand factor [6].
• The cellular distribution of the ACE protein in the neointima was similar to that of alpha smooth muscle actin but differed from those of endothelial (von Willebrand factor) or monocytes/macrophages (ED-1) markers, demonstrating that ACE was expressed in neointimal smooth muscle cells [7].
• Endothelial damage was shown at higher homocysteine doses as reflected by circulating ACE and von Willebrand factor changes [8].

Chemical compound and disease context of Vwf

• In the absence of C6, perivascular mononuclear infiltrates of ED1(+) macrophages and CD8(+) T lymphocytes were present 7 days after transplantation, but vascular endothelial cells were quiescent, with minimal von Willebrand factor release and no evidence of alveolar hemorrhage or edema [9].
• Without vWF, as in porcine vWD or normal pigs treated with a monoclonal anti-vWF antibody, occlusive thrombi do not develop, even with luminal stenosis [10].
• Inhibition by aurintricarboxylic acid of von Willebrand factor binding to platelet GPIb, platelet retention, and thrombus formation in vivo [11].

Biological context of Vwf

• Molecular evolution of the nuclear von Willebrand factor gene in mammals and the phylogeny of rodents [12].
• Echicetin significantly prolonged the bleeding time of mice, suggesting that it may inhibit vWF binding to GPIb in vivo as well as in vitro [13].
• Histology showed iron-labeled cells around the tumor rim in labeled mice, which expressed CD31 and von Willebrand factor, indicating the transplanted cells detected in the tumor have differentiated into endothelial-like cells [14].
• The two phage clones were further used in a two-direction competition experiment with vWF. vWF was able to displace phages from collagen in a dose-dependent manner with an IC50 of 35 micrograms/mL and phages were able to inhibit vWF binding to collagen [3].
• Von Willebrand factor (vWf) is an adhesive glycoprotein known to play an important role in hemostasis and in tissue injury [15].

Anatomical context of Vwf

• Von Willebrand factor, platelets and endothelial cell interactions [2].
• These findings suggest that normal erythrocytes adhere to desmopressin-conditioned microvascular endothelium and that endothelial cell-derived vWF is involved in the erythrocyte-endothelium interaction [16].
• These results are compatible with a model for SS vasoocclusion in which extra-large vWF-mediated adhesion of deformable SS erythrocytes is the first step followed by an accelerated entrapment of dense SS erythrocytes [17].
• Previous studies of the interaction of SS deformable discocytes with endothelial monolayers or the rat ex vivo mesocecum preparation have shown adhesion that is desmopressin (dDAVP)-stimulated, von Willebrand factor (vWF)-mediated, and limited to the small venules [18].
• Desmopressin, (DDAVP; 1-desamino-8-D-arginine vasopressin) increases the release and activity of von Willebrand factor (vWF); however, its effects on the other major constituent of endothelial Weibel-Palade bodies, P-selectin, has not been investigated [19].

Associations of Vwf with chemical compounds

• Incubation of desmopressin-treated vasculature with anti-vWF antibodies resulted in a pronounced decrease in adhesion and significantly improved hemodynamic behavior of SS cells [17].
• Echicetin: a snake venom protein that inhibits binding of von Willebrand factor and alboaggregins to platelet glycoprotein Ib [13].
• To determine the role of von Willebrand factor (vWF) in adhesion of sickle (SS) erythrocytes in microvascular flow conditions, we have perfused the ex vivo mesocecum vasculature of the rat with desmopressin, an analogue of vasopressin that causes the release of endothelial vWF [17].
• In passaged cultures we ascertained vascular smooth muscle purity of > 98% by morphology; contraction to norepinephrine and angiotensin; positive immunofluorescence staining through the sixth passage with monoclonal antibodies to smooth muscle-specific alpha- and gamma-isoactins, myosin, and desmin; and the absence of von Willebrand factor [20].
• In vitro, in cultured sinusoidal endothelial cells, the diameter of sinusoidal endothelial fenestrations was significantly lower at 6 wk in thioacetamide-treated rats. von Willebrand factor was detected in the cytoplasm as granular fluorescence after 6 wk of thioacetamide treatment [21].

Other interactions of Vwf

• The proinflammatory cytokine also provoked a strong transcriptional activation of the COX-2 gene that was quite specific to the cerebral endothelium as revealed by dual labeling using an antisera directed against the von Willebrand factor [22].
• Endothelin-1 and -3 induce the release of tissue-type plasminogen activator and von Willebrand factor from endothelial cells [23].
• The role of cyclic nucleotides in the release of tissue-type plasminogen activator and von Willebrand factor [24].
• The modulation of the induced acute release of tissue-type plasminogen activator (t-PA) and of von Willebrand factor (vWF) by compounds affecting cyclic nucleotide levels was studied, using an isolated rat hindleg perfusion system [24].
• Expression of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1, 2, Tie-1, 2 and von Willebrand factor (VWF) were assayed by reverse transcriptase-mediated polymerase chain reaction (RT-PCR) [25].

Analytical, diagnostic and therapeutic context of Vwf

• We studied the effect of liver mass and remodeling on plasma and tissue vWf after partial hepatectomy [1].
• METHODS: Rats were sacrificed postoperatively at intervals ranging from 60 min to 5 days, and vWf plasma levels were measured by enzyme-linked immunosorbent assay, using rabbit anti-human vWf, and by immunoperoxidase on cryosections, using rabbit anti-vWf/factor VIII [1].
• Northern blot hybridization was prepared with a complementary DNA specific to human vWf [1].
• We conclude that endothelial adhesion of deformable SS discocytes can be demonstrated in an in vivo animal model, that this adhesion is enhanced by dDAVP (presumably related to, but not necessarily limited to the release of vWF), and that this phenomenon per se does not lead to vasoocclusion [18].
• Under the described perfusion conditions, antibodies to fibronectin and thrombospondin, as well as incubation of SS erythrocytes with anti-vWF antibodies did not affect adhesion [17].

References