Soluble CD40 ligand, soluble P-selectin and von Willebrand factor levels in subjects with prediabetes: The impact of metabolic syndrome

2012 ◽  
Vol 45 (1-2) ◽  
pp. 92-95 ◽  
Author(s):  
Halil Genc ◽  
Teoman Dogru ◽  
Serkan Tapan ◽  
Ilker Tasci ◽  
Ergun Bozoglu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Von Willebrand Factor ◽  
Cd40 Ligand ◽  
Soluble Cd40 Ligand ◽  
Soluble P ◽  
Von Willebrand ◽  
The Impact ◽  
Willebrand Factor

Soluble P-selectin, Thrombocytopenia and von Willebrand Factor in HIV Infected Patients

1997 ◽  
Vol 77 (06) ◽  
pp. 1221-1222 ◽  
Author(s):  
Andrew D Blann ◽  
Martine Seigneur ◽  
Joel Constans ◽  
Jean Luc Pellegrin ◽  
Claude Conri
Keyword(s):  
Von Willebrand Factor ◽  
Soluble P ◽  
Von Willebrand ◽  
Willebrand Factor

Endothelial CD40 Mediates Microvascular von Willebrand Factor-Dependent Platelet Adhesion Inducing Inflammatory Venothrombosis in ADAMTS13 Knockout Mice

2020 ◽  
Vol 120 (03) ◽  
pp. 466-476
Author(s):  
Sibgha Tahir ◽  
Andreas H. Wagner ◽  
Steffen Dietzel ◽  
Hanna Mannell ◽  
Joachim Pircher ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Knockout Mice ◽  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Cd40 Ligand ◽  
Inflammatory Conditions ◽  
String Formation ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Background von Willebrand factor (vWF) plays an important role in platelet activation. CD40–CD40 ligand (CD40L) induced vWF release has been described in large vessels and cultured endothelium, but its role in the microcirculation is not known. Here, we studied whether CD40 is expressed in murine microvessels in vivo, whether CD40L induces platelet adhesion and leukocyte activation, and how deficiency of the vWF cleaving enzyme ADAMTS13 affects these processes. Methods and Results The role of CD40L in the formation of beaded platelet strings reflecting their adhesion to ultralarge vWF fibers (ULVWF) was analyzed in the murine cremaster microcirculation in vivo. Expression of CD40 and vWF was studied by immunohistochemistry in isolated and fixed cremasters. Microvascular CD40 was only expressed under inflammatory conditions and exclusively in venous endothelium. We demonstrate that CD40L treatment augmented the number of platelet strings, reflecting ULVWF multimer formation exclusively in venules and small veins. In ADAMTS13 knockout mice, the number of platelet strings further increased to a significant extent. As a consequence extensive thrombus formation was induced in venules of ADAMTS13 knockout mice. In addition, circulating leukocytes showed primary and rapid adherence to these platelet strings followed by preferential extravasation in these areas. Conclusion CD40L is an important stimulus of microvascular endothelial ULVWF release, subsequent platelet string formation and leukocyte extravasation but only in venous vessels under inflammatory conditions. Here, the lack of ADAMTS13 leads to severe thrombus formation. The results identify CD40 expression and ADAMTS13 activity as important targets to prevent microvascular inflammatory thrombosis.

Multi-Cellular Activation In Vivo by Endotoxin in Humans – Limited Protection by Adenosine Infusion

2000 ◽  
Vol 84 (09) ◽  
pp. 381-387 ◽  
Author(s):  
Nailin Li ◽  
Anne Soop ◽  
Alf Sollevi ◽  
Paul Hjemdahl
Keyword(s):  
Von Willebrand Factor ◽  
Thrombin Generation ◽  
Platelet Reactivity ◽  
Adenosine Infusion ◽  
Cellular Activation ◽  
Soluble P ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Secretion

SummaryThe influence of adenosine infusion (40 µg/kg/min for 4 h) on inflammatory and hemostatic parameters was investigated in healthy males without (n = 10) or with (n = 11) intravenous endotoxin injection (4 ng/kg). Without endotoxin, adenosine elevated circulating leukocytes and circulating platelet-leukocyte aggregates. Endotoxin activated platelets and leukocytes in vivo. Platelet activation was seen as slightly increased platelet P-selectin expression, decreased platelet counts, and elevated plasma soluble P-selectin (from 39.6 ± 3.4 to 68.9 ± 6.6 ng/ml; P <0.01). Leukocyte activation was evidenced by increased CD11b expression (from MFI of 0.54 ± 0.02 to 2.21 ± 0.17; P <0.01) and plasma elastase levels (from 25.3 ± 2.5 to 169.3 ± 22.5 ng/ml; P <0.01). Endotoxin also enhanced platelet and leukocyte responsiveness to in vitro stimulation. Endotoxin induced von Willebrand factor secretion (from 92 ± 8 units to 265 ± 19 units at 4 h; P <0.001) and enhanced thrombin generation in vivo. Endotoxin induced leukocytosis and thus increased circulating platelet-leukocyte, mainly platelet-neutrophil, aggregates. Adenosine caused slight attenuation of platelet reactivity to agonist stimulation, enhanced the endotoxin-induced leukocytosis, and detained more platelet-leukocyte aggregates in circulation, but did not attenuate endotoxin-induced neutrophil elastase secretion, von Willebrand factor secretion, or thrombin generation. Thus, endotoxemia induces multi-cellular activation in vivo. Adenosine inhibits leukocyte adhesion and extravasation, and mildly attenuates platelet responsiveness and soluble P-selectin release. Adenosine has the potential of becoming a therapeutic antiinflammatory drug, but an optimal treatment strategy needs to be developed.

Relevance of Intact Von Willebrand Factor (VWF) Triplet Structure for VWF Function.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1425-1425
Author(s):  
Bruce A. Schwartz ◽  
Birte Fuchs ◽  
Christoph Kannicht ◽  
Barbera Solecka ◽  
Mario Kröning
Keyword(s):  
Von Willebrand Factor ◽  
Adamts13 Activity ◽  
Collagen Binding ◽  
Major Band ◽  
Terminal Fragment ◽  
Triplet Structure ◽  
Von Willebrand ◽  
The Impact ◽  
Willebrand Factor ◽  
Terminal Domains

Abstract Abstract 1425 Introduction: The characteristic multimer pattern of plasmatic von Willebrand factor (VWF) results from asymmetric cleavage by the processing metalloprotease ADAMTS13 between Y1605/M1606 within the VWF A2 domain. In normal plasma, characteristic species of various multimeric sizes with flanking satellite bands (triplets) encircling the major band on VWF multimer gels are present. The faster and slower migrating bands encompassing a VWF multimer lack one N-terminal fragment or possess an additional N-terminal fragment, respectively. Even though the distribution of VWF satellite bands is significantly altered in some types of von Willebrand disease (VWD) and several commercial VWF concentrates, the impact of triplet structure on VWF function has not been investigated so far. Methods: Four commercially available VWF concentrates were analyzed with respect to ADAMTS13 content as well as VWF multimer- and triplet structure using agarose gel electrophoresis. ADAMTS13 activity was quantified by the fluorescence resonance energy transfer (FRET) assay. VWF zymogram gels were used to test for ADAMTS13 activity. Samples composed of different VWF triplet distribution but comparable VWF multimers were obtained by fractionation of plasmatic VWF using heparin affinity chromatography. VWF affinity to collagen was measured by surface plasmon resonance (SPR). Results: VWF concentrates markedly differed in their content of ADAMTS13 antigen and activity. A higher ADAMTS13 content correlated with an increased portion of the proteolyzed faster migrating VWF triplet band. The degree of VWF proteolysis, i.e. lack of an additional N-terminal fragment, correlated with a decreased collagen binding level measured by SPR. Conclusion: Proteolytic cleavage of N-terminal domains of VWF resulting in a higher content of faster migrating satellite bands affects the function of VWF. The impact of VWF N-terminal domains on collagen binding and potential clinical consequences of enhanced proteolysis in commercial concentrates has to be further evaluated. Disclosures: Schwartz: Octapharma: Employment. Fuchs:Octapharma: Employment. Kannicht:Octapharma: Employment. Solecka:Octapharma: Employment. Kröning:Octapharma: Employment.

Effects of von Willebrand factor concentration and platelet collision on shear-induced platelet activation

2008 ◽  
Vol 100 (07) ◽  
pp. 60-68 ◽  
Author(s):  
Zhenyue Gao ◽  
Fang Liu ◽  
Ziqiang Yu ◽  
Xia Bai ◽  
Fengyuan Zhuang ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Von Willebrand Factor ◽  
Annexin V ◽  
Flow Chamber ◽  
Platelet Glycoprotein ◽  
High Shear ◽  
Shear Rates ◽  
Von Willebrand ◽  
The Impact ◽  
Willebrand Factor

SummaryThe binding of plasma von Willebrand factor (vWF) to platelet glycoprotein (GP) Ibα in a high shear stress field, and subsequent integrin-GPIIb/IIIa-vWF conjunction induces platelet aggregation (SIPA). However, the specific biomechanical mechanism of the vWF-GPIb interaction still remains to be elucidated. A parallel-plate rectangular flow chamber was built to simulate a stenopeic artery flow pattern. Using the flow chamber, we examined shear- induced platelet activation (SIPAct) at different vWF concentrations (5–25 µg/ml) and several simulated stenotic high shear rates. P-selectin expression on the platelets and annexin V binding to the platelets were used as two markers of platelet activation. At different localized shear rates (3,000 s-1–9,500 s-1), the percentage of annexin V and P-selectin positive cells increased from 8.3 ± 0.4% to 22.3 ± 1.8% ( p 0.05) and from 17.4 ± 0.5% to 33.5 ± 2.5% (p 0.05),respectively. As the vWF concentration increased from 5 µg/ml to 25 µg/ml, the annexinV binding rate increased from 7.2 ± 0.6% to 53.4 ± 3.8% (p 0.05), and P-selectin expression increased from 16.5 ± 1.2% to 65.9 ± 5.2% (p 0.05). A test in a uniform shear field using cone-plate viscometer rheometry showed that the platelet activation rate was proportional to the platelet concentration. This result suggests that platelet collision is one of the impact factors of SIPAct.

von Willebrand Factor, Soluble P-Selectin, Tissue Plasminogen Activator and Plasminogen Activator Inhibitor in Atherosclerosis

1995 ◽  
Vol 74 (02) ◽  
pp. 626-630 ◽  
Author(s):  
A D Blann ◽  
M Dobrotova ◽  
P Kubisz ◽  
C N McCollum
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Plasminogen ◽  
Soluble P ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Activator Inhibitor ◽  
Pai 1

SummaryTissue plasminogen activator antigen (tPA), plasminogen activator inhibitor antigen (PAI-1), soluble P-selectin and von Willebrand factor antigen (vWf) were measured by ELISA in 41 patients with peripheral vascular disease (PVD), 41 with ischaemic heart disease (IHD) and in 46 age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0002) and in patients with PVD (p = 0.0011) relative to the controls but levels did not differ between the two patients groups. Raised tPA found in both PVD (p = 0.0006) and IHD (p = 0.0061) compared to the controls also failed to differentiate the two groups of patients. Soluble P-selectin was also raised in both groups (p = 0.003 in IHD and p = 0.0102 in PVD) with no difference between the groups. There were no differences in levels of PAI-1 between the groups. In the subjects taken as a whole, there were significant Spearman’s correlations between tPA and vWf (r = 0.37, p <0.001), tPA and triglycerides (r = 0.38, p <0.001), tPA and P-selectin (r = 0.19, p = 0.032), vWf and age (r = 0.25, p = 0.005) and inversely between vWf and HDL (r = -0.25, p = 0.006). These data support the concept that increased levels of tPA may be important in atherosclerosis, and indicate that soluble P-selectin may be useful in further analysis of the role of platelets and the endothelial cell in this disease.

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