Marked Temperature Dependence of the Platelet Calcium Signal Induced by Human von Willebrand Factor

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 199-207 ◽  
Author(s):  
John C. Kermode ◽  
Qi Zheng ◽  
Elizabeth P. Milner
Keyword(s):  
Arachidonic Acid ◽  
Temperature Dependence ◽  
Von Willebrand Factor ◽  
Thromboxane A2 ◽  
Underlying Mechanism ◽  
Calcium Signal ◽  
Free Calcium ◽  
Strong Temperature Dependence ◽  
Von Willebrand ◽  
Willebrand Factor

Interaction of von Willebrand factor (vWF) with the platelet is essential to hemostasis when vascular injury occurs. This interaction elevates the intracellular free calcium concentration ([Ca2+]i) and promotes platelet activation. The present study investigated the temperature dependence of vWF-induced [Ca2+]i signaling in human platelets. The influence of temperature can provide invaluable insight into the underlying mechanism. Platelet [Ca2+]i was monitored with Fura-PE3. Ristocetin-mediated binding of vWF induced a transient platelet [Ca2+]i increase at 37°C, but no response at lower temperatures (20°C to 25°C). This temperature dependence could not be attributed to a reduction in vWF binding, as ristocetin-mediated platelet aggregation and agglutination were essentially unaffected by temperature. Most other platelet agonists (U-46619, -thrombin, and adenosine 5′-diphosphate [ADP]) induced a [Ca2+]isignal whose amplitude did not diminish at lower temperatures. The [Ca2+]i signal in response to arachidonic acid, however, showed similar temperature dependence to that seen with vWF. Assessment of thromboxane A2 production showed a strong temperature dependence for metabolism of arachidonic acid by the cyclo-oxygenase pathway. vWF induced thromboxane A2production in the platelet. Aspirin treatment abolished the vWF-induced [Ca2+]i signal. These observations suggest that release of arachidonic acid and its conversion to thromboxane A2 play a central role in vWF-mediated [Ca2+]i signaling in the platelet at physiological temperatures.

Epinephrine Induces von Willebrand Factor Release from Cultured Endothelial Cells: Involvement of Cyclic AMP-dependent Signalling in Exocytosis

1997 ◽  
Vol 77 (06) ◽  
pp. 1182-1188 ◽  
Author(s):  
Ulrich M Vischer ◽  
Claes B Wollheinn
Keyword(s):  
Endothelial Cells ◽  
Adenylate Cyclase ◽  
Von Willebrand Factor ◽  
Umbilical Vein ◽  
Free Calcium ◽  
Camp Content ◽  
Von Willebrand ◽  
Willebrand Factor

Summaryvon Willebrand factor (vWf) is released from endothelial cell storage granules after stimulation with thrombin, histamine and several other agents that induce an increase in cytosolic free calcium ([Ca2+]i). In vivo, epinephrine and the vasopressin analog DDAVP increase vWf plasma levels, although they are thought not to induce vWf release from endothelial cells in vitro. Since these agents act via a cAMP-dependent pathway in responsive cells, we examined the role of cAMP in vWf secretion from cultured human umbilical vein endothelial cells. vWf release increased by 50% in response to forskolin, which activates adenylate cyclase. The response to forskolin was much stronger when cAMP degradation was blocked with IBMX, an inhibitor of phosphodiesterases (+200%), whereas IBMX alone had no effect. vWf release could also be induced by the cAMP analogs dibutyryl-cAMP (+40%) and 8-bromo-cAMP (+25%); although their effect was weak, they clearly potentiated the response to thrombin. Epinephrine (together with IBMX) caused a small, dose-dependent increase in vWf release, maximal at 10-6 M (+50%), and also potentiated the response to thrombin. This effect is mediated by adenylate cyclase-coupled β-adrenergic receptors, since it is inhibited by propranolol and mimicked by isoproterenol. In contrast to thrombin, neither forskolin nor epinephrine caused an increase in [Ca2+]j as measured by fura-2 fluorescence. In addition, the effects of forskolin and thrombin were additive, suggesting that they act through distinct signaling pathways. We found a close correlation between cellular cAMP content and vWf release after stimulation with epinephrine and forskolin. These results demonstrate that cAMP-dependent signaling events are involved in the control of exocytosis from endothelial cells (an effect not mediated by an increase in [Ca2+]i) and provide an explanation for epinephrine-induced vWf release.

A role for p38 MAP kinase in platelet activation by von Willebrand Factor

2004 ◽  
Vol 91 (01) ◽  
pp. 102-110 ◽  
Author(s):  
Ilaria Canobbio ◽  
Stefania Reineri ◽  
Fabiola Sinigaglia ◽  
Cesare Balduini ◽  
Mauro Torti
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Map Kinase ◽  
Platelet Activation ◽  
Von Willebrand Factor ◽  
P38 Map Kinase ◽  
Cyclooxygenase Inhibitors ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Stimulation Of

SummaryPlatelet activation induced by von Willebrand factor (VWF) binding to the membrane GPIb-IX-V receptor involves multiple signal transduction pathways. Among these, recruitment and activation of the FcγRIIA and stimulation of phospholipase A2 represent independent events equally essential to support a complete platelet response. Phospholipase A2 is activated by calcium and by phosphorylation through MAP kinases. In this work, we found that VWF stimulated the rapid and sustained phosphorylation of p38 MAP kinase (p38MAPK). In vitro kinase assay revealed that VWF-stimulated phosphorylation of p38MAPK was associated with increased kinase activity. Binding of VWF to GPIb-IX-V, but not to integrin αIIbβ3, was required to support phosphorylation of p38MAPK. Neither the blockade of the membrane FcγRIIA by a specific monoclonal antibody or the prevention of thromboxane A2 synthesis by cyclooxygenase inhibitors affected VWF-induced p38MAPK activation. However, phosphorylation of p38MAPK was prevented by the tyrosine kinase Syk inhibitor piceatannol. Treatment of platelets with the p38MAPK inhibitor SB203580 totally prevented VWFstimulated platelet aggregation. Moreover, release of arachidonic acid induced by VWF was strongly impaired by inhibition of p38MAPK. We also found thatVWF induced phosphorylation of cytosolic phospholipase A2, and that this process was prevented by the p38MAPK inhibitor SB203580.These results demonstrate that p38MAPK is a key element in the FcγRIIA-independent pathway for VWF-induced platelet activation, and is involved in the stimulation of phospholipase A2 and arachidonic acid release.

Inhibitory Effect of Prostacyclin and Nitroprusside on Type IIB von Willebrand Factor-promoted Platelet Activation

1996 ◽  
Vol 76 (03) ◽  
pp. 469-474 ◽  
Author(s):  
Mariangela Francesconi ◽  
Alessandra Casonato ◽  
Stefano Pagan ◽  
Arianna Donella-Deana ◽  
Elena Pontara ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Tyrosine Phosphorylation ◽  
Platelet Activation ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Protein Tyrosine ◽  
Platelet Receptor ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryVon Willebrand disease (vWD) of type IIB is a hereditary haemorragic disorder characterised by an excessive interaction of von Willebrand factor (vWF) with the platelet receptor GPIb which promotes platelet activation and aggregation through a phospholipase A2-mediated release of arachidonic acid.The present report shows that prostacyclin and nitroprusside, vaso-dilator-compounds that enhance the cAMP and cGMP concentration respectively, cause a drastic inhibition of the type IIB vWF-induced platelet responses including increase of cytosolic Ca2+ concentration, phosphorylation of pleckstrin (47 kDa) and myosin light chain (20 kDa), secretion of ATP and serotonin, and aggregation parallel to a decrease of arachidonic acid release. Type IIB vWF also elicits tyrosine phosphorylation of proteins with apparent molecular mass of 60,74,82 and 130 kDa. Prostacyclin, which induces per se tyrosine-phosphoryla-tion of proteins of about 38 and 45 kDa, inhibits drastically the type IIB vWF-promoted tyrosine-phosphorylation of the 74 kDa protein while inhibits slightly that of 60 kDa band. The protein tyrosine-kinase inhibitor genistein causes a little decrease in the type IIB vWF-induced release of arachidonic acid.It is concluded that the inhibition exerted by prostacyclin and nitroprusside on type IIB vWF-elicited platelet activation seems to be largely ascribable to prevention of the phospholipase A2 activation with the ensuing decrease of the subsequent protein tyrosine phosphorylation

Increased Level of von Willebrand Factor Is Significantly and Independently Associated with Diabetes in Postinfarction Patients

2001 ◽  
Vol 86 (09) ◽  
pp. 791-799 ◽  
Author(s):  
George Pancio ◽  
Arthur Moss ◽  
Vijay Kalaria ◽  
Victor Marder ◽  
Harvey Weiss ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Hdl Cholesterol ◽  
Plasminogen Activator Inhibitor ◽  
Underlying Mechanism ◽  
Endothelial Damage ◽  
Factor Vii ◽  
Cardiac Events ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Pai 1

SummaryDiabetes is an established risk factor for reinfarction and cardiac death in postinfarction patients. Since the underlying mechanism of diabetes-related risk is not fully understood we aimed to evaluate the association between lipids, thrombogenic factors and diabetes in postinfarction patients. The study population consisted of 1,045 post-infarction patients (846 non-diabetic, 125 non-insulin- and 74 insulin-requiring diabetics) with the following blood tests performed 2 months after an index myocardial infarction: lipoprotein (a), apolipoprotein-B, apolipoprotein-A, cholesterol, HDL cholesterol, triglycerides, insulin, von Willebrand factor (vWF), fibrinogen, factor VII, D-dimer, and plasminogen activator inhibitor (PAI-1). After adjustment for relevant clinical covariates, non-insulin-requiring diabetes was significantly (p <0.05) associated with elevated levels of (odd ratios per 1 log unit increase in parenthesis) vWF (1.74) and PAI-1 (1.42) whereas insulin requiring diabetes was associated with even more elevated levels of vWF (4.68), but not with increased levels of PAI-1. No significant differences in lipid levels were observed among three groups. In conclusion, increased level of von Willebrand factor is significantly and independently associated with diabetes in postinfarction patients, suggesting that endothelial damage is the primary mechanisms contributing to an increased occurrence of vascular and cardiac events in diabetic postinfarction patients.

scholarly journals Temperature-Dependence of Weibel-Palade Body Exocytosis and Cell Surface Dispersal of von Willebrand Factor and Its Propolypeptide

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27314 ◽  
Author(s):  
Lindsay Hewlett ◽  
Gregor Zupančič ◽  
Gregory Mashanov ◽  
Laura Knipe ◽  
David Ogden ◽  
...  
Keyword(s):  
Cell Surface ◽  
Temperature Dependence ◽  
Von Willebrand Factor ◽  
Von Willebrand ◽  
Willebrand Factor
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