235 Cyclic-AMP elevating agents induce acute release of tissue-type plasminogen activator and von Willebrand factor from human endothelial cells

1996 ◽  
Vol 10 ◽  
pp. 68
Keyword(s):  
Endothelial Cells ◽  
Cyclic Amp ◽  
Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Tissue Type ◽  
Human Endothelial Cells ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Von Willebrand ◽  
Willebrand Factor

Adenosine 3’:5’-Cyclic Monophosphate Induces Regulated Secretion of Tissue-Type Plasminogen Activator and von Willebrand Factor from Cultured Human Endothelial Cells

1998 ◽  
Vol 79 (04) ◽  
pp. 853-858 ◽  
Author(s):  
R. J. Hegeman ◽  
van den Eijnden-Schrauwen ◽  
J. J. Emeis
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Regulated Secretion ◽  
Cyclic Monophosphate ◽  
Type Plasminogen Activator ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe effect of compounds increasing intracellular adenosine 3’:5’-cyclic monophosphate [cAMP]i levels (prostacyclin, isoproterenol, forskolin, cholera toxin), and of the cAMP analogs 8-bromo-cAMP and dibutyryl-cAMP, on the regulated secretion (acute release) of tissue-type plasminogen activator (tPA) and von Willebrand factor (vWF) was studied in cultured human umbilical vein endothelial cells (HUVEC).Prostacyclin, isoproterenol and forskolin, which increased [cAMP]i in HUVEC, and the cell-permeant cAMP analog 8-bromo-cAMP induced dose- and time-dependent secretion of tPA and vWF. The extent of vWF and tPA release correlated with [cAMP]i, and was increased by the phosphodiesterase inhibitor isobutylmethylxanthine.In contrast to thrombin, the cAMP-elevating agents did not increase the intracellular calcium concentration [Ca2+]i in HUVEC. At sub-maximal concentrations, the effects of thrombin and prostacyclin were additive.Our results show that an increase in [cAMP]i resulted in regulated secretion (acute release) of tPA and vWF from HUVEC, without the concomitant increase in [Ca2+]i which is, in HUVEC, essential for thrombin-induced regulated secretion to occur. cAMP-induced secretion represents a novel mechanism for causing regulated secretion of tPA and vWF from endothelial cells.

The Simultaneous Acute Release of Tissue-Type Plasminogen Activator and von Willebrand Factor in the Perfused Rat Hindleg Region

1990 ◽  
Vol 63 (03) ◽  
pp. 454-458 ◽  
Author(s):  
N Tranquille ◽  
J J Emeis
Keyword(s):  
Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Time Course ◽  
Platelet Activating Factor ◽  
Calcium Ionophore ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryIn perfused rat hindlegs, platelet-activating factor and bradyki-nin induced the acute release of both tissue-type plasminogen activator (t-PA) and von Willebrand Factor (vWF). The time course of release was similar for both proteins, and the amounts of t-PA and vWF released under various conditions were closely correlated. Release of both t-PA and vWF required extracellular calcium, and could be induced by the calcium ionophore A-23187. Protein synthesis was not required for release to occur.Phorbol myristate acetate also induced release of t-PA and vWF, though with a different time course; DDAVP was inactive.The results suggest that the release of t-PA, and that of vWF, are closely linked at the cellular level.

The Role of Cyclic Nucleotides in the Release of Tissue-Type Plasminogen Activator and von Willebrand Factor

1993 ◽  
Vol 69 (03) ◽  
pp. 259-261 ◽  
Author(s):  
N Tranquille ◽  
J J Emeis
Keyword(s):  
Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Cyclic Nucleotides ◽  
Atrial Natriuretic Factor ◽  
Platelet Activating Factor ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe 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. Platelet-activating factor (PAF; 5 nM) or bradykinin (0.8 (μM) were used to induce release of t-PA and vWF.The guanylate cyclase activators sodium nitroprusside and atrial natriuretic factor reduced the induced release of t-PA and vWF. Release was not affected by inhibiting nitric oxide production with NG-nitro-L-arginine. The effects of nitroprusside and atrial natriuretic factor could not be reproduced by infusion of 8-bromo-cGMP.The adenylate cyclase activator forskolin had no effect on bradykinin-induced release of t-PA and vWF, reduced PAF-induced t-PA release, but potentiated PAF-induced vWF release. These modulatory effects were only partially mimicked by infusion of 8-bromo-cAMP.None of the compounds tested was able to induce the release of t-PA or of vWF in the absence of stimulation by bradykinin or platelet-activating factor. Cyclic nucleotides can thus modulate, but not induce, the acute release of t-PA and vWF from perfused rat hindlegs.

scholarly journals Butyrate stimulates tissue-type plasminogen-activator synthesis in cultured human endothelial cells

1987 ◽  
Vol 247 (3) ◽  
pp. 605-612 ◽  
Author(s):  
T Kooistra ◽  
J van den Berg ◽  
A Töns ◽  
G Platenburg ◽  
D C Rijken ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cyclic Amp ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Mrna Levels ◽  
Dibutyryl Cyclic Amp ◽  
Human Endothelial Cells ◽  
Tissue Type Plasminogen Activator ◽  
Cell Extracts ◽  
Type Plasminogen Activator

Incubation of cultured human endothelial cells with 5 mM-dibutyryl cyclic AMP led to an approx. 2-fold increase in tissue-type plasminogen-activator (t-PA) production over a 24 h incubation period. The stimulating effect of dibutyryl cyclic AMP could be explained by the slow liberation of butyrate, as the effect could be reproduced by addition of free butyrate to the medium, but not by addition of 8-bromo cyclic AMP or forskolin, agents known to raise intracellular cyclic AMP levels. With butyrate, an accelerated accumulation of t-PA antigen in the conditioned medium (CM) was observed after a lag period of about 6 h. Increasing amounts of butyrate caused an increasingly stimulatory effect, reaching a plateau at 5 mM-butyrate. The relative enhancement of t-PA production in the presence of 5 mM-butyrate varied among different endothelial cell cultures from 6- to 25-fold in 24 h CM. Such an increase in t-PA production was observed with both arterial and venous endothelial cells. The butyrate-induced increases in t-PA production were accompanied by increased t-PA mRNA levels. Analysis of radiolabelled CM and cell extracts by SDS/polyacrylamide-gel electrophoresis indicated that the potent action of butyrate is probably restricted to a small number of proteins. The accumulation of plasminogen activator inhibitor type 1 (PAI-1) in CM from butyrate-treated cells varied only moderately. In our study of the relationship between structure and stimulatory activity, we found that a straight-chain C4 monocarboxylate structure with a methyl group at one end and a carboxy moiety at the other seems to be required for the optimal induction of t-PA in cultured endothelial cells.

Sign in / Sign up

Export Citation Format

Share Document