scholarly journals Valproic acid selectively increases vascular endothelial tissue-type plasminogen activator production and reduces thrombus formation in the mouse

2016 ◽  
Vol 14 (12) ◽  
pp. 2496-2508 ◽  
Author(s):  
P. Larsson ◽  
I. Alwis ◽  
B. Niego ◽  
M. Sashindranath ◽  
P. Fogelstrand ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Tissue Type ◽  
Vascular Endothelial ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Endothelial Tissue

scholarly journals Inhibition of factor XIIIa in a canine model of coronary thrombosis: effect on reperfusion and acute reocclusion after recombinant tissue- type plasminogen activator

Blood ◽  
1990 ◽  
Vol 75 (7) ◽  
pp. 1455-1459 ◽  
Author(s):  
RJ Shebuski ◽  
GR Sitko ◽  
DA Claremon ◽  
JJ Baldwin ◽  
DC Remy ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Coronary Thrombosis ◽  
Tissue Type ◽  
Factor Xiiia ◽  
Specific Factor ◽  
Crosslinking Reaction ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Residual Thrombus

Abstract The effect of inhibition of factor XIIIa with 2-(l-acetonylthio)-5- methylthiazolo[2,3-b]1,3,4-thiadiazo lium perchlorate (L-722,151) on coronary thrombolysis and reocclusion was studied in an acute dog model of electrically induced coronary thrombosis. L-722,151 (0.1 mg/kg/min intravenously [IV] or placebo was administered 15 minutes before current initiation (150 microA) and for the duration of the experiment (270 minutes). Fifteen minutes after thrombus formation, heparin (300 U/kg, IV) was administered, followed 45 minutes later by recombinant tissue-type plasminogen activator (tPA) (10 micrograms/kg/min, IV for 90 minutes). Placebo-treated animals thrombosed at 48.9 +/- 8.1 minutes (mean +/- SEM) and reperfused in response to tPA at 49.1 +/- 9.3 minutes. L-722,151 pretreated animals thrombosed at 44.4 +/- 9.7 minutes and reperfused in response to tPA at 16.4 +/- 2.8 minutes (P less than .05 v vehicle). Furthermore, residual thrombus mass was reduced by L-722,151 from 6.9 +/- 1.9 mg in placebo-treated animals to 1.7 +/- 0.6 mg (P less than .05 v vehicle). Acute reocclusion occurred in 86% of placebo and in 75% of L-722,151-treated animals. The incidence of tPA-induced reperfusion in L-722,151-treated dogs was 100% (8 of 8), whereas only 70% (7 of 10) of placebo-treated dogs reperfused. These results demonstrate that pretreatment with L-722,151 hastens reperfusion time threefold and reduces residual thrombus mass. These effects occurred with no change in systemic blood pressure in response to L-722,151. When L-722,151 was administered 15 minutes after thrombus formation in a separate group of dogs (n = 5), no beneficial effect on thrombolysis time or thrombus mass was observed. Thus, the specific factor XIIIa catalyzed crosslinking reaction(s), which may determine(s) resistance to plasmin-mediated fibrin degradation, occur(s) rapidly. Inhibition of this crosslinking by pretreatment with L-722,151 promotes tPA-induced thrombolysis.

scholarly journals Arsenite Inhibits Tissue-Type Plasminogen Activator Synthesis through NRF2 Activation in Cultured Human Vascular Endothelial EA.hy926 Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 739
Author(s):  
Tsuyoshi Nakano ◽  
Tsutomu Takahashi ◽  
Chika Yamamoto ◽  
Eiko Yoshida ◽  
Toshiyuki Kaji ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Vascular Endothelial Cells ◽  
Tissue Type ◽  
Vascular Endothelial ◽  
Tissue Type Plasminogen Activator ◽  
Nrf2 Pathway ◽  
Type Plasminogen Activator ◽  
Ea.Hy926 Cells ◽  
Pai 1

Chronic arsenic exposure is known to be related to the progression of atherosclerosis. However, the pathogenic mechanisms of arsenic-induced atherosclerosis have not been fully elucidated. Because disruption of the blood coagulation/fibrinolytic system is involved in the development of arteriosclerosis, we investigated the effect of arsenite on fibrinolytic activity in human vascular endothelial EA.hy926 cells in the present study. Fibrinolysis depends on the balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) secreted from vascular endothelial cells. We found that arsenite reduced fibrinolytic t-PA activity by inhibiting its synthesis without affecting PAI-1 production. The inhibitory effect of arsenite on t-PA expression was partially recovered by the reactive oxygen species (ROS) scavenger Trolox. The nuclear factor erythroid 2 related factor 2 (NRF2) pathway is known to be activated by arsenite via ROS production. We confirmed that arsenite activated the NRF2 pathway, and arsenite-induced inhibition of fibrinolytic t-PA activity was abrogated in NRF2-knockdown EA.hy926 cells. These results suggest that arsenite inhibits the fibrinolytic activity of t-PA by selectively suppressing its synthesis via activation of the NRF2 pathway in vascular endothelial cells.

scholarly journals Endothelial Tissue-Type Plasminogen Activator Release in Coronary Heart Disease

1998 ◽  
Vol 31 (3) ◽  
pp. 547-551 ◽  
Author(s):  
Hans Martin Hoffmeister ◽  
Michael Jur ◽  
Monika Ruf-Lehmann ◽  
Uwe Helber ◽  
Wolfgang Heller ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Endothelial Tissue

Effects of IL-1β and IL-6 on tissue-type plasminogen activator expression in vascular endothelial cells

2008 ◽  
Vol 123 (2) ◽  
pp. 342-351 ◽  
Author(s):  
Pia Larsson ◽  
Erik Ulfhammer ◽  
Lena Karlsson ◽  
Maria Bokarewa ◽  
Karin Wåhlander ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Vascular Endothelial Cells ◽  
Tissue Type ◽  
Vascular Endothelial ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator
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