scholarly journals Enhanced in Vitro Proliferation of Aortic Endothelial Cells from Plasminogen Activator Inhibitor-1-deficient Mice

2003 ◽  
Vol 279 (7) ◽  
pp. 6143-6151 ◽  
Author(s):  
Victoria A. Ploplis ◽  
Rashna Balsara ◽  
Mayra J. Sandoval-Cooper ◽  
Zhi Jun Yin ◽  
Jennifer Batten ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
In Vitro Proliferation ◽  
Aortic Endothelial Cells ◽  
Deficient Mice ◽  
Activator Inhibitor ◽  
Aortic Endothelial

Abstract T P75: Temporal Profiles of Plasminogen Activator Inhibitor-1 Concentration and Activity Changes in Circulation after Focal Stroke and Tissue Type Plasminogen Activator Administration in Rats

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Qi Liu ◽  
Xiang Fan ◽  
Helen Brogren ◽  
Ming-Ming Ning ◽  
Eng H Lo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Temporal Profiles ◽  
Activator Inhibitor ◽  
Pai 1

Aims: Plasminogen activator inhibitor-1 (PAI-1) is the main and potent endogenous tissue-type plasminogen activator (tPA) inhibitor, but an important question on whether PAI-1 in blood stream responds and interferes with the exogenously administered tPA remains unexplored. We for the first time investigated temporal profiles of PAI-1 concentration and activity in circulation after stroke and tPA administration in rats. Methods: Permanent MCAO focal stroke of rats were treated with saline or 10mg/kg tPA at 3 hours after stroke (n=10 per group). Plasma (platelet free) PAI-1 antigen and activity levels were measured by ELISA at before stroke, 3, 4.5 (1.5 hours after saline or tPA treatments) and 24 hours after stroke. Since vascular endothelial cells and platelets are two major cellular sources for PAI-1 in circulation, we measured releases of PAI-1 from cultured endothelial cells and isolated platelets after direct tPA (4 μg/ml) exposures for 60 min in vitro by ELISA (n=4 per group). Results: At 3 hours after stroke, both plasma PAI-1 antigen and activity were significantly increased (3.09±0.67, and 3.42±0.57 fold of before stroke baseline, respectively, all data are expressed as mean±SE). At 4.5 hours after stroke, intravenous tPA administration significantly further elevated PAI-1 antigen levels (5.26±1.24), while as expected that tPA neutralized most elevated PAI-1 activity (0.33±0.05). At 24 hours after stroke, PAI-1 antigen levels returned to the before baseline level, however, there was a significantly higher PAI-1 activity (2.51±0.53) in tPA treated rats. In vitro tPA exposures significantly increased PAI-1 releases into culture medium in cultured endothelial cells (1.65±0.08) and platelets (2.02±0.17). Conclution: Our experimental results suggest that tPA administration may further elevate stroke-increased blood PAI-1 concentration, but also increase PAI-1 activity at late 24 hours after stroke. The increased PAI-1 releases after tPA exposures in vitro suggest tPA may directly stimulate PAI-1 secretions from vascular walls and circulation platelets, which partially contributes to the PAI-1 elevation observed in focal stroke rats. The underlying regulation mechanisms and pathological consequence need further investigation.

scholarly journals Plasminogen activator inhibitor-1 secretion of endothelial cells increases fibrinolytic resistance of an in vitro fibrin clot: evidence for a key role of endothelial cells in thrombolytic resistance

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4204-4213 ◽  
Author(s):  
S Handt ◽  
WG Jerome ◽  
L Tietze ◽  
RR Hantgan
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Time Dependent ◽  
Plasminogen Activator Inhibitor 1 ◽  
Necrosis Factor Alpha ◽  
Activator Inhibitor ◽  
Pai 1

Time-dependent thrombolytic resistance is a critical problem in thrombolytic therapy for acute myocardial infarction. Platelets have been regarded as the main source of plasminogen activator inhibitor-1 (PAI-1) found in occlusive platelet-rich clots. However, endothelial cells are also known to influence the fibrinolytic capacity of blood vessels, but their ability to actively mediate time-dependent thrombolytic resistance has not been fully established. We will show that, in vitro, tumor necrosis factor-alpha-stimulated endothelial cells secrete large amounts of PAI-1 over a period of hours, which then binds to fibrin and protects the clot from tissue plasminogen activator- induced fibrinolysis. In vivo, endothelial cells covering atherosclerotic plaques are influenced by cytokines synthesized by plaque cells. Therefore, we propose that continuous activation of endothelial cells in atherosclerotic blood vessels, followed by elevated PAI-1 secretion and storage of active PAI-1 in the fibrin matrix, leads to clot stabilization. This scenario makes endothelial cells a major factor in time-dependent thrombolytic resistance.

Atrial Natriuretic Peptide Inhibits the Expression of Tissue Factor and Plasminogen Activator Inhibitor 1 Induced by Angiotensin II in Cultured Rat Aortic Endothelial Cells

1998 ◽  
Vol 79 (03) ◽  
pp. 631-634 ◽  
Author(s):  
Hajime Tsuji ◽  
Hiromi Nishimura ◽  
Teruhisa Kasahara ◽  
Tatsuya Sugano ◽  
Haruchika Masuda ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Atrial Natriuretic Peptide ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Ang Ii ◽  
Plasminogen Activator Inhibitor 1 ◽  
Aortic Endothelial Cells ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe pharmacological characteristics of atrial natriuretic peptide (ANP), such as natriuresis, vasodilation, or suppression of smooth muscle cell proliferation, are well investigated. However, this is the first study to report its role on blood coagulation and fibrinolysis mediated by vascular endothelial cells. In this study, the effects of ANP on the enhanced expression of tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) by angiotensin II (Ang II) in cultured rat aortic endothelial cells (RAECs) were examined. The expressions of TF and PAI-1 mRNA were detected by northern blotting methods. The activities of TF on the surface of RAECs and PAI-1 in the culture media were measured by chromogenic assay. ANP suppressed mRNA expressions of TF and PAI-1 induced by Ang II in a concentration-dependent manner. This suppression was accompanied by the decreased activities of TF and PAI-1.

Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells

Blood ◽  
2001 ◽  
Vol 97 (6) ◽  
pp. 1697-1702 ◽  
Author(s):  
Hidehiko Kawano ◽  
Hajime Tsuji ◽  
Hiromi Nishimura ◽  
Shinzo Kimura ◽  
Shingo Yano ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Receptor Antagonist ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Aortic Endothelial Cells ◽  
Activator Inhibitor ◽  
Pai 1

Serotonin (5-hydroxytryptamine, or 5-HT), released from activated platelets, not only accelerates aggregation of platelets but also is known to promote mitosis, migration, and contraction of vascular smooth muscle cells (VSMCs). These effects are considered to contribute to thrombus formation and atherosclerosis. The aim of this study was to investigate the effects of 5-HT on the expressions of coagulative and fibrinolytic factors in rat aortic endothelial cells. Endothelial cells were stimulated with various concentrations of 5-HT (0.1∼10 μM), and the expressions of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator (TPA) messenger RNAs (mRNAs) were evaluated by Northern blot analysis. The activities of TF and PAI-1 were also measured. TF and PAI-1 mRNA were increased significantly in a concentration- and time-dependent manner. However, TFPI and TPA mRNA expression did not change. The inductions of TF and PAI-1 mRNAs were inhibited by a 5-HT1/5-HT2 receptor antagonist (methiothepin) and a selective 5-HT2A receptor antagonist (MCI-9042). These results indicate that 5-HT increases procoagulant activity and reduces fibrinolytic activities of endothelial cells through the 5-HT2A receptor. It was concluded that the modulation of procoagulant and hypofibrinolytic activities of endothelial cells by 5-HT synergistically promotes thrombus formation at the site of vessel injury with the platelet aggregation, VSMC contraction, and VSMC proliferation.

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