Die Immunhistochemische Bestimmung von Urokinase Plasminogen Aktivator (uPA) und Plasminogen Aktivator Inhibitor-1 (PAI-1) in Kombination mit einer semiquantitativen Bildanalytik stellt eine aussagekräftige Alternativmethode zum quantitativen ELISA-Test bei Brustkrebspatientinnen dar

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.

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Relationship of Plasminogen Activator Inhibitor-1 Levels following Thrombolytic Therapy with rt-PA as Compared to Streptokinase and Patency of Infarct Related Coronary Artery

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614637 ◽

1999 ◽

Vol 82 (07) ◽

pp. 104-108 ◽

Cited By ~ 13

Author(s):

Franck Paganelli ◽

Marie Christine Alessi ◽

Pierre Morange ◽

Jean Michel Maixent ◽

Samuel Lévy ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Thrombolytic Therapy ◽

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Control Group ◽

Plasminogen Activator Inhibitor 1 ◽

Vessel Patency ◽

Activator Inhibitor ◽

Pai 1

Summary Background: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries. Methods and Results: Fifty five consecutive patients with acute MI were randomized to strep-tokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5 ± 1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p <0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p <0.002, p <0.04 and p <0.05 respectively).The same tendency was observed in the t-PA group without reaching significance. Conclusions: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.

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Automated Latex Agglutination and ELISA Testing Yield Equivalent D-Dimer Results in Patients with Recent Myocardial Infarction

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614846 ◽

1999 ◽

Vol 82 (11) ◽

pp. 1412-1416 ◽

Cited By ~ 5

Author(s):

Wojciech Zareba ◽

John Horan ◽

Arthur Moss ◽

Joel Kanouse ◽

◽

...

Keyword(s):

Myocardial Infarction ◽

Elisa Test ◽

Mean Value ◽

Latex Agglutination ◽

Test Results ◽

Coronary Death ◽

Elisa Testing ◽

Strong Linear Correlation ◽

Highly Correlated ◽

D Dimer

SummaryOur previous prospective study of post-infarction patients described a strong and significant association of increased plasma D-dimer concentrations in those who experienced a subsequent coronary death or non-fatal myocardial infarction. In the present study, we compare results on stored plasma obtained two months after the index myocardial infarction from 1,038 patients of this trial, using a simple automated latex agglutination (LA) assay in parallel with the standard ELISA test. Results show a somewhat higher mean value for the LA assay (702 ± 1092 vs. 638 ± 986 ng/ml, p = 0.0002), a strong linear correlation of the two assays (r = 0.86) and 88% agreement for values below 500 ng/ml by the ELISA test. D-dimer concentrations determined by each assay were highly correlated in patients with subsequent coronary artery events (p = 0.93) and quartile values for both the LA and ELISA were equally predictive of such events (p = 0.003 and p = 0.001, respectively). This is the first demonstration that a latex agglutination assay for D-dimer can be used to assess the prognostic risk of recurrent coronary thrombotic disease after myocardial infarction

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Genexpressionsmuster von fibrinolytischen Faktoren des Urokinase-Plasmin-Systems bei Dermatoliposklerose

Phlebologie ◽

10.1055/s-0037-1617317 ◽

1999 ◽

Vol 28 (01) ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Ch. Stetter ◽

E. Schöpf ◽

J. Norgauer ◽

W. Vanscheidt ◽

Y. Herouy

Keyword(s):

Mrna Expression ◽

De Novo ◽

Ulcus Cruris ◽

Ulcus Cruris Venosum ◽

Rt Pcr ◽

Fand Sich ◽

Pai 1

ZusammenfassungDie Dermatoliposklerose (DLS) entwickelt sich als Folge einer progredienten primären Varikosis oder eines postthrombotischen Syndroms (PTS). Trotz bestehender Hinweise auf eine veränderte intravasale fibrinolytische Aktivität bei der chronisch-venösen Insuffizienz (CVI), wurden bisher fibrinolytische Faktoren im perivaskulären Gewebe nicht untersucht. Kürzlich zeigten wir, daß bei Dermatoliposklerose Matrix-Metalloproteinasen exprimiert und aktiviert werden. Da spezifische fibrinolytische Faktoren wichtige Haupteffektoren der Matrix-Metalloproteinasenaktivierung sind, untersuchten wir kürzlich die Genexpression der Plasminogenaktivatoren vom Urokinasetyp (uPA) und vom Gewebetyp (tPA), des Urokinase-Rezeptor (uPA-R) sowie der Plasminogenaktivator-Inhibitoren (PAI-1 und PAI-2) in Gewebsbiopsien von Patienten mit Dermatoliposklerose. Zum Nachweis verwandten wir dabei die Technik der reversen Transkription und Polymerase-Kettenreaktion (RT-PCR). Es fand sich in allen Hautproben (n = 21) eine signifikant erhöhte mRNA-Expression von uPA und uPA-R im Vergleich zu gesunder Haut (n = 12). Dagegen konnte kein signifikanter Unterschied für mRNA-Transkripte von tPA, PAI-1 und PAI-2 nachgewiesen werden. Die Dermatoliposklerose zeichnet sich somit durch erhöhte transkriptionelle Expression von uPA und uPA-R aus. Eine gesteigerte De-novo-Synthese von uPA und uPA-R könnte daher bei der Aktivierung von Matrix-Metalloproteinasen und entsprechend in der Pathogenese des Ulcus cruris venosum eine zentrale Rolle spielen.

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Natriuretic Peptides Regulate the Expression of Tissue Factor and PAI-1 in Endothelial Cells

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614861 ◽

1999 ◽

Vol 82 (11) ◽

pp. 1497-1503 ◽

Cited By ~ 20

Author(s):

Hajime Tsuji ◽

Hiromi Nishimura ◽

Haruchika Masuda ◽

Yasushi Kunieda ◽

Hidehiko Kawano ◽

...

Keyword(s):

Endothelial Cells ◽

Tissue Factor ◽

Plasminogen Activator ◽

Natriuretic Peptide ◽

Culture Media ◽

Tissue Type ◽

Dependent Manner ◽

Ang Ii ◽

Plasminogen Activator Inhibitor 1 ◽

Pai 1

SummaryIn the present study, we demonstrate that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) interact with angiotensin II (Ang II) in regulative blood coagulation and fibrinolysis by suppressing the expressions of both tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by Ang II. The expressions of TF and PAI-1 mRNA were analyzed by northern blotting methods, and the activities of TF on the surface of rat aortic endothelial cells (RAECs) and PAI-1 in the culture media were respectively measured by chromogenic assay.Both BNP and CNP suppressed the expressions of TF and PAI-1 mRNA induced by Ang II in a time- and concentration-dependent manner via cGMP cascade, which suppressions were accompanied by respective decrease in activities of TF and PAI-1. However, neither the expression of tissue factor pathway inhibitor (TFPI) nor tissue-type plasminogen activator (TPA) mRNA was affected by the treatment of BNP and CNP.

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Factors Involved In the Plasminogen Activation System in Human Breast Tumours

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642505 ◽

1994 ◽

Vol 71 (05) ◽

pp. 684-691 ◽

Cited By ~ 9

Author(s):

László Damjanovich ◽

Csaba Turzó ◽

Róza Ádány

Keyword(s):

Epithelial Cells ◽

Connective Tissue ◽

Plasminogen Activators ◽

Breast Tumour ◽

Plasminogen Activation ◽

Malignant Tumours ◽

Plasminogen Activation System ◽

Activation System ◽

Malignant Breast ◽

Pai 1

SummaryThe plasminogen activation system is a delicately balanced assembly of enzymes which seems to have primary influence on tumour progression. The conversion of plasminogen into serine protease plasmin with fibrinolytic activity depends on the actual balance between plasminogen activators (urokinase type; u-PA and tissue type; t-PA) and their inhibitors (type 1 and 2 plasminogen activator inhibitors; PAI-1 and PAI-2). The purpose of this study was to determine the exact histological localization of all the major factors involved in plasminogen activation, and activation inhibition (plasmin system) in benign and malignant breast tumour samples. Our results show that factors of the plasmin system are present both in benign and malignant tumours. Cancer cells strongly labelled for both u-PA and t-PA, but epithelial cells of fibroadenoma samples were also stained for plasminogen activators at least as intensively as tumour cells in cancerous tissues. In fibroadenomas, all the epithelial cells were labelled for PAM. Staining became sporadic in malignant tumours, cells located at the periphery of tumour cell clusters regularly did not show reaction for PAI-1. In the benign tumour samples the perialveolar connective tissue stroma contained a lot of PAI-1 positive cells, showing characteristics of fibroblasts; but their number was strongly decreased in the stroma of malignant tumours. These findings indicate that the higher level of u-PA antigen, detected in malignant breast tumour samples by biochemical techniques, does not necessarily indicate increased u-PA production by tumour cells but it might be owing to the increased number of cells producing u-PA as well. In malignant tumours PAI-1 seems to be decreased in the frontage of malignant cell invasion; i.e. malignant cells at the host/tumour interface do not express PAI-1 in morphologically detectable quantity and in the peritumoural connective tissue the number of fibroblasts containing PAI-1 is also decreased.

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