A New Hypothesis: Possible Mechanisms in the Involvement of the Increased Plasminogen Activator Activity in Branching Regions of the Aorta in the Initiation of Atherosclerosis

1980 ◽  
Vol 43 (02) ◽  
pp. 141-146 ◽  
Author(s):  
A Smokovitis
Keyword(s):  
Plasminogen Activator ◽  
Early Life ◽  
Fibrinolytic Activity ◽  
Atherosclerotic Lesion ◽  
Protective Role ◽  
Fibrinolytic System ◽  
Actual Role ◽  
Plasminogen Activator Activity ◽  
New Hypothesis

SummaryBranching regions of the aorta are predilection regions for atherosclerosis. The intima in the branching regions of the normal aorta shows a constantly increased plasminogen activator activity from early life. At these areas, the endothelium is also damaged, it shows increased permeability, etc. The constantly increased plasminogen activator activity (local plasmin production) might play a protective role or on the contrary might participate in the initiation of atherosclerosis at the branching regions through a number of proved or suggested mechanisms.No matter what the actual role of the locally increased plasminogen activator activity in the initiation of atherosclerosis is, the role of the fibrinolytic system in the progression of the atherosclerotic lesion seems to be clear. There is an accumulation of evidence that the impaired fibrinolytic activity in atherosclerotics participates in the progression and the complications of the disease.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Tissue Plasminogen Activator in Human Megakaryocytes and Platelets: Immunocytochemical Localization, Immunoblotting and Zymographic Analysis

1988 ◽  
Vol 59 (03) ◽  
pp. 529-534 ◽  
Author(s):  
C Jeanneau ◽  
Y Sultan
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Blood Platelets ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Sds Page ◽  
Tissue Plasminogen ◽  
Zymographic Analysis

SummaryTwo approaches were used to identify and characterize the presence of tissue plasminogen activator (t-PA) in megakaryocytes and platelets. We investigated the fibrinolytic activity of human megakaryocytes (MK) and platelets. The presence of t-PA antigen in megakaryocytes and platelets was demonstrated using immunocytochemical techniques and polyclonal or monoclonal antibodies specific for t-PA. When cells were applied to fibrin plates, lysis zones developed around isolated human megakaryocytes, whereas no fibrinolytic activity appeared when either intact washed platelets or platelet lysate were deposited. After SDS-PAGE of platelet and MK extracts (Triton X-100) immunoblotting and peroxidase staining identified t-PA antigen in several bands. Zymographic analysis of SDS-PAGE carried out on fibrin film overlays identified one or two zones corresponding to free or complexed t-PA. These results indicate that t-PA is present in platelets as well as in the precursor cells, however, in platelets, t-PA may not be immediately available for plasminogen activation and fibrin degradation. From our findings and from previous work of others, it appears that platelets may either activate or inhibit the fibrinolytic system. Therefore the conditions of plasminogen activation by platelet t-PA and plasmin inhibition by platelet α2-antiplasmin or other inhibitors have to be precised before the role of platelets in clot dissolution is understood.The physiological role of platelets in fibrinolysis and clot dissolution remains unclear. In 1953, the antifibrinolytic activity of blood platelets was demonstrated (1) and in the early 1960’s a fibrinolytic activity, increasing with platelet concentration in the experimental system, was shown (2, 3). In 1979, it was demonstrated that metabolically active platelets were necessary for platelets to play a role in the fibrinolytic system (4). More recently it was established by Plow and Collen (5) that the specific plasmin inhibitor, α2-antiplasmin is a constituent of platelet α-granules.In the present study, we investigated the fibrinolytic components and activity of human megakaryocytes and platelets, using zymographic and immunochemical techniques. We report here our observations that human megakaryocytes and platelets contain tissue plasminogen (t-PA) which possesses fibrinolytic activity.

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Endothelial Injury ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Wild Type ◽  
Type Plasminogen Activator ◽  
Pai 1

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.

On the Fibrinolytic System in Aged Rats, and Its Reactivity to Endotoxin and Cytokines

1992 ◽  
Vol 67 (06) ◽  
pp. 697-701 ◽  
Author(s):  
J J Emeis ◽  
A Brouwer ◽  
R J Barelds ◽  
M A Horan ◽  
S K Durham ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
High Dose ◽  
Base Line ◽  
Aged Rats ◽  
Tissue Type Plasminogen Activator ◽  
Young Rats ◽  
Type Plasminogen Activator

SummaryAged rats are more susceptible to endotoxin-induced effects, including microthrombosis and platelet aggregation, than are young rats. To investigate whether changes in the fibrinolytic system might be involved, we investigated the fibrinolytic activity in plasma euglobulin fractions and tissues (lung and heart) of young (6-months old) and aged (24-months old) rats under baseline conditions and after challenge with endotoxin. Aged rats had lower plasma levels of tissue-type plasminogen activator (t-PA) and of urokinase-type PA (u-PA) activity. PA inhibitor (PAI) activity was higher in the plasma of aged rats, as was t-PA activity in lung and heart.Rats were treated with either a low dose (1 μg/kg) or a high dose (10 mg/kg) of endotoxin. Both treatments induced a transient phase of increased blood fibrinolytic activity, as evidenced by higher levels of tissue-type plasminogen activator (t-PA) activity and decreased levels of PA inhibitor (PAI) activity. Over time, the fibrinolytic activity decreased, probably due to increased levels of PA inhibitor.Both the early increase in t-PA activity, and the subsequent increase in PAI activity, were more pronounced in the aged rats, as compared with the younger rats, after the high dose of endotoxin. The aged rats also responded to an injection of interleukin-1β or tumor necrosis factor-α with a larger increase of PAI activity than did the younger rats.Together the data suggest that, compared to young rats, aged rats have a decreased base-line plasma fibrinolytic activity, while their fibrinolytic system is more responsive to challenge by endotoxin and cytokines.

Effect of Bentonite on Fibrinolytic System in Serum

1963 ◽  
Vol 10 (01) ◽  
pp. 120-132 ◽  
Author(s):  
E. S Olesen
Keyword(s):  
Guinea Pig ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
High Potential ◽  
Fibrinolytic System ◽  
Fibrinolytic Agents ◽  
Isoelectric Precipitation ◽  
Active Protease ◽  
Pig Serum

SummaryTreatment of serum with bentonite led to a reduced content of inhibitors of trypsin and urokinase in the isoelectrically precipitated euglobulin, and removed fibrinolytic agents and precursors from serum. Bentonite-treated serum added to untreated serum reduced precipitation of the above inhibitors, and presumably also precipitation of inhibitors against a plasminogen activator of serum.Bentonite-treated serum (whether from pig, ox, guinea-pig, or man), added to untreated guinea-pig serum, produced fibrinolytic activity on isoelectric precipitation of the mixture; the activity of the euglobulin was due to an activator of plasminogen as well as an active protease, probably plasmin. The described effects of bentonite-treated serum are similar to those previously reported for anionic polyelectrolytes. Possible mechanisms are discussed.The “non-specific” activation of fibrinolytic activity by means of bentonite emphasizes that guinea-pig serum [which is characterized by a high potential for “nonspecific” activation of its fibrinolytic system Olesen (1962)] contains all the elements required for the formation of an activator of plasminogen, and thus the activation of its plasminogen to plasmin.

Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: The role of the anhepatic period

Hepatology ◽  
1992 ◽  
Vol 16 (2) ◽  
pp. 404-408 ◽  
Author(s):  
C. Minke Bakker ◽  
Herold J. Metselaar ◽  
Theo N. Groenland ◽  
Maria J. Gomes ◽  
Eduard A. R. Knot ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Type Plasminogen Activator ◽  
Anhepatic Period

scholarly journals The Lysis of Early Fibrin by Eosinophils

1977 ◽  
Author(s):  
Hau C. Kwaan ◽  
Ali A. Hatem
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Cell Membranes ◽  
Red Cell ◽  
Platelet Thrombus ◽  
Platelet Aggregates ◽  
Platelet Thrombi ◽  
Arteries And Veins ◽  
Morphologic Changes

This study examins the role of leukocytes within a thrombus by demonstrating the morphologic detail of their activities, the chemotactic properties of thrombi and the presence of plasminogen and possible plasminogen activator within eosinophils. A model which produces discrete, reproducible platelet thrombi in arteries and veins of dogs allowed timed studies of their early evolution. In this model, the growth of the thrombus was constantly monitored by a flowmeter and the thrombus could thus be removed at a selected period in its formation. It was then studied histologically for fibrin activity and also ultrastructually. Little fibrinolytic activity was found. In contrast to neutrophils which are concerned particularly with the phagocytosis and disruption of platelet aggregates, we observed that eosinophils participate in the lysis and disruption of the fibrin within these aggregates. The fibrin is rarely phagocytosed but is acted on at the surfaces of the eosinophils, usually in shallow invaginations of the cell membranes. The fibrin shows morphologic changes of lysis. It appears that eosinophils and neutrophils are concerned with the transformation of the early fibrin and platelet thrombus, rather than with the resolution of the formed, mainly fibrin and red cell thrombus.

The Effect of Exocrine Pancreas Stimulation on the Coagulation and Fibrinolytic System in Dogs

1973 ◽  
Vol 29 (03) ◽  
pp. 603-609
Author(s):  
A Gabryelewicz ◽  
J Prokopowicz ◽  
W Szalaj ◽  
N Wolosowicz ◽  
W Laszewicz ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Prothrombin Time ◽  
Fibrinolytic Activity ◽  
Exocrine Pancreas ◽  
Blood Platelet ◽  
Fibrinolytic System

SummaryThe coagulation and fibrinolytic systems have been investigated in the dogs treated intravenously with secretin, pancreozymin and CCK.There was significant shortening of plastic and glass clotting times, a fall in blood platelet numbers, prolongation of the prothrombin time, and a transitory inhibition of plasma euglobulin fibrinolytic activity. The greatest changes were found after CCK.It should be stressed that the peak changes were earlier and more intense when morphine was given with the hormones.In the authors’ opinion the present findings support the supposition concerning the role of enzymatic toxemia in hemostatic disturbances seen in acute pancreatitis.

Fibrinolytic Activity in Rat Anaphylaxis

1974 ◽  
Vol 32 (02/03) ◽  
pp. 341-349 ◽  
Author(s):  
László Fésüs ◽  
Éva Ölveti ◽  
Béla Csaba ◽  
László Muszbek
Keyword(s):  
Plasminogen Activator ◽  
Pertussis Vaccine ◽  
Bordetella Pertussis ◽  
Anaphylactic Shock ◽  
Fibrinolytic Activity ◽  
Fibrinolytic System ◽  
Plasma Fibrinogen ◽  
Fibrinogen Concentration

SummaryThe activity of fibrinolytic system measured by different methods and the concentration of plasma fibrinogen were determined in rats suffering mild or severe active anaphylactic shock.In severe anaphylactic shock of Bordetella Pertussis Vaccine pretreated animals, the plasminogen activator content was markedly enhanced and the fibrinolytic activity significantly increased; however, the total inhibitor capacity did not change. The fall in fibrinogen concentration was only moderate. Similar but minor enhancement of fibrinolysis could be observed in mild anaphylaxis.The results suggest that the activated plasminogen-plasmin system may contribute to the development of severe anaphylactic outcome in the rat. The possible pathogenic mode is discussed.

CLINICAL SYNDROMES ASSOCIATED WITH DEFICIENT FIBRINOLYTIC ACTIVITY OF THE LUNG

PEDIATRICS ◽  
1960 ◽  
Vol 25 (3) ◽  
pp. 419-431
Author(s):  
Jack Lieberman
Keyword(s):  
Enzyme Activity ◽  
Fibrinolytic Activity ◽  
Proteolytic Enzyme ◽  
Saline Solution ◽  
Lung Homogenate ◽  
Fibrocystic Disease ◽  
Enzyme Defect ◽  
Clinical Syndromes ◽  
New Hypothesis

Plasminogen-activator activity in lung was investigated in 211 controls and 8 children with fibrocystic disease of the pancreas. Twenty-seven of the 211 controls lacked enzyme activity of the whole lung homogenate, while 7 out of the 8 specimens from children with fibrocystic disease lacked activity. The defect in all 7 of the specimens from patients with fibrocystic disease was shown to be due to excessive inhibition, and the inhibitor could easily be removed by washing the lung sediment with normal saline solution. Eight of the controls showed a similar pattern of enzyme inhibition. A new hypothesis as to the pathogenesis of fibrocystic disease is proposed which postulates the existence of an abnormal protease inhibitor in both the lungs and pancreas. The manner in which such an enzyme defect could account for the manifestations of the disease, and the possible role of a proteolytic enzyme in mucoprotein synthesis are discussed.

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