Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Tissue Plasminogen Activator”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1996

Tissue plasminogen activator, tissue plasminogen activator inhibitor and lipoprotein(a) in patients with coronary, epiaortic and peripheral occlusive artery disease.

In order to evaluate the relationship between the presence of atherosclerotic disease, documented by angiography, and the fibrinolytic profile, 262 consecutive patients affected by coronary (n = 90), epiaortic (n = 60) and peripheral (n = 104) artery disease have been included in the study. Twenty-two healthy subjects were used as controls for laboratory parameters determination. All patients were classified on the basis of the presence (S+) or absence (S-) of clinically significant stenosis, according to specific scoring systems. Lipoprotein(a), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA) and the PAI-1/t-PA ratio were significantly lower in controls than in coronary, epiaortic and peripheral artery disease patients. However, the levels of these parameters were not statistically different between S+ and S- subjects. These results confirm the association between lipoprotein(a), PAI-1 and t-PA levels and the presence of atherosclerotic disease independently of the arterial districts considered, while they do not appear to be directly linked to the severity of the morphological disease.

Adult↗
PubMed1991

[Unstable angina: tissue plasminogen activator, tissue plasminogen activator inhibitors, protein C and other factors of the blood fibrinolytic system].

The authors examined the activities of plasminogen activator, its inhibitor, the levels of C protein, antithrombin III, alpha 2-antiplasmin, plasminogen, fibrinogen, fibrinogen/fibrin degradation products in 22 patients with unstable angina by using the vein occlusive test. No significant differences were found in the examined parameters while comparing the group of stable angina patients and healthy subjects. It was concluded that thrombogenesis disturbances in unstable angina were regional and the recording of peripheral blood fibrinolytic parameters failed to detect any changes characteristic of unstable angina.

Adult↗
PubMed2002

Gonadotropin surge-induced up-regulation of the plasminogen activators (tissue plasminogen activator and urokinase plasminogen activator) and the urokinase plasminogen activator receptor within bovine periovulatory follicular and luteal tissue.

This study examined the effect of the preovulatory gonadotropin surge on the temporal and spatial regulation of tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), and uPA receptor (uPAR) mRNA expression and tPA, uPA, and plasmin activity in bovine preovulatory follicles and new corpora lutea collected at approximately 0, 6, 12, 18, 24, and 48 h after a GnRH-induced gonadotropin surge. Messenger RNAs for tPA, uPA, and uPAR were increased in a temporally specific fashion within 24 h of the gonadotropin surge. Localization of tPA mRNA was primarily to the granulosal layer, whereas both uPA and uPAR mRNAs were detected in both the granulosal and thecal layers and adjacent ovarian stroma. Activity for tPA was increased in follicular fluid and the preovulatory follicle apex and base within 12 h after the gonadotropin surge. The increase in tPA activity in the follicle base was transient, whereas the increased activity in the apex was maintained through the 24 h time point. Activity for uPA increased in the follicle apex and base within 12 h of the gonadotropin surge and remained elevated. Plasmin activity in follicular fluid also increased within 12 h after the preovulatory gonadotropin surge and was greatest at 24 h. Our results indicate that mRNA expression and enzyme activity for both tPA and uPA are increased in a temporally and spatially specific manner in bovine preovulatory follicles after exposure to a gonadotropin surge. Increased plasminogen activator and plasmin activity may be a contributing factor in the mechanisms of follicular rupture in cattle.

Animals↗
PubMed1990

A depression of active tissue plasminogen activator in plasma characterizes patients with unstable angina pectoris who develop myocardial infarction.

The balance between the coagulation system generating fibrin and its subsequent removal by the fibrinolytic system determines the fate of fibrin deposited in the vascular system. In a prospective study, selected haemostatic variables assessing this balance were determined in plasma samples from 20 consecutive patients admitted with unstable angina pectoris. Over a follow-up period of 6 years, eight patients developed myocardial infarction, whereas 12 patients did not. There was no significant difference between the two groups in the median plasma concentrations of thrombin-antithrombin III complexes reflecting the coagulant activity. The infarction group was characterized by a significantly lower median activity of tissue plasminogen activator in plasma euglobulins (P less than 0.05), a higher median concentration of tissue plasminogen activator antigen in plasma (P less than 0.05) and a tendency to higher plasma levels of antigenic and functional plasminogen activator inhibition. In all patients, the activities of tissue plasminogen activator inhibitor and of tissue plasminogen activator were significantly associated (rs = -0.4811, P less than 0.05). We conclude that a depressed fibrinolytic capacity attributable to a low tissue plasminogen activator activity is of pathogenetic importance for the development of myocardial infarction in patients with unstable angina pectoris.

Aged↗
PubMed1995

The activation of type 1 and type 2 plasminogen by type I and type II tissue plasminogen activator.

Tissue plasminogen activator (tPA) was fractionated using lysine-Sepharose affinity chromatography. Type I, type II, and a minor peak with high affinity for lysine (designated type D) tPA were recovered. In an indirect amidolytic assay involving native human Glu-plasminogen and fibrin, type II tPA showed a 2-fold higher activity than type I. To explore the combinatorial effect of the variable glycosylation status of both tPA and plasminogen, kinetic constants for fibrin-dependent plasminogen activation were determined for combinations of type I, II, and D tPA with type 1 and 2 plasminogen. Within a 4-fold range, the fastest rate was achieved from the combination of type D (type II + D) tPA and type 2 plasminogen. N-Glycosylation of plasminogen increased the Km value for activation by all tPA variants; N-glycosylation of type I tPA at Asn184 decreased the kcat (turnover) values for the fibrin-dependent activation of plasminogen over type II tPA, while type D tPA showed the highest turnover rate. In the presence of fibrinogen fragments, N-glycosylation of plasminogen at site 289 modulates the kinetics of association of enzyme and substrate, while N-glycosylation at site 184 on tPA modulates the turnover rate of the enzyme.

Amino Acid Sequence↗
PubMed1990

Rebleeding in experimental traumatic hyphema treated with intraocular tissue plasminogen activator.

Tissue plasminogen activator has recently been shown to enhance the clearance of experimental nontraumatic hyphema in animals. However, hyphema in human eyes usually results from ocular trauma, and rebleeding is a serious complication. Hemorrhage is also a potential complication of fibrinolytic therapy. We assessed the incidence of rebleeding in an animal model of surgically induced traumatic hyphema after intracameral injection of tissue plasminogen activator (25 micrograms) or physiological saline. Eight eyes were each treated with tissue plasminogen activator or physiological saline at 10 minutes, 24 hours, 48 hours, or 72 hours after injury. Controls were 8 eyes with hyphema but no intracameral injection. No eyes treated with physiological saline (total, 32 eyes) or control eyes rebled. In contrast, the incidence of rebleeding from the injury site in eyes treated with tissue plasminogen activator was 88% (7/8) at 10 minutes, 75% (6/8) at 24 hours, 50% (4/8) at 48 hours, and 0% (0/8) at 72 hours after injury. Treatment of traumatic hyphema with tissue plasminogen activator prior to healing of damaged vascular endothelium may contribute to rebleeding.

Animals↗
PubMedDate not supplied

[Plasminogen activation by tissue plasminogen activator on fibrin clots with different surface structures].

Transformation of fibrinogen into fibrin with consequent formation of the fibrin clot trimeric structure is one of the final steps in the blood coagulation system. The plasminogen activation by the tissue plasminogen activator (t-PA) is one of the fibrinolysis system key reactions. The effect of different factors on transformation of plasminogen into plasmin is capable to change essentially the equilibrium between coagulation and fibrinolytic sections of haemostasis system. We have studied the plasminogen activation by tissue plasminogen activator on fibrin clots surface formed on the interface between two phases and in presence of one phase. The t-PA plasminogen activation rate on fibrin clots both with film and without it the latter has been analyzed. These data allow to assume that the changes of fibrin clot structure depend on its formations, as well as are capable to influence essentially on plasminogen activation process by means of its tissue activating agent.

Fibrin↗
PubMed1996

Membrane depolarization induces calcium-dependent secretion of tissue plasminogen activator.

Tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to active plasmin, is produced in the rat and mouse hippocampus and participates in neuronal plasticity. To help define the role of tPA in the nervous system, we have analyzed the regulation of its expression in the neuronal cell line PC12. In control cultures, tPA activity is exclusively cell-associated, and no activity is measurable in the culture medium. When the cells are treated with depolarizing agents, such as KCI, tPA activity becomes detectable in the medium. The increased secreted tPA activity is not accompanied by an increase in tPA mRNA levels, and it is not blocked by protein synthesis inhibitors. In contrast, tPA release is abolished by Ca2+ channel blockers, suggesting that chemically induced membrane depolarization stimulates the secretion of preformed enzyme. Moreover, KCI has a similar effect in vivo when administered to the murine brain via an osmotic pump: tPA activity increases along the CA2-CA3 regions and dentate gyrus of the hippocampal formation. These results demonstrate a neuronal activity-dependent secretory mechanism that can rapidly increase the amount of tPA in neuronal tissue.

Animals↗
PubMed1984

Differences between uterine and melanoma forms of tissue plasminogen activator.

Tissue plasminogen activator purified from human uterine tissue exhibits differences in N-terminal starting positions in relation to the melanoma cell plasminogen activator usually studied. A new starting position is compatible with an additional N-terminal processing apart from those already known. Like the melanoma activator, the uterine activator was found to yield protein chains starting at either of two positions. One of these was identical between uterine and melanoma activators, whereas the other was unique in each case. The most abundant starting position for the uterine preparation was at a valine residue, apparently from cleavage of a Gln-Val bond, and corresponding to Val-7 of the longest form of the melanoma activator chain.

Amino Acid Sequence↗
PubMedDate not supplied

Topical treatment of postvitrectomy fibrin formation with tissue plasminogen activator.

Tissue plasminogen activator (tPA) is able to dissolve any fibrin material that forms in the anterior chamber or vitreous humor. This property has been reported by various experimental studies performed in rabbits. The authors demonstrate the tPA eye drops administered to patients with postoperative hyphema, which did not respond to traditional therapy, gave rapid clearance of the clot. Following its topical administration for the first time in patients, the harmless nature of the drug is emphasized as well as its efficacy. This study indicates the promising features of this drug which deserve further investigation.

Administration, Topical↗
PubMed2000

Successful lysis of right and left heart thrombus by tissue plasminogen activator.

Tissue plasminogen activator (t-PA) was administered to three patients with newly developed intracardiac thrombi. Cases 1 and 2 developed right heart thrombi after radiofrequency ablation for atrioventricular nodal reentrant tachycardia and case 3 had tachycardia-related cardiomyopathy and a left ventricular thrombus. In all three patients, the intracardiac thrombi were successfully eliminated following t-PA therapy without major bleeding complications. These observations suggest that t-PA is effective in lysing new thrombus complicating radiofrequency ablation or heart failure and may be the therapy of choice in these conditions. Cathet. Cardiovasc. Intervent. 49:91-96, 2000.

Adult↗
PubMed1990

Treatment of experimental vitreous hemorrhage with tissue plasminogen activator.

Tissue plasminogen activator(tPA) is a fibrin-specific fibrinolytic agent that has recently been shown to be effective in accelerating the clearance of hyphema. Intravitreal injection of tPA can promote rapid lysis of experimental intravitreal fibrin clots. The purpose of this study was to investigate the efficacy of intravitreal tPA injection for the treatment of vitreous hemorrhage in normal phakic non-vitrectomized rabbit eyes. Vitreous hemorrhages were produced by intravitreal injections of 0.05 ml of autologous whole blood in 25 rabbit eyes with intact vitreous. The injection of 25 or 100 micrograms of tPA in 15 eyes resulted in the clearance of vitreous hemorrhage in 99 +/- 19 or 34 +/- 6.5 days, respectively. This was significantly faster than in the control eyes in which the clearance was not seen until 131 +/- 17 days later. No tractional retinal detachment was observed.

Animals↗
PubMed2004

The neurotoxicity of tissue plasminogen activator?

Tissue plasminogen activator (tPA), a fibrin specific activator for the conversion of plasminogen to plasmin, stimulates thrombolysis and rescues ischemic brain by restoring blood flow. However, emerging data suggests that under some conditions, both tPA and plasmin, which are broad spectrum protease enzymes, are potentially neurotoxic if they reach the extracellular space. Animal models suggest that in severe ischemia with injury to the blood brain barrier (BBB) there is injury attributed to the protease effects of this exogenous tPA. Besides clot lysis per se, tPA may have pleiotropic actions in the brain, including direct vasoactivity, cleaveage of the N-methyl-D-aspartate (NMDA) NR1 subunit, amplification of intracellular Ca++ conductance, and activation of other extracellular proteases from the matrix metalloproteinase (MMP) family, e.g. MMP-9. These effects may increase excitotoxicity, further damage the BBB, and worsen edema and cerebral hemorrhage. If tPA is effective and reverses ischemia promptly, the BBB remains intact and exogenous tPA remains within the vascular space. If tPA is ineffective and ischemia is prolonged, there is the risk that exogenous tPA will injure both the neurovascular unit and the brain. Methods of neuroprotection, which prevent tPA toxicity or additional mechanical means to open cerebral vessels, are now needed.

Animals↗
PubMed1989

Cell-type-specific and site-specific N-glycosylation of type I and type II human tissue plasminogen activator.

Tissue plasminogen activator (t-PA) is an important initiator of fibrinolysis. The t-PA polypeptide has four potential N-glycosylation sites of which three are occupied in type I (Asn-117, -184, and -448) and two in type II (Asn-117 and -448). In an effort to elucidate the factors controlling the expression of N-linked oligosaccharides on this polypeptide, we have used a combination of sequential exoglycosidase digestion, methylation analysis, and controlled acetolysis to determine the oligosaccharide structures at each of the N-glycosylation sites of type I and type II t-PA when isolated from a human colon fibroblast cell strain and from a Bowes melanoma cell line. Our results suggest the following: (i) type I and type II t-PA are N-glycosylated in an identical way at Asn-117 and Asn-448, when isolated from the same cell line; (ii) Asn-117 is predominantly associated with oligomannose-type structures in all cases; (iii) Asn-184 and Asn-448 are predominantly associated with complex-type structures when t-PA is isolated from fibroblast cells, but with both complex- and oligomannose-type structures when isolated from melanoma cells; (iv) fibroblast cell derived t-PA is associated with both neutral and sialylated oligosaccharides, while melanoma cell derived t-PA is also associated with sulfated oligosaccharides, which are located exclusively at Asn-448 of type II t-PA; (v) no complex-type structures occur in common between t-PA from the two cell lines. These results indicate that the t-PA glycoprotein is secreted by each cell line as a set of glycoforms, each glycoform being unique with respect to the nature and disposition of oligosaccharides on a common polypeptide. Further, the two cell lines express no glycoform in common, despite expressing the same t-PA polypeptide. The implications of these results for both the control of oligosaccharide processing in different cell lines and the genetic engineering of mammalian glycoproteins are discussed.

Amino Acids↗
PubMed1982

Studies on the kinetics of plasminogen activation by tissue plasminogen activator.

The steady-state rate of plasminogen activation by tissue plasminogen activator has been determined at various plasminogen concentrations. A plasmin substrate method similar to that presented by Christensen and Müllertz (Biochim. Biophys. Acta 480 (1977) 257-281) was used. The reaction was studied using one-chain type and two-chain type tissue plasminogen activator, N-terminal glutamic acid and N-terminal lysine plasminogen in the presence and in the absence of fibrin (eight studies). The kinetic data were fitted to a general Wong-Hanes equation and the simplest equation with significant parameters was found. In the absence of fibrin N-terminal glutamic acid plasminogen activation obeyed the Michaelis-Menten rate equation (Km 4.9 and 7.6 micro M and kcat 0.0013 and 0.0078 s-1 for one-chain type and two-chain type tissue plasminogen activator, respectively. In the absence of fibrin the activation of N-terminal lysine plasminogen activation failed to obey the Michaelis-Menten rate equation. Fibrin was found to stimulate greatly (up to 1000-fold) the steady-state activation rate. A theory for the fibrin stimulating mechanism is presented.

Animals↗
PubMed1997

Acceleration of plasminogen activation by tissue plasminogen activator on surface-bound histidine-proline-rich glycoprotein.

Histidine-proline-rich glycoprotein (HPRG), also known as histidine-rich glycoprotein, is a major plasminogen-binding protein. In this work we characterized extensively the circumstances under which HPRG accelerates plasminogen activation and the specificity of this effect. Soluble HPRG did not significantly influence plasminogen activation. In contrast, native HPRG bound to hydrazide or nickel chelate surfaces strongly stimulated the activation of plasminogen by tissue plasminogen activator, but not by urokinase or streptokinase. The efficiency of activation on surface-bound HPRG was increased for Glu-plasminogen (41-fold), Lys-plasminogen (17-fold), and cross-linked Glu-plasminogen (11-fold) but not for mini-plasminogen, and was mainly due to a decrease in the apparent Km. A reduced susceptibility to inhibition by chloride ions contributed to the higher activation rate of Glu-plasminogen on an HPRG surface. The immobilized N- and C-terminal domains, but not the histidine-proline-rich domain of HPRG, also bound plasminogen and stimulated its activation. HPRG-enhanced plasminogen activation was proportional to the quantity of HPRG immobilized and was abolished by anti-HPRG antiserum, by low concentrations of epsilon-aminocaproic acid, by methylation of lysine residues in HPRG, and by treatment of HPRG with carboxypeptidase B. Soluble HPRG and a plasminogen fragment, kringle 1-2-3, acted as competitive inhibitors by binding to plasminogen and immobilized HPRG, respectively. The interaction of the conserved C-terminal lysine of HPRG with the high affinity lysine binding site of plasminogen is necessary and sufficient to accelerate plasminogen activation. Unlike other stimulators of plasminogen activation, the effect of HPRG on fibrinolysis is modulated by factors that influence the equilibrium between solution and surface-bound HPRG.

Animals↗
PubMed1990

Effect of PAI-1 levels on the molar concentrations of active tissue plasminogen activator (t-PA) and t-PA/PAI-1 complex in plasma.

We determined the in vivo molar concentrations of active tissue plasminogen activator (t-PA), active plasminogen activator inhibitor type 1 (PAI-1), and t-PA/PAI-1 complex. t-PA activity was measured in plasma stabilized by immediate acidification. PAI-1 activity and t-PA/PAI-1 complex antigen were measured in citrated plasma; these measurements were corrected for the loss in PAI-1 activity and increase in complex that occurs in unacidified plasma samples due to the continued reaction between t-PA and PAI-1 after the sample was drawn. To convert t-PA and PAI-1 activity measurements into molar concentrations we determined the specific molar activity of t-PA and PAI-1 in vivo: 4.48 x 10(13) IU/mol. Of 72 subjects studied, 13 had less than 150 pmol/L active PAI-1; in these individuals 33% +/- 21% of their t-PA was active and the molar ratio of active t-PA to active PAI-1 was 0.20 +/- 0.13. In the 11 subjects with greater than 500 pmol/L active PAI-1, 1.5% = 1.1% of the t-PA was active and the molar ratio of active t-PA to active PAI-1 was 0.0043 +/- 0.0036. Overall, the fraction of active t-PA declined exponentially as a function of the active PAI-1 concentration. During the day, the percentage of total t-PA that was active increased from 12% at 8:00 AM to 31% at 8:00 PM, while the molar ratio of active t-PA to active PAI-1 increased from 0.05 to 0.22 from morning to evening (n = 12).

Antithrombins↗
PubMed1985

The potentiating effect of platelet on plasminogen activation by tissue plasminogen activator.

A new role for platelets in fibrinolysis is proposed. Platelets (euglobulin from platelet rich plasma and from human platelet extract) may potentiate plasminogen activation by tissue plasminogen activator (tPA). The potentiating activity was detected by both chromogenic substrate and fibrin plate analysis. The fibrinolysis-potentiating substance in the platelets required the presence of both tPA and plasminogen, suggesting that it potentiates the activation of plasminogen by tPA. This substance was not related to fibrinogen degradation products because it was also present in platelets from two afibrinogenemic patients and did not lose its activity when separated from fibrinogen-related antigen by Sepharose 2B gel filtration. Since platelets contain both activator(s) and inhibitor(s) of plasminogen activation by tPA, a balance between activator(s) and inhibitor(s) in platelets may also be required for control of the fibrinolytic pathway.

Antigen-Antibody Complex↗