Disease relevance of PLG

• Coronary thrombolysis, an intervention that can abort the sequelae of acute myocardial infarction, was accomplished within 10 minutes in dogs by intravenous administration of clot-selective, tissue-type plasminogen activator [1].
• Endogenous prostaglandin endoperoxides and prostacyclin modulate the thrombolytic activity of tissue plasminogen activator. Effects of simultaneous inhibition of thromboxane A2 synthase and blockade of thromboxane A2/prostaglandin H2 receptors in a canine model of coronary thrombosis [2].
• Thrombus was injected at this site, and tissue plasminogen activator was administered, producing cyclic flow variations (CFVs) in 24 of 25 dogs [3].
• Treatment of canine embolic pulmonary hypertension with recombinant tissue plasminogen activator. Efficacy of dosing regimes [4].
• The Km(app) for the activation of dog plasminogen by E. coli outer membrane preparations is similar to the Km(app) for the activation of dog plasminogen by human urokinase [5].

High impact information on PLG

• Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue-type plasminogen activator in dogs [6].
• Visualization of thrombi in pulmonary arteries with radiolabeled, enzymatically inactivated tissue-type plasminogen activator [7].
• Fibrolase does not rely on plasminogen activation or any other bloodborne components for activity and is not inhibited by any of the rapidly acting serine proteinase inhibitors in blood [8].
• In one group of dogs, activated type 1 plasminogen activator inhibitor (PAI-1) (130 micrograms) was delivered directly into the forming thrombus; in another, TXA (110 mg/kg) was given intravenously before thrombus formation; in controls, thrombus was induced without inhibitors [9].
• Canine plasminogen activator (PA) activity (2.6 +/- 1.1 IU/mL acidified platelet-poor plasma [PPP], < 0.3 IU/mL acidified whole blood serum [WBS], mean +/- SD; n = 6) and PA inhibitor activity (6.1 +/- 2.6 U/mL PPP, 35.4 +/- 7.8 U/mL WBS; n = 6) were determined in standard plasminogen-based chromogenic assays [10].

Chemical compound and disease context of PLG

• After 3 hours of thrombus formation in coronary arteries, tissue plasminogen activator and heparin were administered intravenously [11].
• Acceleration of recombinant tissue-type plasminogen activator-induced thrombolysis and prevention of reocclusion by the combination of heparin and the Arg-Gly-Asp-containing peptide bitistatin in a canine model of coronary thrombosis [12].
• To address this possibility, we examined the effect of argatroban [MCI9038, (2R,4R)-4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid], a specific thrombin inhibitor, on the response to tissue-type plasminogen activator in a closed-chest canine model of coronary thrombosis [13].
• OBJECTIVES: This study was designed to determine in a dog model of coronary thrombosis whether short-term eptifibatide (Ep) combined with low-dose plasminogen activator (rt-PA) inhibits platelet recruitment at sites of endothelial damage after normalization of platelet function [14].
• BACKGROUND AND PURPOSE: The two objectives of this study were to assess the potential of BAY U 3405 to prevent arterial thrombosis in response to vessel wall injury and to determine the ability of BAY U 3405 to prevent thrombotic reocclusion after thrombolysis with anisoylated plasminogen streptokinase activator complex [15].

Biological context of PLG

• The efficiency of the uncleaved secretion signal in the plasminogen activator inhibitor type 2 protein can be enhanced by point mutations that increase its hydrophobicity [16].
• Studies of the reaction at high streptokinase levels with the active center reagent, p-nitrophenyl-p-guanidinobenzoate showed that only a fraction (13%) of the potential active centers were developed in a equimolar mixture of streptokinase and dog plasminogen in 15s and more than 10 min were required for the formation of 1 mol of active sites [17].
• Bleeding time prolongation and bleeding during infusion of recombinant tissue-type plasminogen activator in dogs: potentiation by aspirin and reversal with aprotinin [18].
• F(ab')2 fragments of a murine monoclonal anti-platelet GPIIb/IIIa antibody (7E3) are a potent platelet aggregation inhibitor, which in a canine coronary artery thrombosis model accelerate lysis with recombinant tissue-type plasminogen activator (rt-PA) and prevent reocclusion (7) [19].
• Therapeutic defibrination was verified in Ancrod-treated dogs by measurements of clottable fibrinogen, alpha-2 antiplasmin and plasminogen, by the activated partial thromboplastin time and by immunoelectrophoresis [20].

Anatomical context of PLG

• Does tissue-type plasminogen activator have direct beneficial effects on the myocardium independent of its ability to lyse intracoronary thrombi [21]?
• LY210825, a recombinant tissue-type plasminogen activator (rt-PA), which contains the kringle-2 and serine protease functional domains of native tissue-type plasminogen activator, was previously produced by site-directed mutagenesis in a Syrian hamster cell line [22].
• Macrophage-stimulating protein (MSP) and hepatocyte growth factor/scatter factor (HGF/SF) are plasminogen-related growth and motility factors that interact with cell-surface protein tyrosine kinase receptors [23].
• In a second group, thrombi were formed initially in both carotid arteries, BAY U 3405 was administered as before, and anisoylated plasminogen streptokinase activator complex was infused in the right carotid artery proximal to the occlusive thrombus [15].
• Tissue plasminogen activator in the trabecular endothelium [24].

Associations of PLG with chemical compounds

• Counter-ionic interaction between the primary amine group of Huperzine A and the carboxylic terminal group of PLG polymers improves the encapsulation of Huperzine A, reducing the initial burst and extending the sustained release [25].
• Enhancement of thrombolysis with tissue-type plasminogen activator by pretreatment with heparin [26].
• Role of thrombin and thromboxane A2 in reocclusion following coronary thrombolysis with tissue-type plasminogen activator [13].
• Concurrent nitroglycerin administration decreases thrombolytic potential of tissue-type plasminogen activator [27].
• Short-term intravenous eptifibatide infusion combined with reduced dose recombinant tissue plasminogen activator inhibits platelet recruitment at sites of coronary artery injury [14].

Other interactions of PLG

• Plasminogen activator inhibitor-1 activity decreased during rt-PA infusion and thereafter increased in all dogs, but less so in dogs given lys-plasminogen (p < 0.05 vs. those given saline solution before rt-PA) [28].
• Effect of acute smoke inhalation on angiotensin converting enzyme, plasminogen activator, and angiotensin-II in the dog [29].
• In addition, FR167653 significantly inhibited release of both endothelin-1 and plasminogen activator inhibitor-1 from the liver cells [30].

Analytical, diagnostic and therapeutic context of PLG

• Influence of temperature on the conformation of canine plasminogen: an analytical ultracentrifugation and dynamic light scattering study [31].
• Initial thrombolysis after intravenous infusion of tissue-type plasminogen activator (1 mg/kg over 30 minutes) was less frequent in the preparation producing platelet-rich thrombi than in that producing fibrin-rich thrombi (lysis in 19 of 24 versus 18 of 18, p = 0.06) [32].
• Augmented and sustained plasma concentrations after intramuscular injections of molecular variants and deglycosylated forms of tissue-type plasminogen activators [33].
• These experimental animal models may be useful in the development of improved thrombolytic strategies using plasminogen activators in conjunction with specifically targeted antiplatelet and anticoagulant agents [34].
• The aim of thrombolytic therapy for acute myocardial infarction with plasminogen activators such as streptokinase is to lyse the coronary thrombus and reestablish blood flow as quickly as possible so that heart tissue loss is minimized and mortality rates are improved [35].

References