Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of PRAP-1, a Fab-fragment of a PAI-1-inhibiting polyclonal antibody, on thrombus size and arterial blood flow was studied in a rat model of arterial thrombosis. It was shown that exposure of the carotid artery to FeCl3 led to the rapid formation of an occlusive thrombus with a morphology similar to that of arterial thrombi found in humans. Tranexamic acid (50 mg/kg), an inhibitor of fibrinolysis, increased thrombus size (p = 0.014) when given intravenously (i.v.) prior to the FeCl3-exposure. Heparin (1000 U), when given i.v. after FeCl3, did not affect the thrombus size per se, but caused a reduction in the interindividual variation of the size of the thrombus (p < 0.05). Thus, heparin was included in all the subsequent experiments. An i.v. infusion of t-PA (1 mg/kg/h), starting before thrombus formation, induced a 3.3 fold increase in the perfusion rate (p = 0.006) and a 67% reduction in the thrombus size (P < 0.001). PRAP-1, an inhibitor of rat PAI-1 activity, was given i.v. as a bolus followed by an infusion. Two doses of PRAP-1 were studied (7.5 and 15 mg/kg/h), and the administration of the PAI-1 inhibitor was started 10 min before FeCl3. The lower PRAP-1 dose caused a 3.8 fold increase in perfusion rate (p = 0.036), a 1.44 fold increase in the time to occlusion (p = 0.034), and the thrombus size was decreased by 18% (p = 0.104). The corresponding effects of the high PRAP-1 dose were a 6.5 fold increase in perfusion rate (p < 0.001), a 1.6 fold increase in time to occlusion (p = 0.038) and a 32% reduction in thrombus size (p = 0.016). It is concluded that an inhibitor of PAI-1 activity, PRAP-1, caused a moderate decrease in thrombus size and partly restores blood flow in a rat model of arterial thrombus. This finding suggests a potential role for an inhibitor of PAI-1 in the treatment of arterial thrombosis.
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PMID:The Fab-fragment of a PAI-1 inhibiting antibody reduces thrombus size and restores blood flow in a rat model of arterial thrombosis. 918 11

We studied the effects of PRAP-1, a PAI-1-inhibiting polyclonal antibody, on tissue-type plasminogen activator (t-PA)-induced lysis of arterial-like thrombi prepared in vitro from rat and human blood in a Chandler loop device. The t-PA induced lysis of the thrombus head and tail was studied over 5 h. For thrombi prepared from rat blood, the lysis ratio head:tail was (mean +/- SD): 0.71 +/- 0.16 (platelet-poor blood), 0.49 +/- 0.22 (whole blood), and 0.22 +/- 0.12 (platelet-rich blood). PRAP-1 increased the lysis ratio to 0.68 +/- 0.22 for whole-blood thrombi (P < 0.01) and to 0.46 +/- 0.15 for platelet-rich thrombi (P < 0.001). For thrombi formed from human whole blood, PRAP-1 increased the lysis ratio head:tail from 0.61 +/- 0.18 to 0.95 +/- 0.24 (P < 0.05). These effects of PRAP-1 were due to a selective increase in the lysis of the thrombi head. The plasminogen activator inhibitor (PAI-1) activity was 7.5 +/- 2.8 (rat) and 3.4 +/- 1.3 (human) times higher in the thrombus head compared with the tail. In thrombi prepared from rat whole blood, PRAP-1 decreased the PAI-1 activity of the thrombus head only by 38 +/- 7% (P < 0.01), while in thrombi prepared from human whole blood the PAI-1 activity of the thrombus head decreased by 83 +/- 4% (P < 0.001). In conclusion, the lysis resistance of the head of an arterial-like thrombus formed in vitro can be partially (rat) or totally (human) normalized by inhibition of the PAI-1 activity. The results further suggest that in rat arterial-like thrombi a t-PA-inhibiting component, different from PAI-1, is present.
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PMID:PAI-1 inhibition enhances the lysis of the platelet-rich part of arterial-like thrombi formed in vitro. A comparative study using thrombi prepared from rat and human blood. 960 14