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.
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.
van Giezen
J J
JJ
Astra Charnwood, Pharmacology, Loughborough, Leicestershire, UK.
Nerme
V
V
Abrahamsson
T
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001792:Blood Platelets / Q000276:immunology / Q000502:physiology*; D005342:Fibrinolysis / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000276:immunology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D013927:Thrombosis / Q000097:blood* / Q000276:immunology; D013997:Time Factors
D000906:Antibodies; D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors