tPA inhibitor, tPA:Ag, plasminogen, and α2-antiplasmin after low molecular weight heparin or standard heparin

Neerstrand, H.; Østergaard, Per; Bergqvist, David; Mätzsch, Thomas; Hedner, Ulla

doi:10.1016/0268-9499(87)90031-2

Cited by 27 publications

(7 citation statements)

References 11 publications

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“…Both tPA and PAI-1 are subject to diurnal variation with highest levels in the early morning for PAI-1 activity and highest concentrations in the afternoon for tPA activity. This may offer an explanation to the higher incidence of myocardial infarction in the early morning (216,217).…”

Section: Paper IIImentioning

confidence: 96%

The complex between tPA and PAI-1: risk factor for myocardial infarction as studied in the SHEEP project

Nordenhem

Leander

Hallqvist

et al. 2005

Thrombosis Research

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Section: Paper IIImentioning

confidence: 96%

The complex between tPA and PAI-1: risk factor for myocardial infarction as studied in the SHEEP project

Nordenhem

Leander

Hallqvist

et al. 2005

Thrombosis Research

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“…The influence of heparin on the fibrinolytic system has been a matter of controversy for many years. In some in vivo studies increased fibrinolytic activity in plasma after heparin administration has been reported (25)(26)(27)(28), while other investigators could not find an effect of heparin on the fibrinolytic system (29,30). Experiments using animal perfusion models demonstrated enhanced release of plasminogen activators by heparin and heparin-like substances (26,28,31).…”

Section: Discussionmentioning

confidence: 99%

Heparin Stimulates Fibrinolysis in Mesothelial Cells by Selective lnduction of Tissue-Plasminogen Activator but not Plasminogen Activator Inhibitor-l Synthesis

Grulich‐Henn¹,

Preissner²,

Müller‐Berghaus³

1990

Thromb Haemost

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SummaryThe regulation of tissue-plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-l) synthesis was studied in cultured human mesothelial cells derived from omentum (HOMC). Heparin (100 U/ml) as well as pentosan polysulfate (300 pg/mt) stimulated tPA synthesis by HOMC 2.9-4.5-fold. Heparin-induced tPA production was dose- and time-dependent and was inhibited by cycloheximide. tPA production by HOMC was also stimulated by phorbol 12-myristrate l3-acetat (2.6-fold), fibrin clots (1.9-fold), or batroxobin (1.9-fold).Heparin and pentosan polysulfate did not stimulate PAI-1 production by HOMC, while phorbol l2-myristrate 13-acetat (100 nM) increased the concentration of PAI-1 in the conditioned medium by 2.6-fold over 24 h. The interaction of heparin with HOMC was studied by direct binding experiments. Dose-dependent specific binding of biotinylated heparin to HOMC was saturable at about 10 pg/ml, the Kp was estimated to about 0.15 pM. Biotinylated heparin bound rapidly to HOMC and reached a plateau within 60 min. Unlabeled heparin as well as pentosan polysulfate inhibited binding of biotinylated heparin in a dose-dependent fashion. These data demonstrate that heparin interacts with HOMC, and increases the fibrinolytic capacity in these cells by selectively increasing the production of tPA.

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“…2. Prior to infusion average PAI-1 Ag levels were similar (14 ng/ml [range [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] [heparin], 13 [7][8][9][10][11][12][13][14][15][16][17][18][19] [Org 10172] and 13 [7][8][9][10][11][12][13][14][15][16][17][18] [saline]; p >0.05). This was also the case for values at 14 min following drug administration (10 ng/ml [range 6-20], 10 [6-14] and 10 [5-14], respectively; p >0.05).…”

Section: Pharmacokinetic Parameters Of Rt-pamentioning

confidence: 99%

“…There is general agreement that their main mechanism of action is through inhibition of the coagulation cascade although enhancement of fibrinolytic activity may be an additional pathway. The latter, however, is uncertain, mainly because the effects of heparin on endogenous fibrinolysis are still not well established, Whilst some in vitrp, animal and human experiments have demonstrated an enhancement of fibrinolytic activity by sulfated polysaccharides (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), there are also a number of studies which show the opposite (absence of effect or even inhibitory effects on fibrinolysis) (19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Influence of Heparin and a Low Molecular Weight Heparinoid on Specific Endogenous and Exogenous Fibrinolytic Factors during Rest and Exercise

Boer

Kluft²,

Dooijewaard³

et al. 1992

Thromb Haemost

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SummaryThe effects of heparin (5,000 IU i.v.) and the low molecular weight heparinoid Org 10172 (Orgaran®) (3,250 anti-Xa units i. v.) on components of the fibrinolytic system were studied in two double-blind, randomised, placebo-controlled, cross-over trials using healthy subjects. In study A (n = 6) the effects were studied during rest and standardized exercise and in study B (n = 6) during a low dose infusion of recombinant tissue-type plasminogen activator (rt-PA; 80 µg over 16 min). At rest, heparin and Org 10172 did not influence the plasma concentrations of endogenous t-PA antigen, and activity, urokinase-type PA (u-PA) antigen, plasmin activatable pro-urokinase (scu-PA), active urokinase (tcu-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen. Recombinant t-PA antigen and activity during rt-PA infusion were also not affected. During exercise, neither heparin nor Org 10172 influenced the area under the curve (AUC) of t-PA and u-PA antigen and t-PA activity when compared with placebo. Unexpectedly, after heparin the AUC of t-PA activity was 49% larger (range +19 to +245%) than after Org 10172 (p <0.05). The last difference was considered spurious. scu-PA, tcu-PA and PAI-1 antigen levels at 2 min after termination of exercise were unaffected by both compounds (p >0.05). Sulphated polysaccharides do not increase fibrinolytic activity of the plasma by changing the concentrations of the components of the fibrinolytic system.

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tPA inhibitor, tPA:Ag, plasminogen, and α2-antiplasmin after low molecular weight heparin or standard heparin

Cited by 27 publications

References 11 publications

The complex between tPA and PAI-1: risk factor for myocardial infarction as studied in the SHEEP project

The complex between tPA and PAI-1: risk factor for myocardial infarction as studied in the SHEEP project

Heparin Stimulates Fibrinolysis in Mesothelial Cells by Selective lnduction of Tissue-Plasminogen Activator but not Plasminogen Activator Inhibitor-l Synthesis

Influence of Heparin and a Low Molecular Weight Heparinoid on Specific Endogenous and Exogenous Fibrinolytic Factors during Rest and Exercise

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