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

Abstract

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.

Coagulation activation after laparoscopic cholecystectomy in spite of thromboembolism prophylaxis

“…This effect could be beneficial, since vWf has been shown to correlate to an increased risk of venous thromboembolism [4]. Likewise, the finding that LMWH (and unfractioned heparin) increases tPA levels is not new [7]. This effect could also be of benefit, since an increase in fibrinolysis could counteract the development of manifest thrombosis.…”

A 6-month Venographic Follow-up in 164 Patients with Acute Deep Vein Thrombosis

“…No other variable had any independent impact on tluombus evolution. e (18) BQA l (2) | (2) 6 (21) t2 418 (28) I (3) 2 (7) vt (4e) tt 237 (14) s (10) 2 (4) 8 (22) t7 (46) t2 patients. The Marder score was higher at the first venography and the absolute resolution of the thrombus was enhanced in males.…”

“…This result could be explained by the fact that UFH has a larger impact on the endothelium or on the reticuloendothelial system (with less clearance of t-PA) than LMWH. In experimental studies, LIFH has been shown to stimulate endothelial cells and increase the production of t-PA to a greater extent than LMWH (17,18). The fibrinolytic parameters t-PA-Ag and PAI-I…”

Macrophage-colony forming cells (M-CFC), with different sensitivities to colony stimulating factors, from peritoneal exudates and tissues of chronically inflamed mice

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