Expression of Tissue Factor and TF-mediated integrin regulation in HTR-8/SVneo trophoblast cells

2022 ◽  
pp. 103473
Author(s):  
Mallikarjun Gundappa ◽  
Arumugam Vijaya Anand ◽  
Hsi-Lung Hsieh ◽  
Balamuralikrishnan Balasubramanian ◽  
Velayuthaprabhu Shanmugam
Keyword(s):  
Tissue Factor ◽  
Trophoblast Cells ◽  
Integrin Regulation

scholarly journals Maintaining extraembryonic expression allows generation of mice with severe tissue factor pathway inhibitor deficiency

2019 ◽  
Vol 3 (3) ◽  
pp. 489-498 ◽  
Author(s):  
Michelle M. Castillo ◽  
Qiuhui Yang ◽  
Min Zhan ◽  
Amy Y. Pan ◽  
Michael W. Lawlor ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Brain Ischemia ◽  
Tissue Factor Pathway Inhibitor ◽  
Factor Viia ◽  
Renal Medulla ◽  
In Utero ◽  
Adult Survival ◽  
Trophoblast Cells ◽  
Similar Reduction ◽  
Tissue Factor Pathway

Abstract Tissue factor pathway inhibitor (TFPI) is a serine protease with multiple anticoagulant activities. The Kunitz1 (K1) domain of TFPI binds the active site of factor VIIa and is required for inhibition of tissue factor (TF)/factor VIIa catalytic activity. Mice lacking TFPI K1 domain die in utero. TFPI is highly expressed on trophoblast cells of the placenta. We used genetic strategies to selectively ablate exon 4 encoding TFPI K1 domain in the embryo, while maintaining expression in trophoblast cells. This approach resulted in expected Mendelian frequency of TFPI K1 domain–deficient mice. Real-time polymerase chain reaction confirmed 95% to 99% genetic deletion and a similar reduction in transcript expression. Western blotting confirmed the presence of a truncated protein instead of full-length TFPI. Mice with severe TFPI K1 deficiency exhibited elevated thrombin-antithrombin (TAT) levels, frequent fibrin deposition in renal medulla, and increased susceptibility to TF-induced pulmonary embolism. They were fertile, and most lived normal life spans without any overt thrombotic events. Of 43 mice observed, 2 displayed extensive brain ischemia and infarction. We conclude that in contrast to complete absence of TFPI K1 domain, severe deficiency is compatible with in utero development, adult survival, and reproductive functions in mice. Inhibition of TFPI activity is being evaluated as a means of boosting thrombin generation in hemophilia patients. Our results show that in mice severe reduction of TFPI K1 activity is associated with a prothrombotic state without overt developmental outcomes. We note fibrin deposits in the kidney and rare cases of brain ischemia.

Tissue Factor Activity of Syncytiotrophoblast Plasma Membranes and Tumoral Trophoblast Cells in Culture

1995 ◽  
Vol 73 (01) ◽  
pp. 049-054 ◽  
Author(s):  
P Reverdiau ◽  
A C Jarousseau ◽  
G Thibault ◽  
B Khalfoun ◽  
H Watier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Plasma Membranes ◽  
Umbilical Vein ◽  
Cell Types ◽  
Maximum Effect ◽  
Trophoblast Cells ◽  
Tnf Α ◽  
Normal Human ◽  
Umbilical Vein Endothelial Cells

SummaryDuring pregnancy, important modifications of hemostasis occur resulting in mothers in hypercoagulability and the role of placental cells such as trophoblast cells has been hypothesized. In this study, we first showed that syncytiotrophoblast plasma membranes, isolated from normal human placenta, expressed a strong tissue factor (TF) activity. We then studied TF activity of two continuous trophoblast cell lines (JEG-3 and BeWo) in comparison to human umbilical vein endothelial cells (HUVEC) and transformed human endothelial cells (ECV-304). TF assays were performed on intact detached confluent cells. Unstimulated JEG-3 and BeWo cells exhibited a very high TF activity which slightly increased after 2 to 4 h TNF-α stimulation. In contrast, HUVEC and ECV-304 had a lower basal TF activity which was mainly inducible by TNF-a, with a maximum effect after 4 to 6 h stimulation. For both cell types, TF activity was decreased to basal value after 16-hour TNF-α stimulation. These results support that trophoblast cells are able to express TF but the involvement of this property in the hemostatic physiological changes observed during pregnancy, remains to be demonstrated.

Effects of Radiographic Contrast Agents on Thrombin Formation and Activity

1998 ◽  
Vol 80 (08) ◽  
pp. 266-272 ◽  
Author(s):  
Andrew Parker ◽  
William Fay
Keyword(s):  
Contrast Agents ◽  
Tissue Factor ◽  
Coronary Angioplasty ◽  
Molecular Mechanisms ◽  
Factor Viia ◽  
Minor Effect ◽  
Ionic Contrast ◽  
Radiographic Contrast ◽  
Inhibition Of Thrombin ◽  
Thrombin Formation

SummaryClinical trials suggest that the risk of thrombosis during coronary angioplasty is lower with ionic contrast agents than with nonionic contrast agents. However, the molecular mechanisms underlying this effect are unknown. This study examined the effects of contrast agents on thrombin formation and its interaction with substrates, inhibitors, and ligands to define potential mechanisms by which contrast agents affect thrombus formation. Two ionic agents, diatrizoate and ioxaglate, and one nonionic agent, ioversol, were studied. Ionic agents inhibited factor X activation by the tissue factor-factor VIIa complex more potently than ioversol (53 ± 3.7, 43.0 ± 1.9, and 26.5 ± 2.4% inhibition by diatrizoate, ioxaglate, and ioversol, respectively, at concentrations of 5%). Ionic contrast agents were potent inhibitors of prothrombinase function, inhibiting thrombin formation by >75% at contrast concentrations of 0.6% (p <0.005). Ioversol inhibited prothrombinase to a significantly lesser extent than ionic agents. Clotting assays suggested that ioxaglate was the most potent inhibitor of thrombin generation in plasma despite having the least effect on fibrin polymerization. Contrast agents inhibited binding of thrombin to fibrin, with ionic agents producing a more potent effect than ioversol (p <0.02). However, contrast agents did not inhibit thrombin-mediated platelet activation, had only a minor effect on inhibition of thrombin by antithrombin III, and did not affect thrombin-hirudin interactions. In summary, these studies identify specific mechanisms by which radiographic contrast agents inhibit thrombin formation and function – i.e. inhibition of tissue factor-dependent factor Xa generation, inhibition of the prothrombinase complex, and inhibition of thrombin binding to fibrin. These findings may help to explain the reduced risk of thrombosis during coronary angioplasty associated with ionic contrast agents.

Tissue Factor Signaling

1999 ◽  
Vol 82 (08) ◽  
pp. 175-182 ◽  
Author(s):  
Barbara Mueller ◽  
Wolfram Ruf
Keyword(s):  
Tissue Factor
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