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Modulation of factors involved in placental haemostasis and angiogenesis by low-molecular-weight-heparins

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

In placentae from uneventful pregnancies a direct relationship between expression of tissue factor (TF) and tissue-factor pathway inhibitor type 2 (TFPI2) was found, as well as between TF and vascular endothelial growth factor (VEGF). Furthermore, placentae from gestational vascular complications (GVCs) lack these correlations. Aims of the present study are (1) to evaluate a possible role of low-molecular-weight-heparins (LMWHs) in the modulation of the expression of TF, TFPI, TFPI2 and VEGF in placentae from thrombophilic women and (2) to study the possible role of endothelium in the placental expression of markers involved in haemostasis and angiogenesis.

Methods

Fourteen pregnancies in thrombophilic women and 11 uneventful pregnancies in non-thrombophilic women were studied and placentae collected. From each placenta total RNA was obtained. Expression of TF, TFPI, TFPI2 and VEGF was evaluated. Human Vein Endothelial Cells were incubated with increasing doses of LMWH and expression of TF, TFPI and VEGF was measured.

Results

Expression of all the markers analyzed in placentae from treated pregnancies was similar to that observed in placentae from uneventful ones. A significant direct relationship between TF and TFPI2, as well as TF and VEGF, was observed in cases treated with LMWHs and controls. Furthermore, the expression of TF and its inhibitors and VEGF in endothelial cells was modulated by LMWH.

Conclusion

Present data suggest that LMWH during pregnancy in thrombophilic women restores the relationship between markers of haemostasis and angiogenesis. Furthermore, the endothelium is likely to play an important role in this phenomenon.

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Acknowledgments

We thank Dr. E. Mangiullo for collecting samples.

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Authors and Affiliations

  1. Atherosclerosis and Thrombosis Unit, I.R.C.C.S. ‘Casa Sollievo della Sofferenza’, Poliambulatorio Giovanni Paolo II, Viale Padre Pio, S. Giovanni Rotondo, Foggia, Italy

    Elvira Grandone, Elena Chinni, Michela Villani, Giovanni L. Tiscia, Giovanni Favuzzi & Filomena Cappucci

  2. Obstetrics and Gynaecology Department, I.R.C.C.S. ‘Casa Sollievo della Sofferenza’, S. Giovanni Rotondo, Foggia, Italy

    Natale Sciannamè & Francesco Petruzzelli

  3. Medical Genetics, University of Foggia, Foggia, Italy

    Maurizio Margaglione

Authors
  1. Elvira Grandone
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  2. Elena Chinni
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  3. Michela Villani
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  4. Natale Sciannamè
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  5. Giovanni L. Tiscia
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  6. Giovanni Favuzzi
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  7. Filomena Cappucci
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  8. Francesco Petruzzelli
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  9. Maurizio Margaglione
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Correspondence to Elvira Grandone.

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Grandone, E., Chinni, E., Villani, M. et al. Modulation of factors involved in placental haemostasis and angiogenesis by low-molecular-weight-heparins. Arch Gynecol Obstet 294, 1323–1329 (2016). https://doi.org/10.1007/s00404-016-4185-8

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  • DOI: https://doi.org/10.1007/s00404-016-4185-8

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