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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. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Preeclampsia (PE) and fetal growth restriction (FGR) are multifactorial diseases, whose pathogenesis is largely unknown. A significant relationship between haemostasis and angiogenesis in placentae from uneventful pregnancies was previously shown. Materials and Methods: RNA expression of haemostasis (TF, TFPI, TFPI-2, PAI-2, Anx V, TM) and angiogenesis (Ang-1, Ang-2, PlGF, VEGF) markers in placentae from PE (n=12), PE+FGR (n=17) and FGR (n=20) in respect of placentae from uncomplicated pregnancies (n=21) were investigated. Results: Placentae from complicated pregnancies showed a significant lower expression (p≤0.05 Mann-Whitney U test) of TF, TFPI, TFPI-2, Anx V, PAI-2 than those from in uncomplicated ones. VEGF and PlGF were not different in the considered groups; Ang-1 and Ang-2 were significantly higher (p≤0.05 Mann-Whitney U test) in the PE group. Correlations between factors involved in haemostasis and those involved in angiogenesis, observed in placentae from uneventful pregnancies are lacking in those from complicated ones. Conclusions: Haemostasis factors are reduced in placentae from complicated pregnancies. The relationship between haemostasis and angiogenesis observed in uncomplicated pregnancies is impaired in PE and FGR. [Copyright &y& Elsevier]