title: Modulation of factors involved in placental haemostasis and angiogenesis by low-molecular-weight-heparins.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: 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. e.grandone@operapadrepio.it.
authors: Elvira
authors: E
authors: Grandone
authors: 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.
authors: Elena
authors: E
authors: Chinni
authors: 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.
authors: Michela
authors: M
authors: Villani
authors: Obstetrics and Gynaecology Department, I.R.C.C.S. 'Casa Sollievo della Sofferenza', S. Giovanni Rotondo, Foggia, Italy.
authors: Natale
authors: N
authors: Sciannamè
authors: 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.
authors: Giovanni L
authors: GL
authors: Tiscia
authors: 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.
authors: Giovanni
authors: G
authors: Favuzzi
authors: 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.
authors: Filomena
authors: F
authors: Cappucci
authors: Obstetrics and Gynaecology Department, I.R.C.C.S. 'Casa Sollievo della Sofferenza', S. Giovanni Rotondo, Foggia, Italy.
authors: Francesco
authors: F
authors: Petruzzelli
authors: Medical Genetics, University of Foggia, Foggia, Italy.
authors: Maurizio
authors: M
authors: Margaglione
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010920:Placenta / Q000737:chemistry / Q000502:physiology*; D011247:Pregnancy; D013925:Thromboplastin / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D006023:Glycoproteins; D006495:Heparin, Low-Molecular-Weight; D042461:Vascular Endothelial Growth Factor A; C021240:tissue-factor-pathway inhibitor 2; D013925:Thromboplastin
keywords: Gestational vascular complications; Low-molecular-weight-heparins; Tissue-factor; Vascular endothelial growth factor