In mice, trophoblasts are equipped with a potent anticoagulant mechanism, the protein C pathway. In human placenta, no functional studies of the protein C pathway are available. Human first-trimester trophoblasts (CK++ HLA-G(+/-) Vim(-) ) were isolated and kept in culture for a maximum of 48 hours. Activation of protein C on trophoblasts was at least as efficient as in endothelial cells (4.43 x 10 (-) (7) nmol/L/min/cell). Endothelial protein C receptor (EPCR) was expressed in syncytiotrophoblasts and extravillous trophoblasts. Downregulation of the messenger RNA of trophoblast EPCR occurred when trophoblasts were challenged with tumor necrosis factor , and it could be prevented by unfractionated heparin but not by low-molecular-weight heparin at therapeutic doses. In conclusion, there is a functional protein C pathway on human first-trimester trophoblasts which can be modulated by inflammation. This finding has implications for the pathogenesis and prevention of placenta-mediated obstetric complications.
Activation of protein C in human trophoblasts in culture and downregulation of trophoblast endothelial protein C receptor by TNF-α / E.M. Faioni, G. Fontana, C. Razzari, L. Avagliano, G. Bulfamante, E. Calvi, P. Doi, A.M. Marconi. - In: REPRODUCTIVE SCIENCES. - ISSN 1933-7191. - 22:8(2015 Aug), pp. 1042-1048.
Activation of protein C in human trophoblasts in culture and downregulation of trophoblast endothelial protein C receptor by TNF-α
E.M. Faioni
;C. Razzari;L. Avagliano;G. Bulfamante;A.M. MarconiUltimo
2015
Abstract
In mice, trophoblasts are equipped with a potent anticoagulant mechanism, the protein C pathway. In human placenta, no functional studies of the protein C pathway are available. Human first-trimester trophoblasts (CK++ HLA-G(+/-) Vim(-) ) were isolated and kept in culture for a maximum of 48 hours. Activation of protein C on trophoblasts was at least as efficient as in endothelial cells (4.43 x 10 (-) (7) nmol/L/min/cell). Endothelial protein C receptor (EPCR) was expressed in syncytiotrophoblasts and extravillous trophoblasts. Downregulation of the messenger RNA of trophoblast EPCR occurred when trophoblasts were challenged with tumor necrosis factor , and it could be prevented by unfractionated heparin but not by low-molecular-weight heparin at therapeutic doses. In conclusion, there is a functional protein C pathway on human first-trimester trophoblasts which can be modulated by inflammation. This finding has implications for the pathogenesis and prevention of placenta-mediated obstetric complications.Pubblicazioni consigliate
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