Trophoblast debris extruded from preeclamptic placentae activates endothelial cells: A mechanism by which the placenta communicates with the maternal endothelium |
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Authors: | F. Shen J. Wei S. Snowise J. DeSousa P. Stone C. Viall Q. Chen L. Chamley |
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Affiliation: | 1. The Hospital of Obstetrics & Gynaecology, Fudan University, China;2. Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand;3. Maternal Fetal Medicine, Auckland City Hospital, New Zealand;4. Gravida The National Centre for Growth and Development, The University of Auckland, New Zealand |
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Abstract: | IntroductionPreeclampsia is characterized by maternal endothelial dysfunction. While the mechanisms leading to preeclampsia are unclear, a factor(s) from the placenta is responsible for triggering the disease. One placental factor implicated in triggering preeclampsia is trophoblast debris which may transmit pathogenic signals from the placenta to endothelial cells. In this study, we investigated whether trophoblast debris from preeclamptic placentae triggered endothelial cell activation.MethodsTrophoblast debris from preeclamptic or normotensive placentae, or trophoblast debris from normal placental explants that had been cultured with preeclamptic (n = 14) or normotensive sera (n = 14) was exposed to endothelial cells. Activation of the endothelial cells was quantified by cell surface ICAM-1 and U937 adhesion to endothelial cells. The levels of IL-1β, pro-caspase-1 and active caspase-1 in the trophoblast debris were measured.ResultsCompared to controls, the levels of ICAM-1 and U937 adhesion to endothelial cells were significantly increased following exposure of the endothelial cells to trophoblast debris from preeclamptic placentae or placentae treated with preeclamptic sera. The levels IL-1β, pro-caspase-1 and active caspase-1 were significantly increased in both trophoblast debris from preeclamptic placentae and placentae treated with preeclamptic sera.DiscussionThese results provide the first direct evidence that trophoblast debris produced from preeclamptic placentae or placentae treated with preeclamptic sera can activate the endothelium.ConclusionsTrophoblast debris from preeclamptic but not normotensive placentae can induce endothelial cell activation. This may be one mechanism by which the preeclamptic placenta communicates with the maternal endothelium to induce activation of the endothelium. |
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Keywords: | Preeclampsia Endothelium Trophoblast debris Syncytial nuclear aggregates IL-1β Caspase-1 |
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