Trophoblastic Debris Extruded From Placentae Activates Endothelial Cells And The Possible Mechanism

Preeclampsia is a pregnancy-specific disorder which characterized by hypertension, proteinuria and widespread maternal endothelial dysfunction. The pathogenesis’of preeclampsia is unclear, but it is well accepted that the presence of placenta is responsible for the development of preeclampsia. It is suggested that trophoblastic debris shed from placenta changing from being apoptosis-like to being more necrotic contributes to the pathogenesis of preeclampsia. But whether trophoblastic debris produced by preeclamptic placentae activates the endothelium remains unansweredIn this study, we investigated whether trophoblastic debris from preeclamptic placentae activated endothelial cells and the possible mechanism, and whether syncytiotrophlast microparticles from placentae can be phagocytosed and absorbent by endothelial cells and subsequently modifying the response of endothelial cells to STBM, so as to supply experimental evidence for the pathophysiology of endothelial cell activation and target of clinical treatment of preeclampsia.1. Trophoblastic debris extruded from preeclamptic placentae activates endothelial cells in an IL-1β associated pathway Objectives:Investigated whether trophoblastic debris from preeclamptic placentae activated endothelial cells and the role of IL-1β in the activation of endothelial cells. Method:Trophoblastic debris from preeclamptic or normotensive placentae were exposed to endothelial cells. Furthermore, trophoblastic debris from normal first trimester placental explants that were cultured individually with preeclamptic or normotensive sera was also exposed to endothelial cells. Endothelial cell activation 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 trophoblastic debris were measured. To confirm the role of IL-1β on inducing endothelial cell activation, endothelial cells were treated with human recombinant IL-1 p for 24 hours. Results:Compared to controls, the levels of ICAM-1 and U937 adhesion to endothelial cells were significantly increased following exposure of the endothelial cells to trophoblastic 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 trophoblastic debris from preeclamptic placentae and placentae treated with preeclamptic sera.Conclusion:These results suggest trophoblastic debris produced in preeclamptic pregnancies or in placentae treated with preeclamptic sera activated endothelial cells. Trophoblastic debris containing IL-1β may be one mechanism to induce endothelium activation in preeclampsia.2. The role of syncytiotrophoblastic microparticles on endothelial activationObjectives:Investigate whether syncytiotrophlast microparticles from placentae can be phagocytose and absorbent by endothelial cells and subsequently modifying the response of endothelial cells to STBM.Method:To detect the ability of phagocytosis and clearance of STBM, STBM were incubated with the confluent monolayers of endothelial cells for 24 hours, the cells were then examined by confocal microscopy using a Leica model TCS SP2 confocal microscope. Normal first trimester placental explants were cultured individually with preeclamptic or normotensive sera, then STBM were collected and exposed to endothelial cells. Endothelial cell activation was quantified by cell surface ICAM-1. The levels of IL-1β in conditioned medium from endothelial cells cultured with STBM were also quantified by ELISA.Results:Endothelial cells phagocytose STBM and the phagocytosis of STBM was significantly inhibited by cytochalsin D, an inhibitor of phagocytosis. Phagocytosis of STBM was increased in a time dependent manner Endothelial cell became activated by the phagocytosis of STBM from placental explants that was treated with preeclamptic sera, with increased expression of ICAM-1 and releasing of IL-1β in conditioned medium.Conclusion:Endothelial cells phagocytose trophoblast microparticles from placental explants, and microparticles from placental explants treated with preeclamptic, but not normotensive sera activated the phagocytosing endothelial cells as indicated by increased ICAM-1 and IL-1 b expression..In conclusion, trophoblastic debris extruded from preeclamptic placenta activates endothelial cells in an IL-1β associated pathway, STBM can be phagocytosed and absorbent by endothelial cells in a time dependent manner and STBM from placental explants treated with preeclamptic but not normotensive sera induce endothelial cells activation. These results indicate trophoblastic debris is a placental factor which induce endothelial cell dysfunction, and may be used as a therapeutic target for preeclampsia.