[26-OR]: The effect of IgG (AT1-AA) from preeclampsia sera on the production of sEng and various kinds of cytokines from human primary trophoblast cells

Objectives The soluble endoglin (sEng) is an antiangiogenic protein inhibiting TGF- β signaling and eNOS activation. It is well known the levels of sEng increase in preeclamptic patients. However, the factors increasing the sEng in preeclampsia remains poorly understood. In preeclampsia, many autoantibodies such as antiphospholipid, angiotensin II type IA receptor autoantibody (AT1-AA) have been reported. To investigate factors increasing sEng in preeclampsia, we studied the effect of IgG from preeclampsia sera on the production of sEng from human trophoblast cells. Methods Serum samples were from women with normal pregnancies and those with preeclampsia. Villous tissues were from healthy pregnant women having artificial abortion. IgGs isolated from normal pregnancy and preeclampsia sera were eluted by Protein G affinity chromatography. To investigate the possibility of AT1-AA, the production and mRNA expression of sEng were evaluated by AT1-receptor antagonist (losaltan). We also analyzed the various kinds of cytokine productions with or without losartan to find the relationship between sEng, AT1-AA and cytokine productions. Results The addition of preeclampsia IgG into primary trophoblast led to increased release of sEng and increased expression of Eng mRNA. The increased production and mRNA expression of sEng were blocked by the treatment of losartan. The production of TGF- β was increased under the presence of losartan. We considered this effect comes from the decreased production of sEng with losaltan. Conclusions We suggest that AT1-AA in IgG fraction from preeclampsia may play an important role of high level of serum sEng in preeclampsia. Disclosures Y. Koabayshi: None. T. Yamamoto: None. F. Chishima: None. T. Murase: None. H. Azuma: None. A. Nakamura: None. H. Takahashi: None.