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Placental Productions and Expressions of Soluble Endoglin, Soluble fms-Like Tyrosine Kinase Receptor-1, and Placental Growth Factor in Normal and Preeclamptic Pregnancies

Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana 71130

Address all correspondence and requests for reprints to: Yuping Wang, M.D., Ph.D., Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center-Shreveport, P.O. Box 33932, Shreveport, Louisiana 71130. E-mail: ywang1{at}lsuhsc.edu.

Context: Increased production of antiangiogenic factors soluble endoglin (sEng) and soluble fms-like tyrosine kinase receptor-1 (sFlt-1) by the placenta contributes to the pathophysiology in preeclampsia (PE).

Objective: Our objective was to determine the differences in endoglin (Eng), fms-like tyrosine kinase receptor-1 (Flt-1), and placental growth factor (PlGF) expressions between normal and PE placentas and sEng, sFlt-1, and PlGF production by trophoblast cells (TC) cultured under lowered oxygen conditions.

Methods: TCs isolated from normal and PE placentas were cultured under regular (5% CO₂/air) and lowered (2% O₂/5% CO₂/93% N₂) oxygen conditions. sEng, sFlt-1, and PlGF productions were determined by ELISA. Protein expressions for Eng, Flt-1, and PlGF in the placental tissues were accessed by immunohistochemical staining and Western blot analysis. Deglycosylated Eng, Flt-1, and PlGF protein expressions in placental tissues were also examined.

Results: PE TCs produced significantly more sEng, sFlt-1, and PlGF compared with those from normal TCs (P < 0.05). Under lowered oxygen conditions, PE TCs, but not normal TCs, released more sEng and sFlt-1. In contrast, both normal and PE TCs released less PlGF (P < 0.05). Enhanced expressions of Eng and Flt-1, as well as glycosylated Eng and Flt-1, were observed in PE placentas. Immunoblot also revealed that TCs released glycosylated sFlt-1, but not sEng, in culture.

Conclusions: PE TCs produce more sEng, sFlt-1, and PlGF than normal TCs. Lowered oxygen conditions promote sEng and sFlt-1, but reduce PlGF, productions by PE TCs. More glycosylated sEng and sFlt-1 are present in PE placentas. Trophoblasts release glycosylated sFlt-1, but unglycosylated sEng, in culture.