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428: Preeclampsia is characterized by decreased expression of endothelin converting enzyme-1 in the placenta

      Objective

      Endothelin-converting enzyme 1 (ECE-1) is a key regulatory enzyme in the proteolytic processing of Endothelin-1 (ET-1), a potent vasoactive peptide. In most vascular beds, ECE-1 localizes to endothelial cells, but has not been extensively studied in the human placenta. We sought to evaluate the expression and cellular localization of ECE-1 in normal and preeclamptic placentas.

      Study Design

      Placentas from normal (n=6) and preeclamptic (n=6) women, matched for gestational age, were collected and serially sectioned for immunofluorescence (IF) studies to localize ECE-1 expression. Cell type specific markers were used to identify the following cell types: endothelial, trophoblast, macrophage, smooth muscle and fibroblast cells. The samples were stained with antibodies for ECE-1 and tissue markers and counterstained with DAPI. Negative controls were stained with secondary antibodies and DAPI. Quantitative analysis of ECE-1 within placenta samples was performed by western blot and ELISA.

      Results

      Immunofluorescence studies confirmed ECE-1 expression within the stroma and villous spaces of intermediate and stem villi of human placentas. Localization of ECE-1 occurred occasionally with endothelial cells but not with the other cell types evaluated (Figure 1). IF studies suggested less ECE-1 expression in preeclamptic placentas. Western blot and ELISA showed significantly less ECE-1 in preeclamptic compared with normal placentas (Figure 2).

      Conclusion

      ECE-1 is expressed in the villous spaces of the human placenta. There is significantly less ECE-1 expression in preeclamptic versus normal placentas. ECE-1 likely plays an important role in vascular homeostasis in the placenta and may be protective against disorders of vascular dysfunction, such as preeclampsia. The lack of colocalization of ECE-1 suggests a secreted form of the enzyme, however further study is needed to confirm this.
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