AQP9 in preeclampsia

DAMIANO ALICIA E

Los Cocos, Cordoba- Argentina

Simposio; III Latin-American Symposium on Maternal-Fetal Interaction and Placenta:Basic & Clinical Research; 2007

Placental Association of America

Preeclampsia (PE) is a hypertensive disorder unique to human pregnancy. Its etiology remains unknown, but it is characterized by abnormal trophoblast invasion giving rise to a hypoxic tissue with an over expression of Hypoxia Inducible Factor-1alpha protein (HIF-1alpha). Thus, altered placental villous angiogenesis and poorly developed fetoplacental vasculature can affect the transport functions of the syncytiotrophoblast (hST).Previously, we reported an increase AQP9 molecular expression in preeclamptic placentas, with a decrease of water unidirectional fluxes. Our work is focused on establishing the mechanisms that may modulate AQP9 expression and functionality. Using cultured explants we demonstrated that was not responsible of AQP9 over expression.AQP9 molecular expression and activity was reduced. AQP9 gen has a negative insulin-response-element. Recently, we postulated that insulin resistance could modulate AQP9 expression. In PE, insulin levels are augmented but insulin is not effective to down regulate AQP9 expression. Here, we investigate if AQP9 lack of activity in PE is associated with alterations in plasma membrane composition which can affect membrane order, fluidity and lipid-protein interactions. There is strong evidence that cystic fibrosis transmembrane conductance regulator (CFTR) regulates AQP9 functionality. In PE, we showed for the first time that in apical membranes of hST, sphingomielin augmented 1.5 fold without changes in cholesterol levels. These changes in the phospholipid composition may affect CFTR expression in hST. We demonstrated by molecular biology that CFTR expression decreased in preeclamptic placentas and it did not co- localize with AQP9. These results suggest that the altered phospholipid composition in PE may contribute with a non-favorable environment for CFTR. CFTR failed to regulate AQP9 activity.