The role of autophagy for protein aggregation in preeclampsia

Abstract

Preeclampsia is one of the placenta-mediated pregnancy complications, which includes fetal growth restriction (FGR), late pregnancy loss, or placental abruption. Severe pregnancy complications are related with abnormalities of placentas. In preeclampsia, two stage disorder theory has been proposed for the pathophysiology of preeclampsia: poor placentation is occurred at the first step followed with the systemic endothelial dysfunction at the second step. We, so far, have been focused on the role of autophagy for placentation to clarify the mechanism of development of preeclampsia. The inhibition of autophagy was mediated with the failure of functions, invasion and vascular remodeling, in extravillous trophoblasts (EVTs). In addition, placenta-specific atg7 knockout mice, in which autophagy was impaired in trophoblasts, showed growth restriction in placentas and high blood pressure in dams. On the other hand, neither proteinuria in dams nor FGR were seen in the mice. Taken together, impairment of autophagy was mainly mediated with the first step, but not the second step. Recently, we obtained some new findings related with the protein aggregation by autophagy inhibition, as can be seen in neurodegenerative diseases. In this paper, we review the role of autophagy in preeclampsia.