Hypoxia in the pathogenesis of preeclampsia

Abstract

Oxidative stress is required for the development of hypoxic injury and has been investigated as a key factor in the pathogenesis of preeclampsia. In preeclampsia, hypoxia at the implantation site can contribute to lesion formation, leading to poor placentation. Hypoxia-inducible factor-1α (HIF-1α) is a known transcription factor involved in placentation. Increased levels of HIF-1α can induce secretion of soluble vascular endothelial growth factor receptor-1 (sFlt-1), which is known to be a major factor influencing the pathogenesis of preeclampsia. Meanwhile, HIF-1α and HIF-1β mediate the maintenance and production of endothelial progenitor cells and bone marrow-derived stem cells, which play important roles in placental vascular development. Related dysfunction can result in preeclampsia. It is also known that glycolytic enzyme phosphoglycerate mutase (PGAM) is deacetylated and activated by reactive oxygen species (ROS), the former of which may regulate cell proliferation through the effects of ROS without the participation of HIF-1α. In this review, we characterize the roles of HIF and PGAM in the pathogenesis of preeclampsia.