The Regulation of Fatty Acid Oxidation in Human Preeclampsia

摘要

Preeclampsia (PE) is a pregnancy disorder characterized by high blood pressure, placental oxidative stress, and proteinuria. In a GeneFishing experiment using human preeclamptic placenta, expression of acyl-coenzyme A dehydrogenase very long chain (ACADVL), which is involved in fatty acid -oxidation (FAO), was detected. To investigate the correlation between PE and FAO, this study subjected in vitro BeWo cells and in vivo pregnant mice to oxidative stress induced by hypoxia. Hypoxic condition, which oxygen supply is insufficient in cells and placenta, created a similar state to placental oxidative stress in PE, as evidenced by increased hypoxic (oxoguanine DNA glycosylase 1, hypoxia inducible factor 1 alpha subunit) and preeclamptic markers (soluble fms-like tyrosine kinase 1) both in vitro and in vivo. Increased expression of FAO-related genes (ACADVL, enoyl-coenzyme A hydratase/3-hydroxyacyl coenzyme A dehydrogenase) was observed in these models as well as in cases of preeclamptic preterm labor. In the in vivo liver model, messenger RNA expression of gluconeogenesis-related genes increased. Consequently, these results suggest that expression of FAO-related genes is regulated by hypoxic conditions and onset time of PE and affects maternal gluconeogenesis during pregnancy in patients with PE.