The Role And Mechanism Of A New Endogenous Polypeptide ELABELA In Preeclampsia

ELABELA/Apela(ELA)is a newly discovered highly conserved secreted polypeptide hormone,which is an endogenous ligand of the G protein-coupled receptor APJ.ELA has been proved to be involved in regulating the apoptosis,self-renewal,cardiovascular development and endodermal differentiation of embryonic stem cells in the process of embryonic development,and is one of the decisive factors of cardiac genesis,especially early embryonic development.Furthermore,ELA also plays a crucial role in promoting angiogenesis,lowering blood pressure,regulating fluid homeostasis,and adjusting cardiovascular function.Pre-eclampsia(PE)is an important obstetric complication newly developed during gestation.The primary clinical manifestations are multiple organ damage,hypertension and proteinuria,which is one of the leading causes of maternal and perinatal death.In recent years,although great progress has been made in the understanding of PE,there is still no definite explanation for its pathogenesis and mechanism.Recent studies have shown that ELA gene deletion can induce pre-eclampsia-like symptoms in mice,which can be alleviated by injection of exogenous ELA peptides.However,the role of ELA in the development of PE is unclear.We have collected the non-pregnant woman's blood and urine,and the blood,urine samples and placental tissue from pregnant women in different periods,the early-onset PE and the late-onset PE,by ELISA to detect serum concentration and urine concentration of ELA,found the ELA in pregnant women blood concentrations increased significantly,late-onset pre-eclampsia patients the ELA levels in the blood is significantly reduced compared with normal pregnant women in pregnancy.Furthermore,real-time PCR,Western blot and Immunohistochemistry assays showed that mRNA and protein expressions of ELA and APJ receptors were also decreased in placental tissues of late-onset PE.In addition,our in vitro studies showed that the addition of exogenous ELA significantly improved the invasion ability and proliferation ability of trophoblast cells,and this function was inhibited by APJ specific antagonist ML221 and APJ siRNA.These data suggest that ELA/APJ system may play an important role in the pathogenesis of late-onset PE and ELA may be a biological marker for the diagnosis of late-onset PE.