ELABELA, as a potential diagnostic biomarker of preeclampsia, regulates abnormally shallow placentation via APJ

Abstract

Preeclampsia (PE) is a major cause of maternal mortality and morbidity worldwide. Although there has been great progress in the understanding of PE, the exact cause for the disease development is still unclear. Recently, studies showed that genetic deletion of ELABELA (ELA, also known as APELA) could induce PE-like symptoms in mice. However, the role of ELA in the disease development of PE remains elusive. Our objective was to measure the changes of ELA levels in maternal serum, urine, and placenta from preeclamptic pregnant women and healthy pregnant women and evaluate the correlation between ELA levels and the occurrence of PE. Additionally, we investigated the effect of ELA on the migration and proliferation of human trophoblast cells. ELA levels are significantly decreased in late-onset PE pregnancies compared with normal pregnancies. The mRNA and protein expressions of ELA and the apelin receptor (APLNR or APJ) in late-onset PE placental tissues are also decreased. Furthermore, our in vitro study showed that the addition of ELA significantly increased the invasion ability and proliferation of trophoblast cells, which were inhibited by the APJ-specific antagonist ML221. Our study identified ELA as significantly decreased in late-onset PE; therefore, it might play an important role in the pathogenesis of late-onset PE.

The Elabela-APJ axis: a promising therapeutic target for heart failure

“…Preliminary results show that compared with healthy subjects, circulating levels of ELA are significantly reduced in patients with hypertension [48]. Consistent with this finding, serum levels of ELA are significantly decreased in preeclamptic women [49,50]. These findings support the theory that ELA is an important regulator of BP levels and may bring benefits to HF.…”

“…Underlying mechanisms of the ELA-APJ axis ELA exerts its cardioprotective effects in an APJ receptordependent manner in most studies, although other alternate receptors may exist [4,14,27,50,59]. Ho et al demonstrated that ELA-KO, not apelin-KO, pregnant mice displayed preeclampsia-like symptoms and that infusion of ELA could alleviate these symptoms [65].…”

Circulating RNA Transcriptome of Pregnant Women with TSH Just Above the Trimester-Specific Reference and its Correlation with the Hypertensive Phenotype

“…et al analyzed that an apelin receptor (APLNR) agonist stimulated vasodilation and inotropic actions 41 . Zhou L. et al identified that APLNR showed a decrease in your expression in late-onset preeclampsia placental tissues 42 . This gene was downregulated in GHT; thus, it could be a trigger to the development of preeclampsia in gestational hypothyroidism.…”

Peer Review #1 of "Emerging roles of APLN and APELA in the physiology and pathology of the female reproductive system (v0.1)"

“…Scientists therefore started investigating the change of APELA in PE patients and wanted to know whether the APELA could act as a biomarker (Zhou et al, 2019). In the late-onset PE (LOPE), two studies measured a significant increased concentration of APELA in the placenta and serum (Panaitescu et al, 2020;Para et al, 2020), while one study measured significant decrease (Zhou et al, 2019). And for early-onset PE (EOPE), only one study observed decrease in both APELA mRNA and protein (Wang et al, 2019), while other studies report no significant change of APELA level on either protein or mRNA (Pritchard et al, 2018;Villie et al, 2019;Zhou et al, 2019;Panaitescu et al, 2020;Para et al, 2020).…”

“…In the late-onset PE (LOPE), two studies measured a significant increased concentration of APELA in the placenta and serum (Panaitescu et al, 2020;Para et al, 2020), while one study measured significant decrease (Zhou et al, 2019). And for early-onset PE (EOPE), only one study observed decrease in both APELA mRNA and protein (Wang et al, 2019), while other studies report no significant change of APELA level on either protein or mRNA (Pritchard et al, 2018;Villie et al, 2019;Zhou et al, 2019;Panaitescu et al, 2020;Para et al, 2020). Furthermore, it was found that hypoxia significantly decreased the expression of LIN28B, LIN28A and APELA, and the downregulation of LIN28B and APELA may play a role in PE by reducing trophoblast invasion and syncytialization (Canfield et al, 2019).…”