ELABELA improves endothelial cell function via the ELA–APJ axis by activating the PI3K/Akt signalling pathway in HUVECs and EA.hy926 cells

Abstract

Destruction of endothelial cells (ECs) function is involved in the structural and functional pathophysiological processes of preeclampsia (PE). Vascular endothelial injury may pre‐exist for several years in women that develop PE and may pose increased risks for hypertension, coronary artery disease, and type‐2 diabetes mellitus. Previous findings showed that Elabela (ELA), the endogenous ligand of the apelin (APJ) receptor expressed mainly on ECs, may play a protective role in early pregnancy and prevent PE. However, the exact functional role and molecular mechanisms of ELA are unclear. Here, we aimed to classify whether and how ELA improves EC function via the ELA–APJ axis. Two human umbilical vein endothelial cell (HUVEC) lines, namely HUVECs and EA.hy926, were treated with ELA, and then their cellular activities were studied by performing CCK‐8 tests, scratch‐wound analysis, and tube‐formation assays. Doses of ELA exceeding 0.01 μmol/L markedly improved the cell viability, migration, and tube formation ability of HUVECs and EA.hy926 cells. Western blot analysis indicated that the above effects caused by ELA were related to upregulation of the APJ receptor and activation of PI3K/Akt signalling. Further verification tests were performed using the PI3K inhibitor wortmannin, and the results illustrated that inhibiting PI3K/Akt signalling blocked the positive effects of ELA on EC function and APJ receptor expression. Taken together, our findings indicate that ELA may alter EC function via the ELA–APJ axis and PI3K/Akt signalling and that ELA shows promise for use in endothelial dysfunction therapy for preventing and treating PE.

The Role of the Adipokines in the Most Common Gestational Complications

“…The study performed on the population of human umbilical vein endothelial cells revealed that the treatment with ELA solutions improved their viability, migration, and tube formation abilities, which may be beneficial for the patients with features of PE. Those effects were said to be invoked by the upregulation of the APJ expression and the activation of PI3K/Akt pathways [234]. Interestingly it was noted that elabela blood levels, mRNA, and protein expressions in placental tissue are also decreased in patients with late-onset PE [235].…”

Elabela promotes the retinal angiogenesis by inhibiting ferroptosis during the vaso‐obliteration phase in mouse oxygen‐induced retinopathy model

“…Previous studies have reported that ELA could promote angiogenesis in HUVECs, placental development, and cardiovascular diseases. 11,13,25 Herein, we discovered for the first time that early ELA treatment promoted retinal vascular development in vivo, and our result indicated that ELA could rescue retinal vessel loss by reducing the avascular area, increasing the vascular density, and stimulating the growth of tip cells in phase 1 of OIR. In addition, ELA seems to slightly promote the development of retinal vessels in normal mice.…”

The network map of Elabela signaling pathway in physiological and pathological conditions

“…In cell‐based studies, Wang et al have reported that Elabela‐32 significantly improved cell viability, migration, and tube formation ability of human umbilical vein endothelial cell (HUVEC) lines and EA. hy926 cells via the activation of PI3K/AKT signaling (Wang et al 2020). Elabela‐32 treatment of mesenchymal stem cells in a hypoxic/ischemic (H/I) induced rat model demonstrated the improvement of overall cell viability via reduced mitochondrial damage, anti‐apoptosis via enhanced BCL2/BAX expression, and decreased Caspase 3 activity via the PI3K/AKT and MAPK1/3 pathways (Fu et al 2020) (Fig.…”