Melatonin maintains human umbilical vein endothelial cells function through potential regulation of the AKT-mTOR signaling pathway involving SIRT7 in preeclampsia.

INTRODUCTION: Preeclampsia (PE), known for its association with oxidative stress, can lead to impaired endothelial function. Although melatonin, as an antioxidant, has been used for treating PE, the specific mechanism underlying its therapeutic effect remains ambiguous. The aim of this study is to investigate the correlation between melatonin and PE, and explore the mechanism by which melatonin enhances endothelial cell function in PE.

MATERIAL AND METHODS: Serum melatonin levels were quantified by enzyme-linked immunoassay (ELISA), whereas the expression levels of melatonin receptor and sirtuin 7 (SIRT7) in the placental tissues were assessed via western blotting (WB) in both normal and preeclamptic pregnant women. The impact of melatonin on hypoxia-reoxygenation (H/R)-treated wild-type and SIRT7-knockdown human umbilical vein endothelial cells (HUVECs) was evaluated, along with the modulation of SIRT7 expression and the Protein kinase B/mammalian target of rapamycin (AKT/mTOR) signaling pathway.

RESULTS: We observed a reduction in melatonin levels in patients with PE as well as decreased expression of melatonin receptor type 1A (MTNR-1A) and SIRT7 within placenta. Melatonin restored the migration and tube formation abilities and the expression level of SIRT7 in a PE cell model of HUVECs, while this restorative function was abolished upon SIRT7 knockdown. Furthermore, the AKT/mTOR signaling pathway was suppressed following H/R treatment, a phenomenon that was also observed upon SIRT7 knockdown. Conversely, melatonin administration activated the AKT/mTOR signaling pathway.

CONCLUSIONS: Our results indicate a potential correlation between melatonin and the incidence of PE. Melatonin alleviates preeclampsia-related endothelial dysfunction, and this effect is associated with SIRT7 and the AKT/mTOR pathway.