Aim: Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has been found to be involved in the regulation of blood pressure; however, its effects in preeclampsia (PE) and the potential underlying mechanism remain poorly understood. In this study, we aimed to investigate the correlation between ghrelin and PE and reveal the possible mechanism underlying any relationship.
Methods: The levels of ghrelin and VEGF in the plasma of 6 early-onset PE (EOPE), 6 late-onset PE (LOPE) and 12 healthy pregnant (HP) women were detected using enzyme-linked immunosorbent assay (ELISA). The recombinant plasmid, pCDH-ghrelin, was designed to overexpress ghrelin in human umbilical vein endothelial cells (HUVECs). We analyzed angiogenesis in vitro and investigated the mechanism using MTT assay, colony formation assay, transwell migration assay, Matrigel-induced tube formation assay and western blotting.
Results: Ghrelin was significantly decreased in EOPE patients (P < 0.05) but elevated in LOPE patients compared to HP groups (P > 0.05). There was a significant decrease in plasma level of VEGF in EOPE and LOPE patients compared to the controls (P < 0.05). The proliferation, migration and tube formation ability of HUVECs were enhanced after transfection with pCDH-ghrelin. Ghrelin increased VEGF by activating the Jagged1/Notch2 pathway.
Conclusion: Our study uncovered that ghrelin has the potential to improve endothelial function by promoting angiogenesis through Jagged1/Notch2/VEGF pathway.
Keywords: VEGF; angiogenesis; ghrelin; notch pathway; preeclampsia.
© 2020 Japan Society of Obstetrics and Gynecology.