Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Epidermal growth factor reduces endothelial dysfunction in primary endothelial cells (#167)

Roxanne Hastie 1 , Stephen Tong 1 , Natalie Hannan 1 , Fiona Brownfoot 1 , Ping Cannon 1 , Tu'uhevaha Kaitu'u-Lino 1
  1. University of Melbourne, Heidelberg, VIC, Australia


Preeclampsia is a serious complication of pregnancy, responsible for both maternal and neonatal morbidity and mortality. Maternal vascular dysfunction is central to its progression and a medical therapeutic that reduces or prevents endothelial dysfunction would be a significant advance in the treatment of preeclampsia. We aim to assess whether Epidermal Growth Factor (EGF), a small endogenous peptide, can reduce endothelial dysfunction in primary human tissues.


Methods and results: We initially confirmed EGF activated the EGFR and down-stream signalling pathways in human umbilical endothelial vein cells (HUVECs) by western blot. We then assessed the effect of EGF on HUVEC proliferation using the xCELLigence system, which allows continuous monitoring of cells in real time. We observed a significant dose-dependent increase in proliferation of HUVECs induced by EGF, with maximal effect observed at 20 ng/ml of EGF. In order to mimic the endothelial dysfunction that occurs in preeclampsia, we treated primary HUVECs with tumor necrosis factor (TNF)-α or serum from preterm preeclamptic women. These increased VCAM-1 and endothelin-1 expression, markers of endothelial dysfunction. This increase in VCAM-1 and endothelin-1 was decreased with the co-administration of EGF, in a dose dependent manner. Given the ability of EGF to reduce cell adhesion molecule VCAM-1, we next assessed its effects on TNFα-induced monocyte adhesion. Primary HUVECs were treated with TNFα inducing significant monocyte adhesion, which was significantly reduced following EGF treatment. Finally we assessed primary HUVEC tube formation in Matrigel, which was significantly disrupted by TNFα, but rescued by co-administration of EGF.

Conclusion: EGF reduces endothelial dysfunction in primary HUVECs. EGF may have potential as a novel peptide treatment for diseases where endothelial dysfunction is present, including preeclampsia.