The effects of vascular endothelial growth factor on endothelial cells: A potential role in preeclampsia

OBJECTIVES: Preeclampsia is primarily a disorder of the maternal endothelium. An as yet unidentified circulating factor causes widespread alteration in endothelial function, and levels of vascular endothelial growth factor are elevated in preeclampsia. We hypothesized that vascular endothelial growth factor is involved in the alteration of endothelial function and set out to find further evidence for this contention. STUDY DESIGN: Bovine microvascular endothelial cells (B-88) were cultured in vitro. These cultured cells were then stimulated with vascular endothelial growth factor and with plasma from women with preeclampsia in the presence and absence of anti-vascular endothelial growth factor antibody. Prostacyclin, nitric oxide, and lactate dehydrogenase levels were measured. RESULTS: Vascular endothelial growth factor induced a significant concentration-dependent increase in prostacyclin production but not nitric oxide production. Cells stimulated with plasma from women with preeclampsia showed increases in production of both prostacyclin and nitric oxide. Vascular endothelial growth factor concentration in plasma was correlated with prostacyclin production by stimulated cells. The increase in prostacyclin production that usually followed the addition of plasma did not occur when anti-vascular endothelial growth factor antibody was present. CONCLUSIONS: Vascular endothelial growth factor has the ability to alter endothelial cell function in a manner analogous to that of plasma from women with preeclampsia.