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

OBJECTIVES: Preeclampsia is primarily a disorder of the maternal endotheliu m. An as yet unidentified circulating factor causes widespread alteration i n endothelial function, and levels of vascular endothelial growth factor ar e elevated in preeclampsia. We hypothesized that vascular endothelial growt h 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 i n vitro. These cultured cells were then stimulated with vascular endothelia l growth factor and with plasma from women with preeclampsia in the presenc e and absence of anti-vascular endothelial growth factor antibody. Prostacy clin, nitric oxide, and lactate dehydrogenase levels were measured. RESULTS: Vascular endothelial growth factor induced a significant concentra tion-dependent increase in prostacyclin production but not nitric oxide pro duction. Cells stimulated with plasma from women with preeclampsia showed i ncreases in production of both prostacyclin and nitric oxide. Vascular endo thelial growth factor concentration in plasma was correlated with prostacyc lin production by stimulated cells. The increase in prostacyclin production that usually followed the addition of plasma did not occur when anti-vascu lar endothelial growth factor antibody was present. CONCLUSIONS: Vascular endothelial growth factor has the ability to alter en dothelial cell function in a manner analogous to that of plasma from women with preeclampsia.