Preeclampsia: The endothelium, circulating factor(s) and vascular endothelial growth factor

It has been proposed that endothelial cell activation is the primary event in the multisystem disorder of preeclampsia. Evidence for endothelial invol vement in this condition abounds. The best-characterized morphologic abnorm ality of this syndrome, glomerular endotheliosis, involves endothelial cell s. Also associated with preeclampsia is a loss of endothelial cell integrit y, with the consequent increase in vascular permeability, and an increase i n the circulating levels of the endothelial cell markers, fibronectin, von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1. It is now well documented that endothelial activation contribu tes to the coagulation abnormalities observed in this disease. There is muc h evidence that the endothelial alterations in preeclampsia result from one or more circulating factors. The incubation of cultured endothelial cells with serum or plasma samples, taken from normal pregnant women and women wi th preeclampsia, results in marked alterations in cell behavior and metabol ic processes. More recently, experiments employing myographic techniques ha ve demonstrated convincingly the effects of a circulating factor(s) on the function of endothelial cells of resistance arteries. Vascular endothelial growth factor (VEGF) possesses many of the characteristics required of a ca ndidate circulating factor. It contains a hydrophobic secretory signal sequ ence, exerts in vitro effects specific to vascular endothelial cell, and pr omotes endothelial expression of procoagulant activity. Circulating VEGF co ncentrations are elevated in women with preeclampsia, and VEGF increases mi crovascular endothelial cell prostacyclin production in a dose-dependent ma nner, analogues to the acute effects of plasma from patients with preeclamp sia. Similarly, in myographic studies, when myometrial resistance arteries are incubated with VEGF, there are dose-dependent alterations in endotheliu m-dependent behavior, mirroring those found after incubation with plasma fr om patients with preeclampsia. Copyright (C) 1999 by the Society for Gyneco logic Investigation.