Endothelial cell dysfunction

The hypothesis that preeclampsia phenotypes result from endothelial cell dysfunction has been followed by decades of evidence demonstrating vascular dysfunction and augmented vascular reactivity in preeclampsia. Multiple studies have detected biomarkers of endothelial activation prior to overt disease. The concept that endothelial cell dysfunction plays a pathogenetic role in preeclampsia is widely accepted, and investigators are now seeking and identifying circulating mediators of vascular activation. In this chapter, vascular effects of placental microvesicles, leukocytes, cytokines, fatty acids, "antiangiogenic" factors and autoantibodies are reviewed. Also highlighted are theories that oxygen free radicals and other mediators of oxidative stress converge as pathological precursors to endothelial cell dysfunction. Characterization, and ultimate neutralization, of such factors should lead to novel therapeutic strategies to prevent or reduce the severity of preeclampsia.