Sarosh Rana

Chapter 6 – Angiogenesis and Preeclampsia

This chapter reviews placental angiogenesis, the process of neovascularization from preexisting blood vessels, and vasculogenesis, the process of blood vessel generation from angioblast precursor cells, in relation to preeclampsia. The developing human placenta undergoes extensive angiogenesis and vasculogenesis, and also undergoes a process of vascular mimicry (also referred to as pseudovasculogenesis) as cytotrophoblasts convert from an epithelial to an endothelial phenotype. Failure of placental angiogenesis and pseudovasculogenesis during early development has been linked to the pathogenesis of preeclampsia. Placentas in preeclamptic subjects produce an excess of antiangiogenic factors (e.g., soluble fms-like tyrosine kinase-1 and soluble endoglin) that enter the maternal circulation and impair vascular endothelial cell signaling of proangiogenic factors such as vascular endothelial growth factor and placental growth factor. We also discuss evidence that measurement of circulating angiogenic factors in the plasma more accurately reflects the morbidity of severe disease and the risk of adverse outcomes related to preeclampsia. In addition, the mechanisms as to how antiangiogenic proteins cause preeclamptic and eclamptic signs and symptoms are extensively reviewed, and the implications of these findings for preventive or curative therapies are noted.