Preeclampsia and the Anti-Angiogenic State

Abstract

Preeclampsia is a major cause of maternal and fetal morbidity and mortality worldwide, however, its etiology remains unclear. Abnormal placental angiogenesis during pregnancy resulting from high levels of anti-angiogenic factors, soluble Flt1 (sFlt1) and soluble endoglin (sEng), has been implicated in preeclampsia pathogenesis. Accumulating evidence also points to a role for these anti-angiogenic proteins as serum biomarkers for the clinical diagnosis and prediction of preeclampsia. Uncovering the mechanisms of altered angiogenic factors in preeclampsia may also provide insights into novel preventive and therapeutic options.

Figure 1. sFlt1 and sEng Causes Endothelial Dysfunction by Antagonizing VEGF and TGF-β1 signaling

There is mounting evidence that VEGF and TGF-β1 are required to maintain endothelial health in several tissues including the kidney and perhaps the placenta. During normal pregnancy, vascular homeostasis is maintained by physiological levels of VEGF and TGF-β1 signaling in the vasculature. In preeclampsia, excess placental secretion of sFlt1 and sEng (two endogenous circulating anti-angiogenic proteins) inhibits VEGF and TGF-β1 signaling respectively in the vasculature. This results in endothelial cell dysfunction, including decreased prostacyclin, nitric oxide production and release of procoagulant proteins. Figure reproduced with permission from Karumanchi et al.