Obesity "complements" preeclampsia

Abstract

Preeclampsia (PE) is a devastating adverse outcome of pregnancy. Characterized by maternal hypertension, PE, when left untreated, can result in death of both mother and baby. The cause of PE remains unknown, and there is no way to predict which women will develop PE during pregnancy. The only known treatment is delivery of both the fetus and placenta; therefore, an abnormal placenta is thought to play a causal role. Women with obesity before pregnancy have an increased chance of developing PE. Increased adiposity results in a heightened state of systemic inflammation that can influence placental development. Adipose tissue is a rich source of proinflammatory cytokines and complement proteins, which have been implicated in the pathogenesis of PE by promoting the expression of antiangiogenic factors in the mother. Because an aggravated inflammatory response, angiogenic imbalance, and abnormal placentation are observed in PE, we hypothesize that maternal obesity and complement proteins derived from adipose tissue play an important role in the development of PE.

Keywords: complement; immune; obesity; preeclampsia; pregnancy.

Fig. 1.

Working hypothesis linking maternal obesity and preeclampsia. We hypothesize that excess maternal adipose tissue proximal to the reproductive tract is the source of increased complement components and fragments (C3, Bb, C5a) observed in preeclamptic pregnancies. These complement proteins, found in maternal circulation and placenta, may promote increased production of antiangiogenic factors including soluble fms-like tyrosine kinase (sFlt-1), which in turn, decreases proangiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), creating an angiogenic imbalance. This imbalance results in placental injury, leading to decreased blood flow to the placenta concomitant with alterations in placental cytokines, interleukin (IL)-10 and tumor necrosis factor (TNF)-α, before the presentation of preeclampsia. Yellow circles represent adipocytes. Black circles represent adipose tissue immune cells.