Preeclampsia: multiple approaches for a multifactorial disease - PubMed (original) (raw)
Review
Preeclampsia: multiple approaches for a multifactorial disease
Kathleen A Pennington et al. Dis Model Mech. 2012 Jan.
Abstract
Preeclampsia is a pregnancy-specific disorder characterized by hypertension and excess protein excretion in the urine. It is an important cause of maternal and fetal morbidity and mortality worldwide. The disease is almost exclusive to humans and delivery of the pregnancy continues to be the only effective treatment. The disorder is probably multifactorial, although most cases of preeclampsia are characterized by abnormal maternal uterine vascular remodeling by fetally derived placental trophoblast cells. Numerous in vitro and animal models have been used to study aspects of preeclampsia, the most common being models of placental oxygen dysregulation, abnormal trophoblast invasion, inappropriate maternal vascular damage and anomalous maternal-fetal immune interactions. Investigations into the pathophysiology and treatment of preeclampsia continue to move the field forward, albeit at a frustratingly slow pace. There remains a pressing need for novel approaches, new disease models and innovative investigators to effectively tackle this complex and devastating disorder.
Figures
Fig. 1.
Invasion defects in preeclampsia. (A) In a normal placenta, extravillous cytotrophoblast (ECTB) cells (green) move into the decidua (endometrium) and myometrium via interstitial invasion. Some ECTB cells enter maternal spiral arteries and replace the endothelial cells of the vessel walls, becoming endovascular ECTB (eECTB) cells, increasing vessel compliance and maximizing blood flow into placental blood spaces. (B) In the placenta of a preeclamptic patient, interstitial invasion is shallow and limited, with many ECTB cells in the basal plate remaining attached to anchoring villi (AV). Endovascular invasion is nearly absent, and spiral arterioles remain ‘stiff’. FV, floating villi. Image courtesy of The Curators of the University of Missouri (2011), a public corporation.
Fig. 2.
Factors contributing to the pathophysiology of preeclampsia. The multiple factors that have been proposed to contribute to preeclampsia can be divided into four main categories. Biological models have been used to show that factors in each category contribute to the main symptoms of preeclampsia (hypertension and proteinuria). In addition, these factors influence each other. For example, placental oxygen disruption might impair trophoblast invasion and vice-versa; increased expression of inflammatory cytokines increases expression of anti-angiogenic sFLT-1; autoimmune responses increase placental HIF1α expression; and trophoblast death due to hypoxia might increase autoantibody production.
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