Abstract
BackgroundPre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. This syndrome has been known to medical science since ancient times. However, despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment.Methodology/Principal FindingsHere we show that the CBA/J x DBA/2 mouse model of recurrent miscarriage is also a model of immunologically-mediated preeclampsia (PE). DBA/J mated CBA/J females spontaneously develop many features of human PE (primigravidity, albuminuria, endotheliosis, increased sensitivity to angiotensin II and increased plasma leptin levels) that correlates with bad pregnancy outcomes. We previously reported that antagonism of vascular endothelial growth factor (VEGF) signaling by soluble VEGF receptor 1 (sFlt-1) is involved in placental and fetal injury in CBA/J x DBA/2 mice. Using this animal model that recapitulates many of the features of preeclampsia in women, we found that pravastatin restores angiogenic balance, ameliorates glomerular injury, diminishes hypersensitivity to angiotensin II and protects pregnancies.Conclusions/SignificanceWe described a new mouse model of PE, were the relevant key features of human preeclampsia develop spontaneously. The CBA/J x DBA/2 model, that recapitulates this complex disorder, helped us identify pravastatin as a candidate therapy to prevent preeclampsia and its related complications. We recognize that these studies were conducted in mice and that clinical trials are needed to confirm its application to humans.
Highlights
Preeclampsia (PE) is a pregnancy-specific, multisystemic disorder that occurs in about 1 in 12 of all live-birth pregnancies in the United States, and it is a leading cause of maternal and fetal mortality and morbidity [1,2]
The preeclampsia/eclampsia syndrome has been recognized since ancient times
Very little is understood about its etiology and pathophysiology, which are complex and multifactorial
Summary
Preeclampsia (PE) is a pregnancy-specific, multisystemic disorder that occurs in about 1 in 12 of all live-birth pregnancies in the United States, and it is a leading cause of maternal and fetal mortality and morbidity [1,2]. More than 200,000 American women per year develop PE (a number equal to the number of women affected by breast cancer) It is the most common reasons for a woman to die during pregnancy. This syndrome has been known to medical science since ancient times. Despite considerable research, the cause/s of PE remain/s unclear, and there is no effective treatment. Pre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. Despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment
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