A new mouse model to explore therapies for preeclampsia.
BACKGROUND
Pre-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.


RESULTS
Here 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
We 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.
Department of Biology, York College, City University of New York, New York, New York, United States of America.
Abdulwahab
A
Ahmed
Jameel
J
Singh
Ysodra
Y
Khan
Surya V
SV
Seshan
Guillermina
G
Girardi
D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D005260:Female; D020738:Leptin / Q000097:blood; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D017035:Pravastatin / Q000008:administration & dosage; D011225:Pre-Eclampsia / Q000503:physiopathology / Q000628:therapy*; D011247:Pregnancy; D011256:Pregnancy Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood
D020738:Leptin; D042461:Vascular Endothelial Growth Factor A; D017035:Pravastatin