Document Detail


Sera from preeclampsia patients elicit symptoms of human disease in mice and provide a basis for an in vitro predictive assay.
MedLine Citation:
PMID:  20889559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Early diagnosis and treatment of preeclampsia would significantly reduce maternal and fetal morbidity and mortality. However, its etiology and prediction have remained elusive. Based on the hypothesis that sera from patients with preeclampsia could function as a "blueprint" of causative factors, we describe a serum-based pregnancy-specific mouse model that closely mirrors the human condition as well as an in vitro predictive assay. We show that a single administration of human preeclampsia serum in pregnant IL-10-/- mice induced the full spectrum of preeclampsia-like symptoms, caused hypoxic injury in uteroplacental tissues, and elevated soluble fms-like tyrosine kinase 1 and soluble endoglin, markers thought to be related to the disease. The same serum sample(s) induced a partial preeclampsia phenotype in wild-type mice. Importantly, preeclampsia serum disrupted cross talk between trophoblasts and endothelial cells in an in vitro model of endovascular activity. Disruption of endovascular activity could be documented in serum samples as early as 12 to 14 weeks of gestation from patients who subsequently developed preeclampsia. These results indicate that preeclampsia patient sera can be used to understand the pregnancy-specific disease pathology in mice and can predict the disorder.
Authors:
Satyan Kalkunte; Roland Boij; Wendy Norris; Jennifer Friedman; Zhongbin Lai; Jonathan Kurtis; Kee-Hak Lim; James F Padbury; Leif Matthiesen; Surendra Sharma
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-01
Journal Detail:
Title:  The American journal of pathology     Volume:  177     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2011-03-21     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2387-98     Citation Subset:  AIM; IM    
Affiliation:
Department of Pediatrics, Women and Infants Hospital-Warren Alpert Medical School, Lifespan Center for International Health Research, Brown University, 101 Dudley St, Providence, RI 02905, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia
Biological Assay / methods*
Blood Pressure
Disease Models, Animal*
Female
Gestational Age
Humans
Interleukin-10 / blood,  genetics,  immunology
Kidney / pathology
Mice
Mice, Knockout
Pre-Eclampsia / blood*,  diagnosis*,  immunology
Pregnancy / blood*,  immunology
Serum*
Vascular Endothelial Growth Factor Receptor-1 / blood
Grant Support
ID/Acronym/Agency:
5U01 AI066050/AI/NIAID NIH HHS; P20RR018728/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
130068-27-8/Interleukin-10; EC 2.7.10.1/Flt1 protein, mouse; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1
Comments/Corrections

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