Document Detail


Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury.
MedLine Citation:
PMID:  19234141     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pregnancy loss and intrauterine growth restriction (IUGR) are serious pregnancy complications, and the triggers and mediators of placental and fetal damage are not completely understood. Using a mouse model of recurrent spontaneous miscarriages (DBA/2-mated CBA/J mice) that shares features with human recurrent miscarriage and fetal growth restriction, we identified tissue factor (TF) as an essential participating factor in placental and fetal injury. We have previously shown that C5a releases antiangiogenic molecule sFlt-1 in monocytes that causes defective placental development and fetal death in DBA/2-mated CBA/J mice. In this study, we found that TF not only activates the coagulation pathway, but it also mediates sFlt-1 release in monocytes causing defective placental development and fetal death. Blockade of TF with a monoclonal antibody inhibited sFlt-1 release, prevented the pathological activation of the coagulation pathway, restored placental blood flow, prevented placental oxidative stress, and rescued pregnancies. We also demonstrated that pravastatin, by down-regulating TF expression on monocytes and trophoblasts, prevented placental damage and protected pregnancies in DBA/2-mated CBA/J mice. These studies indicate that TF is an important mediator in fetal death and growth restriction and that statins may be a good treatment for women with recurrent miscarriages and IUGR.
Authors:
Patricia Redecha; Nico van Rooijen; Donald Torry; Guillermina Girardi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-20
Journal Detail:
Title:  Blood     Volume:  113     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-24     Completed Date:  2009-05-08     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4101-9     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Abortion, Spontaneous / metabolism*,  prevention & control*
Animals
Animals, Newborn / injuries,  metabolism
Anticoagulants / pharmacology
Antithrombin III / metabolism
Cells, Cultured
Disease Models, Animal
Female
Humans
Infant, Newborn
Male
Mice
Monocytes / drug effects,  metabolism
Nitrogen Oxides / metabolism
Oxidative Stress
Placenta / blood supply,  metabolism*
Pravastatin / pharmacology*
Pregnancy
Protein Binding
Thrombin / metabolism
Thromboplastin / metabolism*
Trophoblasts / drug effects,  metabolism
Vascular Endothelial Growth Factor Receptor-1 / metabolism
Grant Support
ID/Acronym/Agency:
R01 HD036830/HD/NICHD NIH HHS; R01 HD036830-08/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Nitrogen Oxides; 9000-94-6/Antithrombin III; 9035-58-9/Thromboplastin; EC 2.7.10.1/Flt1 protein, mouse; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1; EC 3.4.21.5/Thrombin; KXO2KT9N0G/Pravastatin
Comments/Corrections

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