| Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury. | |
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MedLine Citation:
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PMID: 19234141 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Patricia Redecha; Nico van Rooijen; Donald Torry; Guillermina Girardi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-02-20 |
Journal Detail:
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Title: Blood Volume: 113 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-24 Completed Date: 2009-05-08 Revised Date: 2013-06-02 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 4101-9 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, Weill Medical College at Cornell University, New York, NY, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Abortion, Spontaneous
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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:
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R01 HD036830-08/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anticoagulants; 0/Nitrogen Oxides; 81093-37-0/Pravastatin; 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 |
| Comments/Corrections | |
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