| Targeted inhibition of complement activation prevents features of preeclampsia in mice. | |
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MedLine Citation:
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PMID: 20944547 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Preeclampsia is a major cause of maternal and neonatal morbidity and mortality. In mouse models, complement activation in the placenta is associated with abnormal placental development and miscarriage, and inhibiting complement prevents fetal injury. We mated two mouse strains, DBA/2 and CBA/J, expecting that the pregnancies might show features of preeclampsia and of immunologically mediated pregnancy loss. Along with placental dysfunction, these matings resulted in proteinuria, elevated BUN, fibrin deposition, and glomerular endotheliosis. We blocked placental complement activation throughout pregnancy by administering a single dose of the C3 inhibitor CR2-Crry given on day 5 of the pregnancy. This procedure specifically targets the sites of complement activation without inducing any systemic effects. Placental complement inhibition prevented oxidative stress and placental dysfunction, as well as proteinuria and renal pathologic features of preeclampsia. Thus, local blockade of complement activation at the maternal-fetal interface rescues preeclampsia in mice, and identifies new treatments. Hence, complement triggers a feed-forward cycle of placental damage, antiangiogenic factor production, and maternal vascular damage in patients. |
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Authors:
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Xiaoping Qing; Patricia B Redecha; Melissa A Burmeister; Stephen Tomlinson; Vivette D D'Agati; Robin L Davisson; Jane E Salmon |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-13 |
Journal Detail:
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Title: Kidney international Volume: 79 ISSN: 1523-1755 ISO Abbreviation: Kidney Int. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-13 Completed Date: 2011-05-03 Revised Date: 2012-06-05 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
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Languages: eng Pagination: 331-9 Citation Subset: IM |
Affiliation:
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Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, New York, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Urea Nitrogen Complement Activation / drug effects* Disease Models, Animal Female Fibrin / metabolism Injections, Intravenous Kidney / drug effects*, immunology, metabolism, pathology, physiopathology Mice Mice, Inbred BALB C Mice, Inbred CBA Mice, Inbred DBA Neovascularization, Physiologic / drug effects Oxidative Stress / drug effects Placenta / drug effects*, immunology, metabolism, physiopathology Pre-Eclampsia / drug therapy*, immunology, metabolism, physiopathology Pregnancy Proteinuria / immunology, prevention & control Recombinant Fusion Proteins / administration & dosage* Vascular Endothelial Growth Factor A / administration & dosage Vascular Endothelial Growth Factor Receptor-1 / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI055007/AI/NIAID NIH HHS; HL082485/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CR2-Crry fusion protein, mouse; 0/Recombinant Fusion Proteins; 0/Vascular Endothelial Growth Factor A; 9001-31-4/Fibrin; EC 2.7.10.1/Flt1 protein, mouse; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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