Document Detail


Targeted inhibition of complement activation prevents features of preeclampsia in mice.
MedLine Citation:
PMID:  20944547     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-13
Journal Detail:
Title:  Kidney international     Volume:  79     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-13     Completed Date:  2011-05-03     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  331-9     Citation Subset:  IM    
Affiliation:
Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
AI055007/AI/NIAID NIH HHS; HL082485/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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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