Document Detail


Transcriptionally active syncytial aggregates in the maternal circulation may contribute to circulating soluble fms-like tyrosine kinase 1 in preeclampsia.
MedLine Citation:
PMID:  22215706     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cardinal manifestations of the pregnancy-specific disorder preeclampsia, new-onset hypertension, and proteinuria that resolve with placental delivery have been linked to an extracellular protein made by the placenta, soluble fms-like tyrosine kinase 1 (sFlt1), that injures the maternal vasculature. However, the mechanisms by which sFlt1, which is heavily matrix bound, gain access to the systemic circulation remain unclear. Here we report that the preeclamptic placenta's outermost layer, the syncytiotrophoblast, forms abundant "knots" that are enriched with sFlt1 protein. These syncytial knots easily detach from the syncytiotrophoblast, resulting in free, multinucleated aggregates (50-150 μm diameter) that are loaded with sFlt1 protein and mRNA, are metabolically active, and are capable of de novo gene transcription and translation. At least 25% of the measurable sFlt1 in the third-trimester maternal plasma is bound to circulating placental microparticles. We conclude that detachment of syncytial knots from the placenta results in free, transcriptionally active syncytial aggregates that represent an autonomous source of sFlt1 delivery into the maternal circulation. The process of syncytial knot formation, shedding of syncytial aggregates, and appearance of placental microparticles in the maternal circulation appears to be greatly accelerated in preeclampsia and may contribute to the maternal vascular injury that characterizes this disorder.
Authors:
Augustine Rajakumar; Ana Sofia Cerdeira; Sarosh Rana; Zsuzsanna Zsengeller; Lia Edmunds; Arun Jeyabalan; Carl A Hubel; Isaac E Stillman; Samir M Parikh; S Ananth Karumanchi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-03
Journal Detail:
Title:  Hypertension     Volume:  59     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-25     Completed Date:  2012-04-20     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  256-64     Citation Subset:  IM    
Affiliation:
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. arajakum@bidmc.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Cell-Derived Microparticles / pathology*
Cells, Cultured
Female
Humans
Organ Culture Techniques
Placenta / cytology
Pre-Eclampsia / blood*
Pregnancy
Pregnancy Complications, Hematologic / blood*
Pregnancy Proteins / blood
Pregnancy Trimester, Third / blood
RNA, Messenger / blood
Trophoblasts / cytology*
Vascular Endothelial Growth Factor Receptor-1 / blood*
Grant Support
ID/Acronym/Agency:
P01 HD030367/HD/NICHD NIH HHS; R03 HD055219-03/HD/NICHD NIH HHS; R03 HD055219-03/HD/NICHD NIH HHS; UL1 RR024153/RR/NCRR NIH HHS; UL1 TR000005/TR/NCATS NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Pregnancy Proteins; 0/RNA, Messenger; EC 2.7.10.1/FLT1 protein, human; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1
Comments/Corrections
Comment In:
Hypertension. 2012 Feb;59(2):191-3   [PMID:  22215710 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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