Document Detail

Low-molecular weight heparin induces in vitro trophoblast invasiveness: role of matrix metalloproteinases and tissue inhibitors.
MedLine Citation:
PMID:  16750851     Owner:  NLM     Status:  MEDLINE    
Heparin is used widely for the prevention of pregnancy loss in pregnant women with thrombophilia. However, it is still unknown if heparin may be able to affect trophoblast functions. Therefore, we investigated the hypothesis that low-molecular weight heparin (LMWH) might regulate in vitro trophoblast invasiveness and placental production of matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs). In the first-trimester placental tissue, the MMP-9 expression was observed in both villous and extravillous cytotrophoblast cells, and MMP-2 mainly in villous cytotrophoblast. In human choriocarcinoma cells (JAR), MMP-2 was the dominant form. Heparin significantly enhanced both pro-MMPs and the active forms, and increased Matrigel invasiveness of extravillous trophoblast and choriocarcinoma cells. In choriocarcinoma cells the heparin effect was also indirect, inducing a significant decrease in TIMP-1 and TIMP-2 protein expressions and mRNAs. The present data suggest that the increase in trophoblast invasion by heparin is due to a specific protein playing a role in placental invasion. These observations may help in understanding the effects of heparin treatment during pregnancy.
N Di Simone; F Di Nicuolo; M Sanguinetti; S Ferrazzani; M C D'Alessio; R Castellani; A Bompiani; A Caruso
Publication Detail:
Type:  Journal Article     Date:  2006-06-05
Journal Detail:
Title:  Placenta     Volume:  28     ISSN:  0143-4004     ISO Abbreviation:  Placenta     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-06     Completed Date:  2007-05-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006349     Medline TA:  Placenta     Country:  England    
Other Details:
Languages:  eng     Pagination:  298-304     Citation Subset:  IM    
Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Largo Gemelli 8, 00168 Rome, Italy.
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MeSH Terms
Anticoagulants / pharmacology*
Cell Movement / drug effects
Choriocarcinoma / drug therapy,  enzymology,  pathology
Dose-Response Relationship, Drug
Gene Expression
Heparin, Low-Molecular-Weight / pharmacology*
Matrix Metalloproteinase 2 / genetics,  metabolism
Matrix Metalloproteinase 9 / genetics,  metabolism
Neoplasm Invasiveness
RNA, Messenger / metabolism
Tissue Inhibitor of Metalloproteinase-1 / genetics,  metabolism
Tissue Inhibitor of Metalloproteinase-2 / genetics,  metabolism
Trophoblasts / cytology,  drug effects*,  enzymology
Tumor Cells, Cultured
Reg. No./Substance:
0/Anticoagulants; 0/Heparin, Low-Molecular-Weight; 0/RNA, Messenger; 0/Tissue Inhibitor of Metalloproteinase-1; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC Metalloproteinase 2; EC Metalloproteinase 9

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

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