Low-molecular Weight Heparin Induces In Vitro Trophoblast Invasiveness: Role of Matrix Metalloproteinases and Tissue Inhibitors

Nicoletta Di Simone, Fiorella Di Nicuolo, Maurizio Sanguinetti, Sergio Ferrazzani, Maria Clara D'Alessio, Roberta Castellani, Adriano Bompiani, Alessandro Caruso

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

69 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)298-304
Numero di pagine7
RivistaPlacenta
DOI
Stato di pubblicazionePubblicato - 2007

Keywords

  • Heparin
  • Metalloproteinase
  • Pregnancy
  • Trophoblast

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