Low-molecular-weight heparins induce decidual heparin-binding epidermal growth factor-like growth factor expression and promote survival of decidual cells undergoing apoptosis

Fertil Steril. 2012 Jan;97(1):169-77.e1. doi: 10.1016/j.fertnstert.2011.10.021. Epub 2011 Nov 14.

Abstract

Objective: To evaluate the effects of low-molecular-weight heparins (LMWHs) on decidual heparin-binding epidermal growth factor-like growth factor (HB-EGF) expression/secretion and on TNF-α-induced decidual apoptosis.

Design: Experimental study.

Setting: Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Rome, Italy.

Patient(s): Cultures of primary decidual cells isolated from human term placenta.

Intervention(s): The effects of LMWHs (tinzaparin and enoxaparin) on decidual HB-EGF expression and secretion were investigated by Western blot analysis and ELISA, respectively. TNF-α-induced decidual apoptosis was evaluated by annexin V staining, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay, and caspase activities.

Main outcome measure(s): Decidual HB-EGF expression/secretion and apoptotic rate induced by TNF-α were investigated.

Result(s): Tinzaparin enhanced decidual HB-EGF expression and secretion. TNF-α reduced the number of viable cells by inducing apoptosis. Simultaneous addition of LMWHs (primarily tinzaparin) blocked the increase in annexin V- and TUNEL-positive cells and reduced the amount of caspase activities.

Conclusion(s): Both LMWHs induced a significant increase in decidual HB-EGF expression/secretion and reduced TNF-α-induced decidual apoptosis. Tinzaparin demonstrated higher efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / pharmacology
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Survival / drug effects*
  • Decidua / cytology*
  • Decidua / drug effects*
  • Decidua / metabolism
  • Enoxaparin / pharmacology
  • Female
  • Gene Expression / drug effects
  • Heparin, Low-Molecular-Weight / pharmacology*
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • In Situ Nick-End Labeling
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Pregnancy
  • Primary Cell Culture
  • Tinzaparin
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anticoagulants
  • Enoxaparin
  • HBEGF protein, human
  • Heparin, Low-Molecular-Weight
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Tumor Necrosis Factor-alpha
  • Tinzaparin
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8