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

Capsule:
The effects of tinzaparin and enoxaparin on decidual cells were evaluated. Tinzaparin induced heparinbinding epidermal growth factor–like growth factor expression and secretion. Both low-molecular-weight heparins prevented tumor necrosis factor (TNF) a–induced apoptosis of decidual cells.

Authors:
Nicoletta Di Simone, M.D., Ph.D., Fiorella Di Nicuolo, Ph.D., Roberta Castellani, Manuela Veglia, M.D., Chiara Tersigni, M.D., Marco Silano, M.D., Alessandra Tritarelli, Ph.D., Giovanni Scambia, M.D., Ph.D., Riccardo Marana, M.D.
Volume 97, Issue 1 , Pages 169-177.e1, January 2012

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.

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