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

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.