title: 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.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Rome, Italy.
  
  
  METHODS
  Cultures of primary decidual cells isolated from human term placenta.
  
  
  METHODS
  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.
  
  
  METHODS
  Decidual HB-EGF expression/secretion and apoptotic rate induced by TNF-α were investigated.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Both LMWHs induced a significant increase in decidual HB-EGF expression/secretion and reduced TNF-α-induced decidual apoptosis. Tinzaparin demonstrated higher efficacy.
authors.affiliation: Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Rome, Italy. nicolettadisimone@rm.unicatt.it
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Di Simone
authors.forename: Fiorella
authors.initials: F
authors.lastname: Di Nicuolo
authors.forename: Roberta
authors.initials: R
authors.lastname: Castellani
authors.forename: Manuela
authors.initials: M
authors.lastname: Veglia
authors.forename: Chiara
authors.initials: C
authors.lastname: Tersigni
authors.forename: Marco
authors.initials: M
authors.lastname: Silano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tritarelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Riccardo
authors.initials: R
authors.lastname: Marana
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D003656:Decidua / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D017984:Enoxaparin / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D020287:In Situ Nick-End Labeling; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D061251:Primary Cell Culture; D000078222:Tinzaparin; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; C587883:HBEGF protein, human; D006495:Heparin, Low-Molecular-Weight; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D000078222:Tinzaparin; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8