title: Antiphospholipid antibodies affect human endometrial angiogenesis: protective effect of a synthetic peptide (TIFI) mimicking the phospholipid binding site of β(2) glycoprotein I.
abstract: OBJECTIVE
  Aim of our study was to investigate whether TIFI, a syntetic peptide able to compete with anti-phospholipid antibodies (aPL) in the binding to endothelium, may restore aPL-inhibited endometrial angiogenesis.
  
  
  METHODS
  The protective role of TIFI was evaluated on: i) aPL-inhibited of human endometrial endothelial cells (HEEC) angiogenesis in vitro; ii) aPL-inhibited vascular endothelial growth factor (VEGF) and metalloproteases (MMPs) expression; iii) aPL-inhibited Nuclear Factor-κB (NF-κB) and Extracellular signal-Regulated Kinase (ERK) activation and (iv) angiogenesis in vivo.
  
  
  RESULTS
  TIFI restores in a dose-dependent manner: i) aPL-mediated inhibition of HEEC angiogenesis in vitro and in vivo (P < 0.05), ii) VEGF (P < 0.001) and MMP-2 (P < 0.05) expression and iii) NF-κB DNA binding and ERK-1/2 activation (P < 0.05) inhibited by aPL.
  
  
  CONCLUSIONS
  Our results show for the first time the protective effects of TIFI, as represented by its ability to interfere with aPL mediated anti-angiogenic activity.
authors: Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors: Nicoletta
authors: N
authors: Di Simone
authors: Silvia
authors: S
authors: D'Ippolito
authors: Riccardo
authors: R
authors: Marana
authors: Fiorella
authors: F
authors: Di Nicuolo
authors: Roberta
authors: R
authors: Castellani
authors: Silvia S
authors: SS
authors: Pierangeli
authors: Pojen
authors: P
authors: Chen
authors: Chiara
authors: C
authors: Tersigni
authors: Giovanni
authors: G
authors: Scambia
authors: Pier Luigi
authors: PL
authors: Meroni
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D019138:Antibodies, Blocking / Q000737:chemistry / Q000494:pharmacology*; D001666:Binding Sites, Antibody / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D004717:Endometrium / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000378:metabolism
chemical_list: D017152:Antibodies, Antiphospholipid; D019138:Antibodies, Blocking; D016328:NF-kappa B; D010455:Peptides; D010743:Phospholipids; C516775:TIFI peptide; D042461:Vascular Endothelial Growth Factor A; D053482:beta 2-Glycoprotein I; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2
keywords: Antiphospholipid antibodies; TIFL; endometrial angiogenesis