Antiphospholipid antibodies affect human endometrial angiogenesis: protective effect of a synthetic peptide (TIFI) mimicking the phospholipid binding site of β(2) glycoprotein I

Am J Reprod Immunol. 2013 Oct;70(4):299-308. doi: 10.1111/aji.12130. Epub 2013 May 7.

Abstract

Problem: 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.

Conclusion: 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.

Keywords: Antiphospholipid antibodies; TIFL; endometrial angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antiphospholipid / metabolism*
  • Antibodies, Blocking / chemistry
  • Antibodies, Blocking / pharmacology*
  • Binding Sites, Antibody / drug effects
  • Binding, Competitive / drug effects
  • Cells, Cultured
  • Endometrium / blood supply
  • Endometrium / drug effects*
  • Endometrium / immunology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • NF-kappa B / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Physiologic / drug effects
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Phospholipids / metabolism
  • Protein Binding / drug effects
  • Vascular Endothelial Growth Factor A / metabolism
  • beta 2-Glycoprotein I / metabolism

Substances

  • Antibodies, Antiphospholipid
  • Antibodies, Blocking
  • NF-kappa B
  • Peptides
  • Phospholipids
  • TIFI peptide
  • Vascular Endothelial Growth Factor A
  • beta 2-Glycoprotein I
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinase 2