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Antiphospholipid Antibodies Affect Human Endometrial Angiogenesis: Protective Effect of a Synthetic Peptide (TIFI) Mimicking the Phospholipid Binding Site of β 2 glycoprotein I
Author(s) -
Di Simone Nicoletta,
D'Ippolito Silvia,
Marana Riccardo,
Di Nicuolo Fiorella,
Castellani Roberta,
Pierangeli Silvia S.,
Chen Pojen,
Tersigni Chiara,
Scambia Giovanni,
Meroni Pier Luigi
Publication year - 2013
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12130
Subject(s) - angiogenesis , mapk/erk pathway , in vivo , vascular endothelial growth factor , in vitro , glycoprotein , angiogenin , microbiology and biotechnology , biology , kinase , chemistry , cancer research , biochemistry , vegf receptors
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.