Antiphospholipid Antibodies Affect Human Endometrial Angiogenesis: Protective Effect of a Synthetic Peptide (TIFI) Mimicking the Phospholipid Binding Site of beta(2)glycoprotein I

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.