Antiphospholipid Antibodies Affect Human Endometrial Angiogenesis: Protective Effect of a Synthetic Peptide (TIFI) Mimicking the Phospholipid Binding Site of β2glycoprotein I

Authors


Correspondence

Pier Luigi Meroni MD, Division of Rheumatology – Instituto G. Pini, University of Milan, Istituto Auxologico Italiano, Piazza C. Ferrari, 1- 20122 – Milan, Italy.

E-mail: pierluigi.meroni@unimi.it

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.

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