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Evaluation of the anti-angiogenic properties of the new selective αVβ3 integrin antagonist RGDechiHCit

Gaetano Santulli1, Maria Felicia Basilicata1, Mariarosaria De Simone2, Carmine Del Giudice1, Antonio Anastasio1, Daniela Sorriento1, Michele Saviano3, Annarita Del Gatto4, Bruno Trimarco1, Carlo Pedone2, Laura Zaccaro4 and Guido Iaccarino1*

Author Affiliations

1 Department of Clinical Medicine, Cardiovascular & Immunologic Sciences, "Federico II" University of Naples, Italy

2 Department of Biological Sciences, "Federico II" University of Naples, Italy

3 Institute of Crystallography (Consiglio Nazionale delle Ricerche, CNR), Bari, Italy

4 Institute of Biostructures and Bioimaging (Consiglio Nazionale delle Ricerche, CNR), Naples, Italy

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Journal of Translational Medicine 2011, 9:7  doi:10.1186/1479-5876-9-7

Published: 13 January 2011

Abstract

Background

Integrins are heterodimeric receptors that play a critical role in cell-cell and cell-matrix adhesion processes. Among them, αVβ3 integrin, that recognizes the aminoacidic RGD triad, is reported to be involved in angiogenesis, tissue repair and tumor growth. We have recently synthesized a new and selective ligand of αVβ3 receptor, referred to as RGDechiHCit, that contains a cyclic RGD motif and two echistatin moieties.

Methods

The aim of this study is to evaluate in vitro and in vivo the effects of RGDechiHCit. Therefore, we assessed its properties in cellular (endothelial cells [EC], and vascular smooth muscle cells [VSMC]) and animal models (Wistar Kyoto rats and c57Bl/6 mice) of angiogenesis.

Results

In EC, but not VSMC, RGDechiHCit inhibits intracellular mitogenic signaling and cell proliferation. Furthermore, RGDechiHCit blocks the ability of EC to form tubes on Matrigel. In vivo, wound healing is delayed in presence of RGDechiHCit. Similarly, Matrigel plugs demonstrate an antiangiogenic effect of RGDechiHCit.

Conclusions

Our data indicate the importance of RGDechiHCit in the selective inhibition of endothelial αVβ3 integrin in vitro and in vivo. Such inhibition opens new fields of investigation on the mechanisms of angiogenesis, offering clinical implications for treatment of pathophysiological conditions such as cancer, proliferative retinopathy and inflammatory disease.