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

Authors:
Gaetano Santulli
Gaetano Santulli
Federico II University of Naples
Italy
Maria Felicia Basilicata
Maria Felicia Basilicata
"Federico II" University of Naples
Italy
Antonio Anastasio
Antonio Anastasio
Department of Clinical Medicine
Italy
Daniela Sorriento
Daniela Sorriento
Department of Clinical Medicine
Italy
Michele Saviano
Michele Saviano
Institute of Biostructures and Bioimaging
Italy

J Transl Med 2011 Jan 13;9. Epub 2011 Jan 13.

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

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.

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http://dx.doi.org/10.1186/1479-5876-9-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027097PMC
January 2011
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