Academic Journals Database
Disseminating quality controlled scientific knowledge

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

Author(s): Santulli Gaetano | Basilicata Maria | De Simone Mariarosaria | Del Giudice Carmine | Anastasio Antonio | Sorriento Daniela | Saviano Michele | Del Gatto Annarita | Trimarco Bruno | Pedone Carlo | Zaccaro Laura | Iaccarino Guido

Journal: Journal of Translational Medicine
ISSN 1479-5876

Volume: 9;
Issue: 1;
Start page: 7;
Date: 2011;
Original page

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.
     40% off discount for PC Health Advisor