Background Integrins are heterodimeric receptors that play a critical role in cell-cell and cell-matrix adhesion processes. Among them, ?V?3 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 ?V?3 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 ?V?3 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.
Evaluation of the anti-angiogenic properties of the new selective alpha(V)beta(3) integrin antagonist RGDechiHCit
De Simone M;Saviano M;Del Gatto A;Pedone C;Zaccaro L;
2011
Abstract
Background Integrins are heterodimeric receptors that play a critical role in cell-cell and cell-matrix adhesion processes. Among them, ?V?3 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 ?V?3 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 ?V?3 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
