tailieunhanh - Báo cáo hóa học: "Evaluation of the anti-angiogenic properties of the new selective aVb3 integrin antagonist RGDechiHCit"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Evaluation of the anti-angiogenic properties of the new selective aVb3 integrin antagonist RGDechiHCit | Santulli et al. Journal of Translational Medicine 2011 9 7 http content 9 1 7 TRANSLATIONAL MEDICINE RESEARCH Open Access Evaluation of the anti-angiogenic properties of the new selective avP3 integrin antagonist RGDechiHCit 1 1 2 11 Gaetano Santulli Maria Felicia Basilicata Mariarosaria De Simone Carmine Del Giudice Antonio Anastasio Ch - I Z-J - c rri s Fz S 1 It I I - k Z-J z- z 3 A M l A I s FFz 4 D r I I z I z I V V I rr r 1 VI z Dz z l r r s2 I I I r ĩ Z Z I rev4 Daniela Sorriento Michele Saviano Annarita Del Gatto Bruno Trimarco Carlo Pedone Laura Zaccaro Guido Iaccarino1 Abstract Background Integrins are heterodimeric receptors that play a critical role in cell-cell and cell-matrix adhesion processes. Among them aVp3 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 aVp3 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 avP3 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 .