title: Evaluation of the anti-angiogenic properties of the new selective αVβ3 integrin antagonist RGDechiHCit.
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.
authors.affiliation: Department of Clinical Medicine, Cardiovascular & Immunologic Sciences, Federico II University of Naples, Italy. guiaccar@unina.it
authors.forename: Gaetano
authors.initials: G
authors.lastname: Santulli
authors.forename: Maria Felicia
authors.initials: MF
authors.lastname: Basilicata
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: De Simone
authors.forename: Carmine
authors.initials: C
authors.lastname: Del Giudice
authors.forename: Antonio
authors.initials: A
authors.lastname: Anastasio
authors.forename: Daniela
authors.initials: D
authors.lastname: Sorriento
authors.forename: Michele
authors.initials: M
authors.lastname: Saviano
authors.forename: Annarita
authors.initials: A
authors.lastname: Del Gatto
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.forename: Carlo
authors.initials: C
authors.lastname: Pedone
authors.forename: Laura
authors.initials: L
authors.lastname: Zaccaro
authors.forename: Guido
authors.initials: G
authors.lastname: Iaccarino
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011921:Rats, Inbred WKY; D013379:Substrate Specificity
chemical_list: D020533:Angiogenesis Inhibitors; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic