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

Gaetano Santulli, Maria F. Basilicata, Mariarosaria De Simone, Carmine Del Giudice, Antonio Anastasio, Daniela Sorriento, Michele Saviano, Annarita Del Gatto, Bruno Trimarco, Carlo Pedone, Laura Zaccaro, Guido Iaccarino

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number7
JournalJournal of Translational Medicine
Volume9
DOIs
Publication statusPublished - Jan 13 2011

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Endothelial cells
Integrins
Endothelial Cells
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Cell-Matrix Junctions
Inbred WKY Rats
Cell proliferation
Wound Healing
Rats
Tumors
Neoplasms
Animals
Repair
Adhesion
Animal Models
Cells
Cell Proliferation
Tissue

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Santulli, G., Basilicata, M. F., De Simone, M., Del Giudice, C., Anastasio, A., Sorriento, D., ... Iaccarino, G. (2011). Evaluation of the anti-angiogenic properties of the new selective αVβ3 integrin antagonist RGDechiHCit. Journal of Translational Medicine, 9, [7]. https://doi.org/10.1186/1479-5876-9-7

Evaluation of the anti-angiogenic properties of the new selective αVβ3 integrin antagonist RGDechiHCit. / Santulli, Gaetano; Basilicata, Maria F.; De Simone, Mariarosaria; Del Giudice, Carmine; Anastasio, Antonio; Sorriento, Daniela; Saviano, Michele; Del Gatto, Annarita; Trimarco, Bruno; Pedone, Carlo; Zaccaro, Laura; Iaccarino, Guido.

In: Journal of Translational Medicine, Vol. 9, 7, 13.01.2011.

Research output: Contribution to journalArticle

Santulli, G, Basilicata, MF, De Simone, M, Del Giudice, C, Anastasio, A, Sorriento, D, Saviano, M, Del Gatto, A, Trimarco, B, Pedone, C, Zaccaro, L & Iaccarino, G 2011, 'Evaluation of the anti-angiogenic properties of the new selective αVβ3 integrin antagonist RGDechiHCit', Journal of Translational Medicine, vol. 9, 7. https://doi.org/10.1186/1479-5876-9-7
Santulli, Gaetano ; Basilicata, Maria F. ; De Simone, Mariarosaria ; Del Giudice, Carmine ; Anastasio, Antonio ; Sorriento, Daniela ; Saviano, Michele ; Del Gatto, Annarita ; Trimarco, Bruno ; Pedone, Carlo ; Zaccaro, Laura ; Iaccarino, Guido. / Evaluation of the anti-angiogenic properties of the new selective αVβ3 integrin antagonist RGDechiHCit. In: Journal of Translational Medicine. 2011 ; Vol. 9.
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