Effects of a novel cyclic RGD peptidomimetic on cell proliferation, migration and angiogenic activity in human endothelial cells

• Published in: Vascular cell 2014-05, Vol.6 (1), p.11-11
• Main Authors: Fanelli, Roberto, Schembri, Laura, Piarulli, Umberto, Pinoli, Monica, Rasini, Emanuela, Paolillo, Mayra, Galiazzo, Marisa Carlotta, Cosentino, Marco, Marino, Franca
• Format: Article
• Language: English
• Subjects: Analysis; Angiogenesis; Cell adhesion & migration; Cell growth; Endothelium; Enzyme-linked immunosorbent assay; Experiments; Flow cytometry; Growth factors; Integrins; Kinases; Ligands; Membrane filters; Pharmacology; Phosphorylation; Proteins; RNA; Rodents; Signal transduction; Studies; Vascular endothelial growth factor
• ISSN: 2045-824X; 2045-824X
• DOI: 10.1186/2045-824X-6-11

Cyclic RGD peptidomimetics containing a bifunctional diketopiperazine scaffold are a novel class of high-affinity ligands for the integrins αVβ3 and αVβ5. Since integrins are a promising target for the modulation of normal and pathological angiogenesis, the present study aimed at characterizing the ability of the RGD peptidomimetic cyclo[DKP-RGD] 1 proliferation, migration and network formation in human umbilical vein endothelial cells (HUVEC). Cell viability was assessed by flow cytometry and annexin V (ANX)/propidium iodide (PI) staining. Cell proliferation was evaluated by the ELISA measurement of bromodeoxyuridine (BrdU) incorporation. Network formation by HUVEC cultured in Matrigel-coated plates was evaluated by optical microscopy and image analysis. Integrin subunit mRNA expression was assessed by real time-PCR and Akt phosphorylation by western blot analysis. Cyclo[DKP-RGD] 1 does not affect cell viability and proliferation either in resting conditions or in the presence of the pro-angiogenic growth factors VEGF, EGF, FGF, and IGF-I. Addition of cyclo[DKP-RGD] 1 however significantly decreased network formation induced by pro-angiogenic growth factors or by IL-8. Cyclo[DKP-RGD] 1 did not affect mRNA levels of αV, β3 or β5 integrin subunits, however it significantly reduced the phosphorylation of Akt. Cyclo[DKP-RGD] 1 can be a potential modulator of angiogenesis induced by different growth factors, possibly devoid of the adverse effects of cytotoxic RGD peptidomimetic analogues.