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

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Roberto Fanelli Laura Schembri Umberto Piarulli Monica Pinoli Emanuela Rasini Mayra Paolillo Marisa Carlotta Galiazzo Marco Cosentino Franca Marino

Abstract

Background

Cyclic RGD peptidomimetics containing a bifunctional diketopiperazine scaffold are a novel class of high-affinity ligands for the integrins α Vβ 3and α Vβ 5. 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] 1proliferation, migration and network formation in human umbilical vein endothelial cells (HUVEC).

Methods

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.

Results

Cyclo[DKP-RGD] 1does 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] 1however significantly decreased network formation induced by pro-angiogenic growth factors or by IL-8. Cyclo[DKP-RGD] 1did not affect mRNA levels of α V, β 3or β 5integrin subunits, however it significantly reduced the phosphorylation of Akt.

Conclusions

Cyclo[DKP-RGD] 1can be a potential modulator of angiogenesis induced by different growth factors, possibly devoid of the adverse effects of cytotoxic RGD peptidomimetic analogues.

Article Details

How to Cite
FANELLI, Roberto et al. Effects of a novel cyclic RGD peptidomimetic on cell proliferation, migration and angiogenic activity in human endothelial cells. Vascular Cell, [S.l.], v. 6, n. 1, p. 11, may 2014. ISSN 2045-824X. Available at: <https://vascularcell.com/index.php/vc/article/view/10.1186-2045-824X-6-11>. Date accessed: 11 aug. 2022. doi: http://dx.doi.org/10.1186/2045-824X-6-11.
Section
Original Research