Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration

Nicola Ferri, Federica Panariti, Chiara Ricci, Giuseppe Maiocchi, Alberto Corsini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In the present study, we investigated the potential effect of aliskiren on smooth muscle cell (SMC) migration in response to prorenin. Methods: Cultured human SMCs were incubated with angiotensinogen (ANG) (1.5 10-7M) and increasing concentrations of aliskiren (10-610-5M). After 24 h, SMC migration was assessed by Boydens chamber chemotactic assay using prorenin as chemotactic factor (10-8M). The effect of aliskiren on RhoA and Rac activity was also determined by G-LISA assay and the lamellipodia formation by rhodaminephalloidin staining. Changes in cell morphology were recorded in real-time using the iCelligence system. Results: Aliskiren determined, at 10-5M, a significant inhibition of SMC migration induced by prorenin (-66.418.1%; p > 0.05), while no significant effect was observed when PDGF-BB was utilized as chemotactic agent. Aliskiren also reduced Rac-GTP levels in response to prorenin (-54.2±5.4%) without affecting the RhoA-GTP levels. Finally, aliskiren inhibited both the lamellipodia formation and morphological changes induced by prorenin with no significant effect on PDGF-BB activity. Conclusions: Taken together, we provide the first evidence of the inhibitory action of aliskiren on SMC migration induced by prorenin.

Original languageEnglish
Pages (from-to)284-291
Number of pages8
JournalJRAAS - Journal of the Renin-Angiotensin-Aldosterone System
Volume16
Issue number2
DOIs
Publication statusPublished - Jun 15 2015

Keywords

  • Migration
  • prorenin
  • Rac
  • small GTPases
  • smooth muscle cells

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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