1. Academic Validation
  2. Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration

Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration

  • J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):284-91. doi: 10.1177/1470320314528364.
Nicola Ferri 1 Federica Panariti 2 Chiara Ricci 2 Giuseppe Maiocchi 3 Alberto Corsini 2
Affiliations

Affiliations

  • 1 Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy nicola.ferri@unimi.it.
  • 2 Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
  • 3 Novartis Farma S.p.A. Medical Department, Origgio, Italy.
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(-7)M) and increasing concentrations of aliskiren (10(-6)-10(-5)M). After 24 h, SMC migration was assessed by Boyden's chamber chemotactic assay using prorenin as chemotactic factor (10(-8)M). The effect of aliskiren on RhoA and Rac activity was also determined by G-LISA assay and the lamellipodia formation by rhodamine-phalloidin staining. Changes in cell morphology were recorded in real-time using the iCelligence system.

Results: Aliskiren determined, at 10(-5)M, a significant inhibition of SMC migration induced by prorenin (-66.4 ± 18.1%; 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.

Keywords

Migration; Rac; prorenin; small GTPases; smooth muscle cells.

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