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<sup>-7</sup>M) and increasing concentrations of aliskiren (10<sup>-6</sup>10<sup>-5</sup>M). After 24 h, SMC migration was assessed by Boydens chamber chemotactic assay using prorenin as chemotactic factor (10<sup>-8</sup>M). 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<sup>-5</sup>M, 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.
|Titolo:||Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration|
|Parole Chiave:||Migration; small GTPases; smooth muscle cells; prorenin; Rac|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2015|
|Digital Object Identifier (DOI):||10.1177/1470320314528364|
|Appare nelle tipologie:||01 - Articolo su periodico|