Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration

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.