title: Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration.
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.
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy nicola.ferri@unimi.it.
authors: Nicola
authors: N
authors: Ferri
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors: Federica
authors: F
authors: Panariti
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors: Chiara
authors: C
authors: Ricci
authors: Novartis Farma S.p.A. Medical Department, Origgio, Italy.
authors: Giuseppe
authors: G
authors: Maiocchi
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors: Alberto
authors: A
authors: Corsini
mesh_terms: D000577:Amides / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology*; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D012083:Renin / Q000494:pharmacology*; D013997:Time Factors; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000577:Amides; D005650:Fumarates; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C446481:aliskiren; D012083:Renin; D020744:rac GTP-Binding Proteins
keywords: Migration; Rac; prorenin; small GTPases; smooth muscle cells