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Inhibition of miR-223 Expression Using a Sponge Strategy Decreases Restenosis in Rat Injured Carotids

Author(s):

Eleonore M’baya-Moutoula, Alexandre Marchand, Isabelle Six, Noura Bahrar, Tanja Celic, Nathalie Mougenot, Pierre Maitrias, Ziad A. Massy, Anne-Marie Lompre, Laurent Metzinger* and Valérie Metzinger-Le Meuth*   Pages 1 - 10 ( 10 )

Abstract:


Objective: Restenosis is a frequent complication of angioplasty. It consists of a neointimal hyperplasia resulting from progression and migration of vascular smooth muscle cells (VSMC) into the vessel lumen. The microRNA miR-223 was recently shown to be involved in cardiovascular diseases including atherosclerosis, vascular calcification and arterial thrombosis. In this study, our aim was to assess the impact of miR-223 modulation on restenosis in a rat model of carotid artery after balloon injury.

Methods: The over and down-expression of miR-223 were induced by adenoviral vectors, containing either a pre-miR-223 sequence allowing artificial miR-223 expression or a sponge sequence, trapping the native microRNA, respectively. Restenosis was quantified on stained rat carotid sections.

Results: In vitro, three mRNA (Myocyte Enhancer Factor 2C (MEF2C), Ras homolog gene family, member B (RhoB) and Nuclear factor 1 A-type (NFIA)) reported as miR-223 direct targets and known to be implicated in VSMC differentiation and contractility were studied by RT-qPCR. Our findings showed that down-expression of miR-223 significantly reduced neointimal hyperplasia by 44% in carotids, and was associated with a 2-3-fold overexpression of MEF2C, RhoB and NFIA in a murine monocyte macrophage cell line, RAW 264.7 cells.

Conclusions: Down-regulating miR-223 could be a potential therapeutic approach to prevent restenosis after angioplasty.

Keywords:

restenosis, microRNA, miR-223, rat carotid, vascular smooth muscle cells

Affiliation:

INSERM U1088, CURS, CHU Amiens Picardie, Avenue René Laënnec, Salouel, F-80054, Amiens, Département des Analyses, Agence Française de Lutte contre le Dopage, 143 avenue Roger Salengro 92290 Châtenay-Malabry, INSERM U1088, CURS, CHU Amiens Picardie, Avenue René Laënnec, Salouel, F-80054, Amiens, INSERM U1088, CURS, CHU Amiens Picardie, Avenue René Laënnec, Salouel, F-80054, Amiens, INSERM U1088, CURS, CHU Amiens Picardie, Avenue René Laënnec, Salouel, F-80054, Amiens, Plateau d’expérimentation Cœur, muscle, vaisseaux IFR 14, Université Pierre et Marie Curie, Paris, INSERM U1088, CURS, CHU Amiens Picardie, Avenue René Laënnec, Salouel, F-80054, Amiens, Division of Nephrology, Ambroise Paré University Hospital, AP-HP, INSERM U1018-Team5-CESP, UVSQ, Boulogne Billancourt/Villejuif, INSERM UMRS 956 Université Pierre et Marie Curie, Institute of Cardiometabolism and Nutrition, Faculté de Médecine, 91 boulevard de l’hôpital, 75634, Paris cedex 13, INSERM U1088, CURS, CHU Amiens Picardie, Avenue René Laënnec, Salouel, F-80054, Amiens, INSERM U1088, CURS, CHU Amiens Picardie, Avenue René Laënnec, Salouel, F-80054, Amiens



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