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 Lompré, Laurent Metzinger*, Valérie Metzinger-Le Meuth*

Journal Name: Current Vascular Pharmacology

Volume 18 , Issue 5 , 2020


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Graphical Abstract:


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. microRNA miR-223 has recently been 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 was 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.

Conclusion: 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, angioplasty.

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Article Details

VOLUME: 18
ISSUE: 5
Year: 2020
Published on: 10 August, 2020
Page: [507 - 516]
Pages: 10
DOI: 10.2174/1570161117666190705141152
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