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Eur Heart J. 2013 Jun;34(22):1636-43. doi: 10.1093/eurheartj/eht105. Epub 2013 Mar 25.

miRNA-21 is dysregulated in response to vein grafting in multiple models and genetic ablation in mice attenuates neointima formation.

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  • 1Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK.

Abstract

AIMS:

The long-term failure of autologous saphenous vein bypass grafts due to neointimal thickening is a major clinical burden. Identifying novel strategies to prevent neointimal thickening is important. Thus, this study aimed to identify microRNAs (miRNAs) that are dysregulated during neointimal formation and determine their pathophysiological relevance following miRNA manipulation.

METHODS AND RESULTS:

We undertook a microarray approach to identify dysregulated miRNAs following engraftment in an interpositional porcine graft model. These profiling experiments identified a number of miRNAs which were dysregulated following engraftment. miR-21 levels were substantially elevated following engraftment and these results were confirmed by quantitative real-time PCR in mouse, pig, and human models of vein graft neointimal formation. Genetic ablation of miR-21 in mice or grafted veins dramatically reduced neointimal formation in a mouse model of vein grafting. Furthermore, pharmacological knockdown of miR-21 in human veins resulted in target gene de-repression and a significant reduction in neointimal formation.

CONCLUSION:

This is the first report demonstrating that miR-21 plays a pathological role in vein graft failure. Furthermore, we also provided evidence that knockdown of miR-21 has therapeutic potential for the prevention of pathological vein graft remodelling.

KEYWORDS:

MicroRNA; Neointimal formation; Vascular remodelling; Vein graft failure

PMID:
23530023
[PubMed - indexed for MEDLINE]
PMCID:
PMC3675389
Free PMC Article
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