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

McDonald, R. A. et al. (2013) miRNA-21 is dysregulated in response to vein grafting in multiple models and genetic ablation in mice attenuates neointima formation. European Heart Journal, 34(22), pp. 1636-1643. (doi: 10.1093/eurheartj/eht105)

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Publisher's URL: http://dx.doi.org/10.1093/eurheartj/eht105

Abstract

<p>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.</p> <p>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 signifi- cant reduction in neointimal formation.</p> <p>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.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robertson, Dr Keith and Baker, Professor Andrew and White, Miss Katie and McDonald, Dr Robert and Kennedy, Professor Simon and Lu, Dr Ruifang and Halliday, Dr Crawford and McClure, Dr John
Authors: McDonald, R. A., White, K. M., Wu, J., Cooley, B. C., Robertson, K. E., Halliday, C. A., McClure, J. D., Francis, S., Lu, R., Kennedy, S., George, S. J., Wan, S., van Rooij, E., and Baker, A. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN:0195-668X
ISSN (Online):1522-9645
Published Online:25 March 2013
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in European Heart Journal
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
583361BHF Chair of Translational Cardiovascular SciencesAndrew BakerBritish Heart Foundation (BHF)CH/11/2/28733RI CARDIOVASCULAR & MEDICAL SCIENCES
519431Interrogation and manipulation of miRNA in acute vascular injuryAndrew BakerBritish Heart Foundation (BHF)RG/09/005/27915RI CARDIOVASCULAR & MEDICAL SCIENCES