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 > School of Cardiovascular & Metabolic Health |
| 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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