Laser-targeted ablation of the zebrafish embryonic ventricle: A novel model of cardiac injury and repair

Matrone, G., Taylor, J. M. , Wilson, K. S. , Baily, J., Love, G. D., Girkin, J. M., Mullins, J. J., Tucker, C. S. and Denvir, M. A. (2013) Laser-targeted ablation of the zebrafish embryonic ventricle: A novel model of cardiac injury and repair. International Journal of Cardiology, 168(4), pp. 3913-3919. (doi:10.1016/j.ijcard.2013.06.063)

Matrone, G., Taylor, J. M. , Wilson, K. S. , Baily, J., Love, G. D., Girkin, J. M., Mullins, J. J., Tucker, C. S. and Denvir, M. A. (2013) Laser-targeted ablation of the zebrafish embryonic ventricle: A novel model of cardiac injury and repair. International Journal of Cardiology, 168(4), pp. 3913-3919. (doi:10.1016/j.ijcard.2013.06.063)

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Abstract

Background: While the adult zebrafish (Danio rerio) heart demonstrates a remarkable capacity for self-renewal following apical resection little is known about the response to injury in the embryonic heart.<p></p> Methods: Injury to the beating zebrafish embryo heart was induced by laser using a transgenic zebrafish expressing cardiomyocyte specific green fluorescent protein. Changes in ejection fraction (EF), heart rate (HR), and caudal vein blood flow (CVBF) assessed by video capture techniques were assessed at 2, 24 and 48 h post-laser. Change in total and mitotic ventricular cardiomyocyte number following laser injury was also assessed by counting respectively DAPI (VCt) and Phospho-histone H3 (VCm) positive nuclei in isolated hearts using confocal microscopy.<p></p> Results: Laser injury to the ventricle resulted in bradycardia and mild bleeding into the pericardium. At 2 h post-laser injury, there was a significant reduction in cardiac performance in lasered-hearts compared with controls (HR 117 ± 11 vs 167 ± 9 bpm, p ≤ 0.001; EF 14.1 ± 1.8 vs 20.1 ± 1.3%, p ≤ 0.001; CVBF 103 ± 15 vs 316 ± 13μms− 1, p ≤ 0.001, respectively). Isolated hearts showed a significant reduction in VCt at 2 h post-laser compared to controls (195 ± 15 vs 238 ± 15, p ≤ 0.05). Histology showed necrosis and apoptosis (TUNEL assay) at the site of laser injury. At 24 h post-laser cardiac performance and VCt had recovered fully to control levels. Pretreatment with the cell-cycle inhibitor, aphidicolin, significantly inhibited functional recovery of the ventricle accompanied by a significant inhibition of cardiomyocyte proliferation.<p></p> Conclusions: Laser-targeted injury of the zebrafish embryonic heart is a novel and reproducible model of cardiac injury and repair suitable for pharmacological and molecular studies.<p></p>

Item Type:Articles
Additional Information:This work was supported by The British Heart Foundation Centre for Research Excellence Award and the Medical Research Council (UK).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Taylor, Dr Jonathan and Wilson, Dr Kathryn
Authors: Matrone, G., Taylor, J. M., Wilson, K. S., Baily, J., Love, G. D., Girkin, J. M., Mullins, J. J., Tucker, C. S., and Denvir, M. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Science and Engineering > School of Physics and Astronomy
Journal Name:International Journal of Cardiology
Publisher:Elsevier Ireland Ltd.
ISSN:0167-5273
ISSN (Online):1874-1754
Published Online:18 July 2013
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in International Journal of Cardiology 168(4):3913-3919
Publisher Policy:Reproduced under a Creative Commons License

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