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BioMed Research International - Volume 2015 2015, Article ID 798768, 16 pages -

Review Article

Centre of Excellence for Toxicological Research, Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126 Parma, Italy

Humanitas Clinical and Research Centre, Via Manzoni 56, Rozzano, 20090 Milan, Italy

Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Hammersmith Campus, Imperial College London, Du Cane Road, London W12 0NN, UK

Received 31 December 2014; Revised 27 March 2015; Accepted 30 March 2015

Academic Editor: Rei Shibata

Copyright © 2015 Michele Miragoli and Alexey V. Glukhov. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Atrial fibrillation AF associated with fibrosis is characterized by the appearance of interstitial myofibroblasts. These cells are responsible for the uncontrolled deposition of the extracellular matrix, which pathologically separate cardiomyocyte bundles. The enhanced fibrosis is thought to contribute to arrhythmias “indirectly” because a collagenous septum is a passive substrate for propagation, resulting in impulse conduction block and-or zigzag conduction. However, the emerging results demonstrate that myofibroblasts in vitro also promote arrhythmogenesis due to direct implications upon cardiomyocyte electrophysiology. This electrical interference may be considered beneficial as it resolves any conduction blocks; however, the passive properties of myofibroblasts might cause a delay in impulse propagation, thus promoting AF due to discontinuous slow conduction. Moreover, low-polarized myofibroblasts reduce, via cell-density dependence, the fast driving inward current for cardiac impulse conduction, therefore resulting in arrhythmogenic uniformly slow propagation. Critically, the subsequent reduction in cardiomyocytes resting membrane potential in vitro significantly increases the likelihood of ectopic activity. Myofibroblast densities and the degree of coupling at cellular border zones also impact upon this likelihood. By considering future in vivo studies, which identify myofibroblasts “per se” as a novel targets for cardiac arrhythmias, this review aims to describe the implications of noncardiomyocyte view in the context of AF.





Autor: Michele Miragoli and Alexey V. Glukhov

Fuente: https://www.hindawi.com/



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