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Sci Rep. 2018 May 8;8(1):7145. doi: 10.1038/s41598-018-25147-8.

Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

Author information

1
Department of Cardiac Surgery, University of Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany. wroell@uni-bonn.de.
2
Department of Cardiac Surgery, University of Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany.
3
Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany.
4
Department of Medicine, Heart and Vascular Institute and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, School of Medicine, 3500 Terrace Street, S368 Scaife Hall, 15261, Pittsburgh, PA, USA.
5
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, T4-018 Veterinary Research Tower, 14853-2703, Ithaca, NY, USA.
6
Department of Pharmacology and Toxicology, Biomedical Center, University of Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany.
7
Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany. bernd.fleischmann@uni-bonn.de.

Abstract

Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45+ cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

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