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

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 infar...

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Autores principales:	Wilhelm Roell, Alexandra M. Klein, Martin Breitbach, Torsten S. Becker, Ashish Parikh, Jane Lee, Katrin Zimmermann, Shaun Reining, Beth Gabris, Annika Ottersbach, Robert Doran, Britta Engelbrecht, Miriam Schiffer, Kenichi Kimura, Patricia Freitag, Esther Carls, Caroline Geisen, Georg D. Duerr, Philipp Sasse, Armin Welz, Alexander Pfeifer, Guy Salama, Michael Kotlikoff, Bernd K. Fleischmann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3cdf27391ef1464998db4351fd85b5c0
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spelling	oai:doaj.org-article:3cdf27391ef1464998db4351fd85b5c02021-12-02T12:32:47ZOverexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling10.1038/s41598-018-25147-82045-2322https://doaj.org/article/3cdf27391ef1464998db4351fd85b5c02018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25147-8https://doaj.org/toc/2045-2322Abstract 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.Wilhelm RoellAlexandra M. KleinMartin BreitbachTorsten S. BeckerAshish ParikhJane LeeKatrin ZimmermannShaun ReiningBeth GabrisAnnika OttersbachRobert DoranBritta EngelbrechtMiriam SchifferKenichi KimuraPatricia FreitagEsther CarlsCaroline GeisenGeorg D. DuerrPhilipp SasseArmin WelzAlexander PfeiferGuy SalamaMichael KotlikoffBernd K. FleischmannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wilhelm Roell Alexandra M. Klein Martin Breitbach Torsten S. Becker Ashish Parikh Jane Lee Katrin Zimmermann Shaun Reining Beth Gabris Annika Ottersbach Robert Doran Britta Engelbrecht Miriam Schiffer Kenichi Kimura Patricia Freitag Esther Carls Caroline Geisen Georg D. Duerr Philipp Sasse Armin Welz Alexander Pfeifer Guy Salama Michael Kotlikoff Bernd K. Fleischmann Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling
description	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.
format	article
author	Wilhelm Roell Alexandra M. Klein Martin Breitbach Torsten S. Becker Ashish Parikh Jane Lee Katrin Zimmermann Shaun Reining Beth Gabris Annika Ottersbach Robert Doran Britta Engelbrecht Miriam Schiffer Kenichi Kimura Patricia Freitag Esther Carls Caroline Geisen Georg D. Duerr Philipp Sasse Armin Welz Alexander Pfeifer Guy Salama Michael Kotlikoff Bernd K. Fleischmann
author_facet	Wilhelm Roell Alexandra M. Klein Martin Breitbach Torsten S. Becker Ashish Parikh Jane Lee Katrin Zimmermann Shaun Reining Beth Gabris Annika Ottersbach Robert Doran Britta Engelbrecht Miriam Schiffer Kenichi Kimura Patricia Freitag Esther Carls Caroline Geisen Georg D. Duerr Philipp Sasse Armin Welz Alexander Pfeifer Guy Salama Michael Kotlikoff Bernd K. Fleischmann
author_sort	Wilhelm Roell
title	Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling
title_short	Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling
title_full	Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling
title_fullStr	Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling
title_full_unstemmed	Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling
title_sort	overexpression of cx43 in cells of the myocardial scar: correction of post-infarct arrhythmias through heterotypic cell-cell coupling
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3cdf27391ef1464998db4351fd85b5c0
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Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling

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