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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25147-8 |
| _version_ | 1818749374914625536 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T04:02:46Z |
| format | Article |
| id | doaj.art-3cdf27391ef1464998db4351fd85b5c0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:02:46Z |
| publishDate | 2018-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3cdf27391ef1464998db4351fd85b5c02022-12-21T21:21:39ZengNature PortfolioScientific Reports2045-23222018-05-018111410.1038/s41598-018-25147-8Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell couplingWilhelm Roell0Alexandra M. Klein1Martin Breitbach2Torsten S. Becker3Ashish Parikh4Jane Lee5Katrin Zimmermann6Shaun Reining7Beth Gabris8Annika Ottersbach9Robert Doran10Britta Engelbrecht11Miriam Schiffer12Kenichi Kimura13Patricia Freitag14Esther Carls15Caroline Geisen16Georg D. Duerr17Philipp Sasse18Armin Welz19Alexander Pfeifer20Guy Salama21Michael Kotlikoff22Bernd K. Fleischmann23Department of Cardiac Surgery, University of BonnDepartment of Cardiac Surgery, University of BonnInstitute of Physiology I, Life&Brain Center, Medical Faculty, University of BonnInstitute of Physiology I, Life&Brain Center, Medical Faculty, University of BonnDepartment of Medicine, Heart and Vascular Institute and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, School of MedicineDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Pharmacology and Toxicology, Biomedical Center, University of BonnDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Medicine, Heart and Vascular Institute and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, School of MedicineDepartment of Cardiac Surgery, University of BonnDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell UniversityDepartment of Cardiac Surgery, University of BonnDepartment of Cardiac Surgery, University of BonnDepartment of Cardiac Surgery, University of BonnInstitute of Physiology I, Life&Brain Center, Medical Faculty, University of BonnDepartment of Cardiac Surgery, University of BonnInstitute of Physiology I, Life&Brain Center, Medical Faculty, University of BonnDepartment of Cardiac Surgery, University of BonnInstitute of Physiology I, Life&Brain Center, Medical Faculty, University of BonnDepartment of Cardiac Surgery, University of BonnDepartment of Pharmacology and Toxicology, Biomedical Center, University of BonnDepartment of Medicine, Heart and Vascular Institute and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, School of MedicineDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell UniversityInstitute of Physiology I, Life&Brain Center, Medical Faculty, University of BonnAbstract 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.https://doi.org/10.1038/s41598-018-25147-8 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-018-25147-8 |
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