Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling
| Autor: | Robert Doran, Georg D. Duerr, Annika Ottersbach, Wilhelm Roell, Jane Lee, Britta Engelbrecht, Bernd K. Fleischmann, Michael I. Kotlikoff, Miriam Schiffer, Armin Welz, Alexander Pfeifer, Caroline Geisen, Beth Gabris, Guy Salama, Kenichi Kimura, Martin Breitbach, Esther Carls, Ashish Parikh, Katrin Zimmermann, Philipp Sasse, Torsten S. Becker, Alexandra M. Klein, Shaun Reining, Patricia Freitag |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Tachycardia medicine.medical_specialty Science Genetic Vectors Myocardial Infarction Infarction 030204 cardiovascular system & hematology Ventricular tachycardia Nerve conduction velocity Article Myoblasts 03 medical and health sciences Cicatrix Mice 0302 clinical medicine In vivo Internal medicine medicine Myocyte Animals Humans Myocardial infarction cardiovascular diseases Muscle Cells Multidisciplinary business.industry Lentivirus Arrhythmias Cardiac Genetic Therapy Fibroblasts medicine.disease Disease Models Animal 030104 developmental biology HEK293 Cells Connexin 43 Cardiology Tachycardia Ventricular cardiovascular system Myocardial infarction complications Medicine sense organs medicine.symptom business |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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