Adenylate-cyclase VI transforms ventricular cardiomyocytes into biological pacemaker cells
Introduction: When sinus node or atrioventricular (AV) node cells are damaged by disease, the implantation of an artificial cardiac pacemaker becomes necessary. In search for a biological alternative, the objective of this study was to demonstrate whether in vivo adenoviral gene transfer of Adenylat...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 Apr 2010
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| In: |
Tissue engineering
Year: 2010, Volume: 16, Issue: 6, Pages: 1867-1872 |
| ISSN: | 1937-335X |
| DOI: | 10.1089/ten.tea.2009.0537 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1089/ten.tea.2009.0537 Verlag, lizenzpflichtig, Volltext: https://www.liebertpub.com/doi/10.1089/ten.tea.2009.0537 
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| Author Notes: | Arjang Ruhparwar, Klaus Kallenbach, Gunnar Klein, Christoph Bara, Ali Ghodsizad, Daniel C. Sigg, Matthias Karck, Axel Haverich, and Michael Niehaus |
| Summary: | Introduction: When sinus node or atrioventricular (AV) node cells are damaged by disease, the implantation of an artificial cardiac pacemaker becomes necessary. In search for a biological alternative, the objective of this study was to demonstrate whether in vivo adenoviral gene transfer of Adenylate-Cyclase type VI (AC-VI) can create biological pacemaker activity in a porcine AV node block model. Genetic therapy of arrhythmic disorders of the heart has been subject of extensive studies. Cyclic AMP is generated in response to Beta-adrenergic receptor stimulation and also binds to HCN channels, where it regulates spontaneous rhythmic activity in the sinus node. - - Materials and Methods: Adenoviruses encoding either AC-VI or Beta-Galactosidase (lacZ) gene were injected into the lateral wall of the left ventricle of adult pigs via anterolateral thoracotomy at a dose of 1010 virus particles each. After 12 days, the AV node was ablated and three-dimensional electrophysiological cardiac mapping was performed using the Ensite™ electro-anatomical system. - - Results: After rapid ventricular pacing and administration of Isoprenalin, all animals of the AC-VI group exhibited an escape rhythm originating from the area of the left ventricular injection site at a rate of 100 + 7 beats/min (n = 5), whereas the escape rhythms in the control group (n = 4) originated from the right ventricle. Western blot analysis of the injection sites revealed significantly higher expression of AC-VI in the respective group as compared with the control group. - - Conclusions: Our study demonstrates that AC-VI gene transfer has the potential to create a biological pacemaker system. |
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| Item Description: | Gesehen am 23.06.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1937-335X |
| DOI: | 10.1089/ten.tea.2009.0537 |