Adenylate-cyclase VI transforms ventricular cardiomyocytes into biological pacemaker cells

• Verfasst von: Ruhparwar, Arjang [VerfasserIn]
• Verfasst von: Kallenbach, Klaus [VerfasserIn]
• Verfasst von: Klein, Gunnar [VerfasserIn]
• Verfasst von: Bara, Christoph [VerfasserIn]
• Verfasst von: Ghodsizad, Ali [VerfasserIn]
• Verfasst von: Sigg, Daniel C. [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Verfasst von: Haverich, Axel [VerfasserIn]
• Verfasst von: Niehaus, Michael [VerfasserIn]
• Titel: Adenylate-cyclase VI transforms ventricular cardiomyocytes into biological pacemaker cells
• Verf.angabe: Arjang Ruhparwar, Klaus Kallenbach, Gunnar Klein, Christoph Bara, Ali Ghodsizad, Daniel C. Sigg, Matthias Karck, Axel Haverich, and Michael Niehaus
• E-Jahr: 2010
• Jahr: 19 Apr 2010
• Umfang: 6 S.
• Fussnoten: Gesehen am 23.06.2023
• Titel Quelle: Enthalten in: Tissue engineering / A
• Ort Quelle: Larchmont, NY : Liebert, 2008
• Jahr Quelle: 2010
• Band/Heft Quelle: 16(2010), 6, Seite 1867-1872
• ISSN Quelle: 1937-335X
• DOI: doi:10.1089/ten.tea.2009.0537
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1850880808

Abstract

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.