Abstract
Background: Gene therapy in cardiovascular disease promises to be of great impact. The ideal
vector for the therapeutic gene transfection remains to be determined. The aim of
the present study was to investigate the efficacy of gene transfer using adeno-associated
virus vectors carrying the lacZ-reporter gene (AAV-lacZ) in a previously described
coronary recirculation model. Methods: Beating Lewis rat hearts perfused with oxygenated Krebs-Henseleit solution were harvested,
after which an atrial septal defect (ASD) was created. All vessels were tied, and
AAV-lacZ was injected into the aortic root. The solution was recirculated through
the ASD to the left side of the heart and pumped back to the coronary arteries by
the left ventricle. Incubation was allowed for 20 min at 15° C, and the hearts were
subsequently transplanted heterotopically in syngeneic rats. Three increasing doses
(109, 1010, 1011 e. u.) of AAV-lacZ virus vectors were used to study the rate of gene
transfer. All hearts were harvested after 7 - 60 days and evaluated histologically
for expression of the lacZ-gene. Results: Dose-dependent gene transfer was observed. Even after 60 days, there was no obvious
decline in gene expression. Conclusion: Adeno-associated virus vectors offer effective and uniform gene transfer in the myocardium
after transcoronary injection and recirculation. Due to the lack of immune response
previously described, no decrease in gene expression can be observed up to 60 days
after injection.
Key words
Gene therapy - cardiovascular gene transfer - Adeno-associated virus vectors
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Priv. Doz. Dr. Boulos Asfour
Department of Thoracic and Cardiovascular Surgery, University of Muenster
Albert-Schweitzer Straße 33
48129 Münster
Germany
Phone: +49 (251) 834-74 01/74 06
Fax: +49 (251) 834-83 16
Email: asfour@uni-muenster.de
