© 2006 European Society of Cardiology
Angiopoietin-1 for myocardial angiogenesis: A comparison between delivery strategies
a National University Medical Institutes, National University of Singapore Singapore
b Department of Pathology and Laboratory Medicine, Medical Science Building, University of Cincinnati Cincinnati, Ohio 45220, USA
c National Heart Centre, Singapore General Hospital Singapore
d Department of Biological Sciences, National University of Singapore
e Department of Surgery, National University of Singapore and Gleneagles JPMC Cardiac Center Brunei Darussalam
* Corresponding author. Tel.: +1 513 558 2029.
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Abstract |
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We compare the effectiveness of direct adenoviral angiopoietin-1 (Ad-Ang-1) injection with transplantation of skeletal myoblasts (SkMs) over-expressing angiopoietin-1 (Ang-1) for angiogenic response and improvement of heart function in an experimental porcine model of myocardial infarction (MI).
Methods: Ad-Ang-1 was used for intramyocardial injection or transduction of SkMs. Three weeks after coronary artery ligation in 32 female pigs, animals were grouped to receive multiple intramyocardial injections of DMEM without cells (group-1; n=7), or containing 3
108 Lac-z labelled SkMs transduced with Ad-Null vector carrying no gene (group-2; n=7), or 11010 PFU Ad-Ang-1 (group-3; n=9), or 3108 Lac-z labelled SkMs transduced with Ad-Ang-1 (group-4; n=9). The animals were immunosuppressed for 6-weeks. After euthanasia, their heart tissue was processed for histological studies.
Results: Extensive survival of Lac-z positive SkMs was observed in and around the infarct 6 and 12-weeks after transplantation. Fluorescent immunostaining for vWF-VIII at 6-weeks revealed increased blood vessel density (100) in group-4 (p<0.05) as compared with other groups. Regional blood flow (ml/g/min) in the peri-infarct area was improved in group-4 (2.7; p<0.05) as compared with group-1 (1.2±0.1), group-2 (1.1±0.4) and group-3 (1.7±0.1) at 6-weeks. Similarly, ejection fraction was significantly higher in group-4 (49.2±5.9%, p=0.03) as compared with group-1 (36.8±3%) at 6 weeks.
Conclusion: SkMs mediated Ang-1 delivery is associated with improved angiogenic response, regional myocardial perfusion and heart function as compared with direct Ad-Ang-1 administration.
Key Words: Angiopoietin-1 • Angiogenesis • Ischaemia • Myoblast
Received April 27, 2006; Revised July 26, 2006; Accepted October 30, 2006
A part of the data in this paper was presented at the 54th International Congress for European Society of Cardiovascular Surgery, Athens Greece, May 19–22 2005 and awarded the Rabago Prize.