Abstract | BACKGROUND: METHODS AND RESULTS: Twenty-four Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes, and VEGF-165 gene therapy or placebo was administered. A replication-deficient recombinant human adenovirus serotype 5 was used for gene transfer (Ad5-VEGF165). The same viral vector devoid of VEGF gene (Ad5-beta-galactosidase) was used as placebo. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n = 6), IM Ad5-betaGal (n = 6), IC Ad5-VEGF165 (n = 6), and IC Ad5-betaGal (n = 6). All pigs received 5-bromo-2'-deoxyuridine ( BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted at 4 weeks. BrdU-labeled cardiomyocytes in the peri- infarct area were counted by a pathologist blinded to group assignment. The number of BrdU-labeled cardiomyocytes per million cells was 4-fold higher in the group receiving IM VEGF-165 (64 +/- 11.4) vs. IM placebo (16 +/- 10.6), P = 0.034. No difference in infarct size or ventricular function was observed between the groups. CONCLUSIONS: IM VEGF-165 gene therapy promotes cardiomyogenesis in reperfused MI. However, no benefit in infarct size or cardiac function was observed at 4 weeks. The origin of these cells remains unknown and needs to be determined.
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Authors | Mayra Guerrero, Krishna Athota, Jason Moy, Laxmi S Mehta, Ruben Laguens, Alberto Crottogini, Michael Borrelli, Peter Corry, Diane Schoenherr, Ralph Gentry, Judith Boura, Cindy L Grines, Gilbert L Raff, Charles J Shanley, William W O'Neill |
Journal | Journal of interventional cardiology
(J Interv Cardiol)
Vol. 21
Issue 3
Pg. 242-51
(Jun 2008)
ISSN: 0896-4327 [Print] United States |
PMID | 18422517
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
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Topics |
- Adenoviridae
(genetics)
- Animals
- Cell Culture Techniques
- Disease Models, Animal
- Gene Expression
- Genetic Therapy
(methods)
- Genetic Vectors
(therapeutic use)
- Magnetic Resonance Imaging, Cine
- Muscle Development
- Myocardial Infarction
(diagnosis, genetics, therapy)
- Myocardial Reperfusion
- Swine
- Swine, Miniature
- Transduction, Genetic
(methods)
- Vascular Endothelial Growth Factor A
(genetics, therapeutic use)
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