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J Am Coll Cardiol, 2000; 35:1323-1330 © 2000 by the American College of Cardiology Foundation |
* Heart Institute Research, Good Samaritan Hospital, Los Angeles, California, USA
Division of Cardiology, University of Southern California, Los Angeles, California, USA
Division of Cardiovascular Research, St. Elisabeth’s Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA
Department of Biochemistry and Molecular Biology, Department of Medicine, University of Southern California, Los Angeles, California, USA
Manuscript received February 4, 1999; revised manuscript received November 5, 1999, accepted December 15, 1999.
Reprint requests and correspondence: Dr. Robert A. Kloner, Heart Institute, Good Samaritan Hospital & Division of Cardiology, University of Southern California, 1225 Wilshire Boulevard, Los Angeles, California 90017-2395
RKloner{at}goodsam.org
OBJECTIVES
The effects of direct intramyocardial injection of the plasmid encoding vascular endothelial growth factor (phVEGF165) in the border zone of myocardial infarct tissue in rat hearts were investigated.
BACKGROUND
Controversy exists concerning the ability of VEGF to induce angiogenesis and enhance coronary flow in the myocardium.
METHODS
Sprague-Dawley rats received a ligation of the left coronary artery to induce myocardial infarction (MI). At 33.1 ± 6.5 days, the rats were injected with phVEGF165 at one location and control plasmid at a second location (500 µg DNA, n = 24) or saline (n = 16). After 33.1 ± 5.7 days, the hearts were excised for macroscopic and histologic analysis. Regional blood flow ratios were measured in 18 rats by radioactive microspheres.
RESULTS
phVEGF165-treated sites showed macroscopic angioma-like structures at the injection site while control DNA and saline injection sites did not. By histology, 21/24 phVEGF165-treated hearts showed increased focal epicardial blood vessel density and angioma-like formation. Quantitative morphometric evaluation in 20 phVEGF165-treated hearts revealed 44.4 ± 10.5 vascular structures per field in phVEGF165-treated hearts versus 21.4 ± 4.7 in control DNA injection sites (p < 0.05). Regional myocardial blood flow ratios between the injection site and noninfarcted area did not demonstrate any difference between phVEGF165-treated hearts (0.9 ± 0.2) and saline-treated hearts (0.7 ± 0.1).
CONCLUSIONS
Injection of DNA for VEGF in the border zone of MI in rat hearts induced angiogenesis. Angioma formation at the injection sites did not appear to contribute to regional myocardial blood flow, which may be a limitation of gene therapy for this application.
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