Effect of Terplex/VEGF-165 gene therapy on left ventricular function and structure following myocardial infarction VEGF gene therapy for myocardial infarction

Background: We used a novel lipopolymeric gene delivery system, TeplexDNA, to transfect myocardium with plasmid vascular endothelial growth factor-165 (pVEGF) and evaluated the ability of pVEGF to preserve left ventricular function and structure after coronary ligation in a rabbit model. Methods: New Zealand white rabbits underwent circumflex coronary ligation after direct intramyocardial injection of either Terplex alone or Terplex+50 mug pVEGF-165. Serial echocardiography and histologic studies were performed (n=12/group). Mortality did not differ between groups. The data is reported as the mean+/-standard deviation. Results: Over the 21 days following coronary ligation, pVEGF-165-treated animals demonstrated significant improvement in fractional shortening (20-25%, p = 0.02), long axis two-dimensional ejection fraction (42-51%, p = 0.02) and short axis m-mode ejection fraction (46-54%, p = 0.02). No significant improvements were noted in the control group. VEGF-treated animals had a 50% increase in peri-infarct vessel density and a trend towards a smaller infarct size (20% vs. 29%, p = 0.10). In animals receiving pVEGF-165, the diastolic ventricular area increased from 1.87+/-0.24 cm(2) prior to ligation to 2.19+/-0.23 cm(2) at 21 days following ligation, compared to an increase from 1.84+/-0.38 to 2.54+/-0.55 cm(2) over the same period in control animals (p = 0.03). Similarly, the systolic ventricular area in VEGF-165 animals increased from 1.06+/-0.26 cm(2) prior to ligation to 1.50+/-0.29 cm(2) at 21 days following ligation, compared to an increase from 1.16+/-0.30 to 1.86+/-0.43 cm(2) over the same period in the control animals (p = 0.04). Conclusion: TerplexDNA mediated delivery of plasmid VEGF administered at the time of coronary occlusion improves left ventricular function and reduces left ventricular dilation following myocardial infarction. (C) 2003 Elsevier B.V All rights reserved.