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 μg 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 cm² 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 cm² 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 cm² prior to ligation to 1.50±0.29 cm² at 21 days following ligation, compared to an increase from 1.16±0.30 to 1.86±0.43 cm² 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.