Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model

Objective: We evaluated the potency of therapeutic angiogenesis using intramyocardial injection of naked DNA expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in a porcine myocardial infarction model. Methods: Four weeks after left anterior descending coronary artery ligation, 14 pigs were allocated to pCK-Null (negative control, n = 7) or pCK-HGF-X7 (n = 7) treatment groups. Gated myocardial single photon emission computed tomography was performed 4 and 8 weeks following coronary ligation. The effect of pCK-HGF-X7 on capillary density in the gene-injected myocardium was examined by histological analysis using alkaline phosphatase staining. Results: Segmental myocardial perfusion of the under perfused area (<= 70%) from coronary ligation increased in the pCK-HGF-X7 group (p = 0.051), without significant differences in changes over time between the two groups (p = 0.54). Systolic wall thickening (p = 0.001), left ventricular end-diastolic (p = 0.045) and end-systolic volumes (p = 0.009), and left ventricular ejection fraction (p = 0.041) changed in both groups without significant differences in changes over time between the two groups. The increase in the left stoke volume was higher in the pCK-HGF-X7 group than in the pCK-Null group (p = 0.008). Histological analysis showed that capillary density was significantly higher in the pCK-HGF-X7 group than the pCK-Null group (p < 0.001). Conclusion: Intramyocardial injection of pCK-HGF-X7 induced significant angiogenesis at infarct-border zone, and increased the left ventricular stroke volume probably caused by reverse remodeling process. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.