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 underperfused area (< or =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.