Gene Therapy for Angiogenesis under a Ventricular Assist System

Summary

Cardiac regeneration therapy was recently attempted for recovering heart failure. However it is not clear whether the therapy is effective for severe failing hearts that need mechanical circulatory assistance. We examined a gene therapy for angiogenesis after acute myocardial infarction in goats under ventricular assist system (VAS).

Six adult goats (56–65kg) were created with impaired hearts by ligating the coronary artery and installing pulsatile bi-ventricular assist devices (VADs). Hepatocyte Growth Factor (HGF) was selected as a gene for an angiogenesis factor, which also has cardio-protective activities. The HGF group (n=3) were administered 2.0mg human HGF-cDNA plasmid in myocardium. The control group (n=3) were similarly administered beta-galactosidase plasmid. Four weeks after gene transfection, we tried to wean all goats from VADs.

The myocardia transfected with the hHGF-cDNA contained hHGF protein at levels as high as 1.0+/−0.3ng/g tissue 3 days after transfection. After weaning from VADs, the HGF group showed good hemodynamics, while the control group showed deterioration. The percent fractional shortening was significantly higher in the HGF group than the control group (HGF vs. control, 37.9+/−1.7% vs. 26.4+/−0.3%, p<0.01). LV dilatation associated with myocytes hypertrophy and fibrotic changes were detected in the control group, but not in the HGF group. Vascular density was markedly increased in the HGF group.

These results suggest that gene therapy using hHGF may enhance the chance of “bridge to recovery” in the impaired heart under VAS.