Gene transfection with human hepatocyte growth factor complementary DNA plasmids attenuates cardiac remodeling after acute myocardial infarction in goat hearts implanted with ventricular assist devices.
BACKGROUND
Although a left ventricular assist device is often used to provide circulatory support until transplantation in severe heart failure, the mortality of long-term use of left ventricular assist devices remains high. We have shown that hepatocyte growth factor causes angiogenesis, antifibrosis, and antiapoptosis in the myocardium. Therefore, gene therapy with hepatocyte growth factor-complementary DNA plasmids may enhance the chance of "bridge to recovery." In this study, we performed gene therapy with hepatocyte growth factor in the impaired goat heart with a left ventricular assist device.


METHODS
Cardiac impairment was induced in 6 adult goats (56-65 kg) by ligation of the coronary artery, and ventricular assist devices were installed. The hepatocyte growth factor group (HGF; n = 3) was administered human hepatocyte growth factor-complementary DNA plasmid (2.0 mg) in the myocardium. The control group (n = 3) was similarly administered beta-galactosidase plasmid. Four weeks after gene transfection, we attempted to wean all goats from the ventricular assist device.


RESULTS
The myocardia transfected with human hepatocyte growth factor-complementary DNA contained human hepatocyte growth factor protein at levels as high as 1.0 +/- 0.3 ng/g tissue 3 days after transfection. After weaning from the ventricular assist device, the HGF group showed good hemodynamics, whereas the control group showed deterioration. The percentage of 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%, respectively; P < .01). Left ventricular dilatation associated with myocyte hypertrophy and fibrotic changes was detected in the control group but not in the HGF group. Vascular density was markedly increased in the HGF group.


CONCLUSIONS
These results suggest that gene therapy with human hepatocyte growth factor may enhance the chance of bridge to recovery in the impaired heart supported with a ventricular assist device.
Shirakawa
Yukitoshi
Y
Department of Surgery, E1, Division of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Sawa
Yoshiki
Y
Takewa
Yoshiaki
Y
Tatsumi
Eisuke
E
Kaneda
Yasufumi
Y
Taenaka
Yoshiyuki
Y
Matsuda
Hikaru
H
D000818:Animals; D002302:Cardiac Output; D018076:DNA, Complementary / Q000627:therapeutic use*; D015316:Genetic Therapy; D006041:Goats; D006352:Heart Ventricles / Q000473:pathology; D006353:Heart-Assist Devices; D006439:Hemodynamics; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D010957:Plasmids; D014162:Transfection; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D018076:DNA, Complementary; D017228:Hepatocyte Growth Factor