Objectives: Hepatocyte growth factor plays a significant role in angiogenesis, anti-apoptosis, and anti-transforming growth factor-beta1-mediated fibrosis in several organs. In this study, we investigated the effect of transfection of the hepatocyte growth factor gene in attenuation of cardiac remodeling in the hypertrophied heart.
Methods: Two weeks after banding the ascending aorta of male Sprague-Dawley rats, a hemagglutinating virus of Japan-liposome complex with (H group) or without (C group) human hepatocyte growth factor cDNA was transfected into the left ventricle wall by direct injection. The hepatocyte growth factor, c-Met, and transforming growth factor-beta1 mRNA levels in the left ventricle were then analyzed by real-time quantitative reverse-transcriptase polymerase chain reaction.
Results: Two weeks after transfection, the expression of transforming growth factor-beta1 mRNA was significantly attenuated in the H group compared with the C group (P < .01). Myocardial collagen content after 4 weeks of banding was significantly lower in the H group (5.0 +/- 0.6 mg/g tissue) than in the C group (7.4 +/- 0.5 mg/g tissue, P < .01). Left ventricular diastolic function (E/A ratios quantified by Doppler echocardiography) showed a significant increase in the H group (1.9 +/- 0.1) compared with the C group (1.1 +/- 0.1, P < .01).
Conclusions: Our results demonstrated that gene transfection of hepatocyte growth factor attenuated left ventricular diastolic dysfunction and cardiac fibrosis in association with a decrease in transforming growth factor-beta1 in the rat heart subjected to pressure overload. Thus, the transfection of the hepatocyte growth factor gene into the hypertrophied heart may be a strategy for the hypertrophied and failing heart even for cardiac surgery.