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J Thorac Cardiovasc Surg 2005;130:719-725
© 2005 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Gene transfection of hepatocyte growth factor attenuates the progression of cardiac remodeling in the hypertrophied heart

^a Division of Cardiovascular Surgery, Department of Surgery E1, School of Allied Health Science, Faculty of Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
^b Division of Biochemistry, Department of Oncology, Biomedical Research Center B7, School of Allied Health Science, Faculty of Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
^c Department of Molecular Pathology, School of Allied Health Science, Faculty of Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Received for publication November 21, 2004; revisions received March 11, 2005; accepted for publication April 5, 2005.

^_* Address for reprints: Keiji Iwata, MD, Department of Surgery, Osaka University Graduate School of Medicine (E1), 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan (Email: iwata{at}surg1.med.osaka-u.ac.jp).

OBJECTIVES: Hepatocyte growth factor plays a significant role in angiogenesis, anti-apoptosis, and anti-transforming growth factor-ß1–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-ß1 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-ß1 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-ß1 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.