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Eur J Cardiothorac Surg 2004;26:1092-1097
© 2004 Elsevier Science NL

Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats

^a Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
^b Division of Molecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
^c Division of Cardiology, Department of Medicine, National Cardiovascular Center, Osaka, Japan

Received 13 April 2004; received in revised form 27 July 2004; accepted 3 August 2004.

^* Corresponding author. Tel.: +81 6 6879 3154; fax: +81 6 6879 3159. (E-mail: sawa{at}surg1.med.osaka-u.ac.jp).

Objective: Hepatocyte growth factor (HGF) is a multi-potent growth factor, which has anti-fibrotic effects for lung injuries. In this study, we investigated whether human HGF gene transfer may attenuate the medial hypertrophy of pulmonary arteries and enhance the ameliorating effect of prostacyclin in monocrotaline (MCT)-induced pulmonary hypertension in rats. Methods and results: The day before MCT injection, HVJ-liposome complex with the cDNA encoding HGF gene (H group), PGIS gene (P group), and both HGF and PGIS gene (HP group) were transfected to the liver of rats as drug delivery system for the lung. Rats transfected with control vector served as controls (C group). Twenty-eight days after MCT injection, histological examination showed marked thickening of medial wall of pulmonary arteries and right ventricular hypertrophy. Percent medial wall thickness (%WT) of peripheral pulmonary arteries, pressure ratio of the right ventricle (RV) to the left ventricle (LV), and weight ratio of the RV to the LV plus septum were significantly increased in the control. Percent medial wall thickness was significantly ameliorated in H group and HP group in comparison with C group. Pressure and weight ratio of RV to LV was significantly ameliorated in P group and HP group in comparison with C group, and was significantly ameliorated in HP group than P group. Conclusions: In vivo gene transfection with HGF gene attenuated the medial hypertrophy of pulmonary arteries and enhanced the ameliorating effect of prostacyclin for pulmonary hypertension in MCT rats. Thus, gene therapy with HGF and PGIS may be a promising strategy for severe pulmonary hypertension.

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