Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats.
Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats.
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DOI：
10.1016/j.ejcts.2004.08.031
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发表时间：
2004-12
期刊：
影响因子：
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通讯作者：
M. Ono;Y. Sawa;N. Fukushima;H. Suhara;Toshikazu Nakamura;C. Yokoyama;T. Tanabe;H. Matsuda
中科院分区：
文献类型：
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作者：
M. Ono;Y. Sawa;N. Fukushima;H. Suhara;Toshikazu Nakamura;C. Yokoyama;T. Tanabe;H. Matsuda
目的：肝细胞生长因子（HGF）是一种多能生长因子，对肺损伤具有抗纤维化作用。本研究探讨了人肝细胞生长因子基因转移是否能减轻肺动脉中膜肥厚和增强前列环素对野百合碱（MCT）诱导的大鼠肺动脉高压的改善作用。方法和结果：在注射MCT前一天，HVJ-脂质体复合物与编码HGF基因的cDNA（H组）、编码PGIS基因的cDNA（P组）、将HGF和PGIS基因（HP组）同时转染到大鼠肝脏作为肺给药系统。对照组（C组）。MCT注射后28天，组织学检查显示肺动脉中壁明显增厚和右心室肥大。对照组外周肺动脉中壁厚度百分比（%WT）、右心室（RV）与左心室（LV）的压力比和RV与LV加间隔的重量比显著增加。与C组相比，H组和HP组的中膜厚度百分比显著改善。P组和HP组RV/LV压力和重量比均较C组明显改善，HP组较P组明显改善。结论：HGF基因转染可减轻MCT大鼠肺动脉中膜肥厚，增强前列环素对肺动脉高压的改善作用。因此，HGF和PGIS的基因治疗可能是一个有前途的策略，严重肺动脉高压。
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.