Development of gene therapy to myocardium using transvenous gene transfection method.

本研究的目的是建立日本血凝病毒(HVJ)基因转移方法-脂质体技术及其在心脏保护中的应用。1998年，我们成功地将β2肾上腺素能受体(β2AR)基因和肝细胞生长因子基因导入大鼠心脏，并获得了以下证据。1)将β-2AR基因导入肥厚的大鼠心脏，可增强心脏对异丙肾上腺素的反应。2)转导HGF基因可使缺血再灌注组的心功能明显恢复(LVDP，max)。Dp/dt，冠脉流量)。1999年，为了研究人类基因的可能性，我们继续用犬模型进行实验。我们将复合HGF基因的hvj-脂质体直接注入犬缺血心肌内，给药4周后局部壁功能和血流量明显恢复。HGF注射区毛细血管数量也明显增多。提示对缺血性心脏病患者进行基因治疗是可能的。

The purposes of this research are estabishment of gene transfer method using hemagglutinating virus of Japan(HVJ)-liposome technique and its application to cardioprotection. In 1998 we successfully transfected the β 2-adrenergic receptor(β2AR) gene and the hepatocyte growth factor(HGF)gene in vivo to the rat heart by intracoronary infusion and obtained the following evidence. 1) β2AR gene transfecton to the hypertrophied rat heart enhances the cardiac response to isoproterenol. 2) HGF gene tranfection to the ischemia-reperfusion heart showed more recovery of cardiac function(LVDP, max. dp/dt, coronary flow) than control. In 1999, to examine the possibility of gene for human, we continued experimentation using canine model. We injected HGF gene complexed with HVJ-liposome directly into the canine ishemic myocardium, and showed significant recovery of regional wall function and blood flow four weeks after administration. The number of the capillary vessels was also increased at HGF injected area. These results indicates the possibility of gene therapy to the patients of ischemic heart disease.