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

本研究的目的是建立利用日本血凝病毒（HVJ）脂质体技术进行基因转移的方法及其在心脏保护中的应用。1998年，我们通过冠状动脉内灌注成功地将β2 -肾上腺素能受体（β 2ar）基因和肝细胞生长因子（HGF）基因在体内转染到大鼠心脏，获得了以下证据：1) β2AR基因转染肥厚大鼠心脏可增强心脏对异丙肾上腺素的反应。2) HGF基因转染缺血-再灌注心脏后，心肌功能恢复更明显(LVDP, max。Dp /dt（冠状动脉血流）比对照组大。1999年，为了研究人类基因的可能性，我们继续使用犬模型进行实验。我们将HGF基因与hvj -脂质体直接注入犬缺血心肌，给药4周后，局部壁功能和血流明显恢复。HGF注射区毛细血管数量明显增加。这些结果提示了基因治疗缺血性心脏病患者的可能性。

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.