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

利用静脉基因转染方法开发心肌基因治疗。

• 批准号: 10470273
• 负责人: SAWA Yoshiki
• 金额: $ 8.19万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470273/
• 关键词: GENE TRANSFECTION; MYOCARDIAL PROTECTION; HVJ; 虚血性心疾患; 肝細胞増殖因子; 血管新生; 心不全; β adrenergic receptor; HVJリポソーム法

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.

这项研究的目的是使用日本的血凝结病毒（HVJ） - 脂肪体技术及其在心脏保护中的应用。在1998年，我们通过冠状体内输注成功地将β2-肾上腺素受体（β2AR）基因和体内肝细胞生长因子（HGF）基因转化为大鼠心脏，并获得了以下证据。 1）β2AR基因转染到肥厚的大鼠心脏增强了对异丙肾上腺素的心脏反应。 2）HGF基因转染向缺血 - 重新灌注心脏显示出比对照更多的心脏功能恢复（LVDP，最大DP/DT，冠状动脉流）。 1999年，为了检查人类基因的可能性，我们继续使用犬模型进行实验。我们将与HVJ-脂质体复合的HGF基因直接直接进入犬类等性心肌，并在给药后四周显示区域壁功能和血流的显着恢复。在HGF注射的区域，毛细管vissels的数量也增加。这些结果表明，缺血性心脏病患者基因治疗可能性。

项目成果

Hideki Ueda: "Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart."Ann. Thorac. Surg.. 67. 1726-1731 (1999)

Hideki Ueda：“肝细胞生长因子的基因转染可减轻心脏的再灌注损伤。”Ann。

Youichi Kawahira: "In Vivo Transfer of a β_2Adrenergic Receptor Gene Into the Pressure-Overloaded Rat Heart Enhances Cardiac Response to βAdrenergic Agonis" Circulation. 98. II262-268 (1998)

Youichi Kawahira：“将 β_2 肾上腺素受体基因体内转移至压力超载的大鼠心脏可增强心脏对 β 肾上腺素激动剂的反应”，循环 98。 II262-268 (1998)

Yoichi Kawahira: "Gene transfection of beta 2-adrenegic receptor into the normal rat heart enhances cardiac response to beta-adrenegic agonist"J. Thorac. Cardiovasc. Surg.. 118-3. 446-451 (1999)

Yoichi Kawahira：“将 β2-肾上腺素能受体基因转染至正常大鼠心脏可增强心脏对 β-肾上腺素能激动剂的反应”J.

Yoichi Kawahira: "In vivo transfer of β-adrenegic receptor gene into the pressure-overloaded rat heart enhances cardiac response to β-adrenegic agonist"Circulation. 98. II262-II268 (1998)

Yoichi Kawahira：“将 β-肾上腺素能受体基因体内转移至压力超载的大鼠心脏可增强心脏对 β-肾上腺素能激动剂的反应”，Circulation 98。II262-II268 (1998)

Yoshiki Sawa: "Efficient transfer of oligonucleotides and plasmid DNA into the whole heart through the coronary artery"Gene Therapy. 5. 1472-1480 (1997)

Yoshiki Sawa：“通过冠状动脉将寡核苷酸和质粒DNA有效转移到整个心脏”基因疗法。