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.

本研究的目的是建立日本血凝病毒（HVJ）-脂质体基因转移方法及其在心肌保护中的应用。1998年我们成功地将β_2肾上腺素能受体（β_2-adrenergicreceptor，β_2AR）基因和肝细胞生长因子（hepatocyte growth factor，HGF）基因通过冠状动脉内灌注的方法在体内转染到大鼠心脏，并获得了以下证据。1)β 2 AR基因转染肥大大鼠心脏增强异丙肾上腺素的心脏反应2)HGF基因转染缺血-再灌注心脏后，心功能明显恢复（LVDP，max. dp/dt，冠状动脉流量）。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脂质体复合物直接注射到犬缺血心肌中，给药后四周显示局部室壁功能和血流明显恢复。注射肝细胞生长因子的区域毛细血管数量也增加。这些结果为缺血性心脏病的基因治疗提供了可能。

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.

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。

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)