A novel gene therapy for congestive heart failure.
一种治疗充血性心力衰竭的新型基因疗法。
基本信息
- 批准号:08557079
- 负责人:
- 金额:$ 10.62万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (A)
- 财政年份:1996
- 资助国家:日本
- 起止时间:1996 至 1997
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Beta adrenergic receptor system has a major important role in cardiac contraction. If the receptor can be increased by exogenous administration in the hearts in which the receptor is downregulated, this approach may improve the cardiac function. To test whether in-vivo gene transfection of beta 2 adrenergic receptor (B2AR) into the normal and the failing heart by constriction of the abdominal aorta can enhance cardiac function, we transfected with cDNA of the receptor in the heart of Sprague-Dawley rat by intracoronary infusion of hemaagglutinating virus of Japan (HVJ) -liposome plasmid complex including human B2AR gene (BAR (+) and pBAR (+) group). Control hearts were infused with HVJ-liposome plasmid complex without the receptor gene (BAR (-) and pBAR (-) group). Four days after transfection, the hearts were examined. Immunohistochemical labeling using specific antibody to human B2AR demonstrated that the sarcolemma of the myocytes in BAR (+) and pBAR (+) groups was well labeled, while anywhere in BAR (-) and pBAR (-) groups was not. Ligand binding assay using [125I] -cyanopindolol revealed that the receptor density of the hearts in BAR (+) and pBAR (+) groups was significantly higher than in BAR (-) and pBAR (-) groups. Evaluation using Langendorff system demonstrated that developed pressure and maximum derivative of the left ventricle after infusion of isoproterenol were significantly higher in BAR (+) and pBAR (+) groups than in BAR(-) and pBAR (-) groups. Minimum derivative of the left ventricle after infusion of isoproterenol was significantly lower in BAR (+) and pBAR (+) groups than in BAR (-) and pBAR (-) groups. Our results indicated that beta 2 adrenergic receptor was overexpressed approximately 4 times in normal rat hearts and the failing heart by pressure overload by in-vivo gene transfection using HVJ liposome method and the transfected hearts demonstrated marked enhancements in cardiac response after infusion of isoproterenol.
肾上腺素能受体系统在心脏收缩中起着重要的作用。如果受体下调的心脏可以通过外源性给药增加受体,这种方法可能改善心功能。为了检验通过腹主动脉收缩将β 2肾上腺素能受体(B2AR)基因转染正常和衰竭心脏是否能增强心功能,我们采用冠状动脉内灌注日本凝血病毒(HVJ) -含人B2AR基因的脂质体复合物转染了Sprague-Dawley大鼠心脏的受体cDNA (BAR(+)组和pBAR(+)组)。对照心脏输注不含受体基因的hvj脂质体复合物(BAR(-)组和pBAR(-)组)。转染4天后,检查心脏。人B2AR特异性抗体免疫组化标记显示BAR(+)和pBAR(+)组肌细胞肌膜标记良好,而BAR(-)和pBAR(-)组肌细胞肌膜未标记。[125I] -cyanopindolol配体结合分析显示,BAR(+)和pBAR(+)组心脏受体密度显著高于BAR(-)和pBAR(-)组。Langendorff系统评价显示,异丙肾上腺素输注后,BAR(+)和pBAR(+)组左心室发育压力和最大导数显著高于BAR(-)和pBAR(-)组。异丙肾上腺素输注后,BAR(+)和pBAR(+)组左心室最小导数显著低于BAR(-)和pBAR(-)组。结果表明,HVJ脂质体法转染β 2肾上腺素能受体在正常大鼠心脏和压力过载衰竭心脏中过表达约4倍,转染后的心脏在输注异丙肾上腺素后心脏反应明显增强。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Sawa Y,: "A novel strategy for myocardial protection using in vivo transfection of cis element ´decoy´ against NFkB binding site." Circulation,. 96(Suppl II). II-280-II-285 (1997)
Sawa Y,:“利用针对 NFkB 结合位点的顺式元件‘诱饵’体内转染的心肌保护新策略。”,Circulation,96(增刊 II)(1997 年)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Sawa Y, Kaneda Y, Matsuda H, et al.: "Effcient gene transfer method into the whole heart through the coronary artery with Hemaggulutinating virus of Japan liposome." J.Thorac.Cardiovasc.Surg.,. 113(3). 512-519 (1997)
Sawa Y、Kaneda Y、Matsuda H 等人:“利用日本脂质体血凝病毒通过冠状动脉将基因有效转移到整个心脏的方法。”
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- 发表时间:
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- 影响因子:0
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Suzuki K,: "In vivo gene transfection with Heat Shock Protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat." J.Clin.Invest.,. 99(7). 1645-1650 (1997)
Suzuki K,:“热休克蛋白 70 的体内基因转染增强了大鼠心肌对缺血再灌注损伤的耐受性。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Sawa Y,Kaneda Y,Matsuda H,et al.: "Efficient gene transfer method into the whole heart through the coronary artery with Hemaggulutinating virus of Japan liposome." J.Thorac.Cardiovasc.Surg.113 (3). 512-519 (1997)
Sawa Y,Kaneda Y,Matsuda H,等人:“利用日本脂质体血凝病毒通过冠状动脉将基因有效转移到整个心脏的方法。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Suzuki K,Sawa Y,Kaneda Y,Matsuda H,at al.: "In vivo gene transfection with Heat Shock Protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat." J.Clin.Invest.99 (7). 1645-1650 (1997)
Suzuki K、Sawa Y、Kaneda Y、Matsuda H 等人:“用热休克蛋白 70 进行体内基因转染可增强大鼠心肌对缺血再灌注损伤的耐受性。”
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- 影响因子:0
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MATSUDA Hikaru其他文献
MATSUDA Hikaru的其他文献
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{{ truncateString('MATSUDA Hikaru', 18)}}的其他基金
Introduction of new strategy for end-stage heart failure by implantable ventricular assist device aiming to long-term-support with reintegration into society : Survey for the background and possible candidates.
通过植入式心室辅助装置引入治疗终末期心力衰竭的新策略,旨在为重新融入社会提供长期支持:调查背景和可能的候选人。
- 批准号:
21390396 - 财政年份:2009
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Myocardial regeneration therapy using nanotechnology enhances self-regeneration in damaged myocardium
使用纳米技术的心肌再生疗法可增强受损心肌的自我再生
- 批准号:
15209046 - 财政年份:2003
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
STUDIES FOR ESTABLISHMENT OF PEDIATRIC HEART AND LUNG TRANSPLANTATION IN JAPAN
日本开展儿科心肺移植的研究
- 批准号:
12307027 - 财政年份:2000
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Researches on novel techniques of organ-selective gene therapy in thoracic surgery
胸外科器官选择性基因治疗新技术研究
- 批准号:
11557100 - 财政年份:1999
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
MULTI-CENTER STUDIES FOR CLINICAL APPLICATION OF PEDIATRIC HEART AND LUNG TRANSPLANTATION IN JAPAN
日本小儿心肺移植临床应用多中心研究
- 批准号:
09307028 - 财政年份:1997
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
A novel myocardial protection with in vivo gene transfection
体内基因转染的新型心肌保护
- 批准号:
06404047 - 财政年份:1994
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Research for natural prognosis and surgical effect in thoracic and abdominal aneurysm
胸腹动脉瘤自然预后及手术效果研究
- 批准号:
04557059 - 财政年份:1993
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
A clinical study on the mechamism and early diagnosis of acute liver dysfunction following cardiac surgery.
心脏术后急性肝功能障碍发生机制及早期诊断的临床研究
- 批准号:
62570636 - 财政年份:1987
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
Assessment of the myocardial protection in critical neonates
危重新生儿心肌保护作用的评估
- 批准号:
60480317 - 财政年份:1985
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
相似海外基金
In vivo transfer of an extracellular domain of platelet-derived growth factor beta gene by HVJ-liposome method ameliorated bleomycin-induced pulmonary fibrosis.
通过 HVJ 脂质体方法体内转移血小板源性生长因子 β 基因的细胞外结构域可改善博莱霉素诱导的肺纤维化。
- 批准号:
08457181 - 财政年份:1996
- 资助金额:
$ 10.62万 - 项目类别:
Grant-in-Aid for Scientific Research (B)