Molecular Mechanisms of Heat Failure and Its Novel Therapeutic Strategies

热衰竭的分子机制及其新的治疗策略

• 批准号: 12136101
• 负责人: KOMURO Issei
• 金额: $ 21.31万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12136101/
• 关键词: heart failure; angiotensin II; STAT3; bone marrow stem cell; ANP; cardiogenesis; regenerative medicine; 血管新生; ANP; BNP; angiopoietin-1; ErbB; gp130; アンジオテンシンII受容体; エンドセリン; NGF; NRSF; EGF; STAT; 骨髄細胞; 骨髄単核球細胞; CMG細胞; 移植; AT2; GC-A /

Heart failure is a leading cause of death in industrialized nations. Although the mainstay of treatment is pharmacotherapy including treatment with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers, 1-year mortality is nearly 20% even with optimal medical therapy. Because other treatment options such as heart transplantation, ventricular assist devices and artificial hearts are not readily available to most patients, there has been a tremendous need for the development of novel treatment strategies for heart failure. As genetically altered mouse models are valid for investigating heart failure, we analyzed molecular mechanisms of heart failure using the mouse models. Furthermore, we investigated the mechanisms of cardiac regeneration to develop the novel strategies such as gene therapy, cell-based therapy and cytokine therapy.

心力衰竭是工业化国家死亡的主要原因。尽管主要治疗方法是药物治疗，包括血管紧张素转换酶抑制剂、血管紧张素 II 受体阻滞剂和 β 受体阻滞剂治疗，但即使采用最佳药物治疗，1 年死亡率也接近 20%。由于心脏移植、心室辅助装置和人造心脏等其他治疗方案对于大多数患者来说并不容易获得，因此非常需要开发新的心力衰竭治疗策略。由于基因改造的小鼠模型对于研究心力衰竭是有效的，因此我们使用小鼠模型分析了心力衰竭的分子机制。此外，我们研究了心脏再生的机制，以开发新的策略，如基因治疗、细胞治疗和细胞因子治疗。

项目成果

Hosoda T.: "A novel myocyte-specific gene Midori promotes the differentiation of P19CL6 cells into cardiomyocytes"J Biol Chem. 276. 35978-35989 (2001)

Hosoda T.：“一种新型心肌细胞特异性基因 Midori 促进 P19CL6 细胞分化为心肌细胞”J Biol Chem。

Zou Y: "Heat shock transcription factor 1 protects cardiomyocytes from ischemia/reperfusion injury"Circulation. 108. 3024-3030 (2003)

邹宇：“热休克转录因子1保护心肌细胞免受缺血/再灌注损伤”循环。

Funabashi: "Images in cardiovascular medicine. Myocardial fibrosis in fabry disease demonstrated by multislice computed tomography : comparison with biopsy findings."Circulation. 107. 2519-2520 (2003)

Funabashi：“心血管医学图像。多层计算机断层扫描证实法布里病中的心肌纤维化：与活检结果的比较。”循环。

Beating is necessary for transdiffentiation of skeletal muscle-derived cells into cardiomyocytes

搏动对于骨骼肌来源的细胞向心肌细胞的转分化是必要的

• 发表时间: 2003
• 期刊: FASEB J 17
• 作者: Iijima Y;et al.
• 通讯作者: et al.

骨格筋由来の心筋幹細胞

源自骨骼肌的心脏干细胞

• 发表时间: 2004