Induction of reverse remodeling via reconstruction of action potential by transplantation of Kv1.3 transfected fibloblast in failured heart.

通过在衰竭心脏中移植 Kv1.3 转染的成纤维细胞来重建动作电位来诱导逆重塑。

• 批准号: 23591061
• 负责人: NIWANO Shinichi
• 金额: $ 3.33万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591061/
• 关键词: Kv1.3; Kir2.1; 電気的リモデリング; 構造的リモデリング; 心不全; 不整脈

The down-regulation of Ito channel in failure heart will prolong the action potential duration and it accelerates the calcium over-load induced myocardial injury. This study aimed to induce reverse remodeling by removing this vicious circle via normalization of action potential. In our preceding study, we tried to transfect Ito channel directly to the myocyte by using Kv4.2, Kv4.3 and KChIP2 transfection, but enough amount of expression of these molecules myocyte could not be achieved, then we utilized fibroblast transplantation method in this study. We transfected Kv1.3+Kir2.1 into the fibroblast, then tried to transplant them into cardiac tissue. They will construct electrical connection to the myocytes and the action potential will be shortened as well as decrease in calcium over-load in the failure myocytes. In the recent protocol, we succeeded to transfect Kv1.3 to the fibroblast but the stable expression of Kir2.1 was not achieved during the scheduled study period.

ITO通道在失败心脏中的下调将延长动作电位持续时间，并加速钙过负荷会诱导的心肌损伤。这项研究旨在通过归一化动作电位去除这种恶性循环来诱导反向重塑。在上一项研究中，我们试图通过使用KV4.2，KV4.3和K​​CHIP2转染将ITO通道直接转染到心肌细胞，但是无法实现这些分子的足够表达，因此我们在这项研究中利用了成纤维细胞移植方法。我们将KV1.3+KIR2.1转染到成纤维细胞中，然后试图将其移植到心脏组织中。它们将构建与肌细胞的电连接，并将缩短动作电位，并减少衰竭肌细胞中钙的载荷。在最近的协议中，我们成功地将KV1.3转染至成纤维细胞，但是在预定的研究期间未实现Kir2.1的稳定表达。

项目成果

Angiotensin II-mediated Up-regulation of Connective Tissue Growth Factor (CTGF) Promotes Atrial Tissue Fibrosis in the Canine Atrial Fibrillation Model.

血管紧张素 II 介导的结缔组织生长因子 (CTGF) 上调促进犬心房颤动模型中的心房组织纤维化。

• 发表时间: 2012
• 期刊: EUROPACE
• 影响因子: 6.1
• 作者: Kiryu M;Niwano S;Niwano H,et al.
• 通讯作者: Niwano H,et al.

Electrical Remodeling Induced by Primary Oxidative Stress-Studies in Primary Hyperoxidative Mice Model.

原发性氧化应激诱导的电重塑——原发性高氧化小鼠模型研究。

• 作者: Tanaka F;Makita S;Onoda T;Tanno K;Ohsawa M;Itai K;Sakata K;Omama S;Yoshida Y;Ogasawara K;Ogawa A;Ishibashi Y;Kuribayashi T;Okayama A;and Nakamura M;Niwano S
• 通讯作者: Niwano S

Electrical Remodeling Induced by Primary Oxidative Stress-Studies in Primary Hyperoxidative Mice Model

原发性氧化应激诱导的电重塑——原发性高氧化小鼠模型研究

• 发表时间: 2013
• 作者: Nakamura M;Koeda Y;Tanaka F;Onoda T;Itai K;Ohsawa M;Tanno K;Sakata K;Omama S;Ishibashi Y;Makita S;Ohta M;Ogasawara K;Komatsu T;Okayama A.;馬場彰泰;Niwano S
• 通讯作者: Niwano S