Development of therapies for severe ischemic cardiomyopathy to substute heart transplantation

开发治疗严重缺血性心肌病以替代心脏移植的疗法

• 批准号: 25670390
• 负责人: SATA Masataka
• 金额: $ 2.41万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2013
• 资助国家: 日本
• 起止时间: 2013-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-25670390/
• 关键词: 動脈硬化、; アディポサイトカイン; 脂肪組織; 分子血管病態学; バイパス手術; 心移植; 心筋症; 脂肪移植; 慢性炎症; 動脈硬化; 血行再建

The only effective therapy for ischemic cardiomyopathy is heart transplantation. However, only limited numbers of donors are available in Japan. Therefore, we tried to establish a new strategy to substitute heart transplantation. Histological analysis of human endarterectomy samples and epicardial fat obtained during cardiac bypass surgery revealed enhanced infiltration of inflammatory cells such as macrophages and T cells not only in vessel wall but also in perivascular adipose tissues. We also found that interaction between cell-free DNA released from adipocytes and TLR9 on macrophages plays a crucial role in chronic inflammation in adipose tissues. Based on these observations, we started to develop a new surgical strategy to treat patients with ischemic cardiomyopathy by reconstructing coronary artery with exogenous artery and subcutaneous adipose tissues.

缺血性心肌病的唯一有效治疗方法是心脏移植。然而，在日本，只有有限数量的捐助者。因此，我们试图建立一种新的替代心脏移植的策略。对心脏搭桥手术期间获得的人动脉内膜切除术样品和心外膜脂肪的组织学分析显示，不仅在血管壁中而且在血管周围脂肪组织中，炎性细胞如巨噬细胞和T细胞的浸润增强。我们还发现，从脂肪细胞释放的游离DNA与巨噬细胞上的TLR9之间的相互作用在脂肪组织的慢性炎症中起着至关重要的作用。基于这些观察，我们开始开发一种新的外科策略，通过用外源性动脉和皮下脂肪组织重建冠状动脉来治疗缺血性心肌病患者。

项目成果

Quercetin glucosides promote ischemia-induced angiogenesis, but do not promote tumor growth.

槲皮素葡萄糖苷促进缺血诱导的血管生成，但不促进肿瘤生长。

• DOI: 10.1016/j.lfs.2013.09.005
• 发表时间: 2013
• 期刊: Life Sciences.
• 作者: Sumi M;Tateishi N;Shibata H;Ohki T;Sata M.
• 通讯作者: Sata M.

RAA系と血管内皮機能・血管リモデリング

RAA系统与血管内皮功能/血管重塑

• 发表时间: 2013
• 期刊: Fluid Management Renaissance
• 作者: 福田大受;佐田政隆
• 通讯作者: 佐田政隆

Right ventricular systolic dysfunction in patients with exercise-induced pulmonary hypertension associated with connective tissue disease.

与结缔组织病相关的运动诱发肺动脉高压患者的右心室收缩功能障碍。

• 发表时间: 2014
• 作者: Saijo Y;Yamada H;Hotchi J;Nishio S;Hayashi S;Bando M;Hirata Y;Amano R;Ise T;Yagi S;Yamaguchi K;Iwase T;Soeki T;Wakatsuki T;Sata M.
• 通讯作者: Sata M.

Post-Transcriptional Regulation of Adiponectin by Micro-RNA 378 in Human Visceral and Subcutaneous Adipose Tissue.

人内脏和皮下脂肪组织中 Micro-RNA 378 对脂联素的转录后调节。

• 发表时间: 2013
• 作者: Ishida M;Shimabukuro M;Yagi S;Fukuda D;Soeki T;Sato H;Uematsu E;Izaki H;Kanayama H;Sata M.
• 通讯作者: Sata M.

Macrophage Toll-like Receptor 9 Signaling Contributes to the Development of Insulin Resistance through the Promotion of Inflammation in Adipose Tissue.

巨噬细胞 Toll 样受体 9 信号传导通过促进脂肪组织炎症而促进胰岛素抵抗的发展。

• 发表时间: 2013
• 作者: Nishimoto S;Fukuda D;Shimabukuro M;Yagi S;Soeki T;Sakaue H;Nakaya Y;Sata M.
• 通讯作者: Sata M.