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.

缺血性心肌病唯一有效的治疗方法是心脏移植。然而，日本的捐赠者数量有限。因此，我们试图建立一种新的策略来替代心脏移植。对心脏搭桥手术期间获得的人动脉内膜切除术样本和心外膜脂肪的组织学分析表明，巨噬细胞和 T 细胞等炎症细胞不仅在血管壁中而且在血管周围脂肪组织中的浸润增强。我们还发现，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发挥着至关重要的作用。基于这些观察，我们开始开发一种新的手术策略，通过用外源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

Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein

Ghrelin 通过保留 connexin-43 蛋白来保护心脏免受缺血引起的心律失常

• DOI: 10.1007/s00380-013-0333-2
• 发表时间: 2013
• 期刊: Heart Vessels
• 影响因子: 1.5
• 作者: Soeki T;Niki T;Uematsu E;Bando S;Matsuura T;Kusunose K;Ise T;Ueda Y;Tomita N;Yamaguchi K;Koshiba K;Yagi S;Fukuda D;Taketani Y;Iwase T;Yamada H;Wakatsuki T;Akaike M;Shimabukuro M;Kishimoto I;Kangawa K;Sata M
• 通讯作者: Sata M

Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling.

• DOI: 10.1161/circulationaha.113.001533
• 发表时间: 2013-07-02
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Yoshida S;Aihara K;Ikeda Y;Sumitomo-Ueda Y;Uemoto R;Ishikawa K;Ise T;Yagi S;Iwase T;Mouri Y;Sakari M;Matsumoto T;Takeyama K;Akaike M;Matsumoto M;Sata M;Walsh K;Kato S;Matsumoto T
• 通讯作者: Matsumoto T

Spectacular migration of a central venous catherter into the pulmonary artery.

中心静脉导管壮观地迁移到肺动脉中。

• DOI: 10.1136/heartasia-2013-010287
• 发表时间: 2013
• 期刊: Heart Asia
• 作者: Tomoya Hara

Patent foramen ovale diagnosed by real-time three-dimensional contrast transesophageal echocardiography: A case report.

实时三维对比经食管超声心动图诊断卵圆孔未闭：一例报告。

• DOI: 10.1016/j.jccase.2012.10.011
• 发表时间: 2013
• 期刊: Journal of Cardiology Cases
• 作者: M. Shimabukuro;Y. Hirata;M. Tabata;M. Dagvasumberel;H. Sato;H. Kurobe;D. Fukuda;T. Soeki;T. Kitagawa;S. Takanashi;M. Sata;Noriko Tomita
• 通讯作者: Noriko Tomita

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.