Involvement of TRP channels in the cardiac hypertrophy and cell death

TRP 通道参与心脏肥大和细胞死亡

• 批准号: 22590801
• 负责人: ITO Hiroshi
• 金额: $ 2.75万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590801/
• 关键词: 心筋細胞肥大; 細胞死; Ca流入性TRPチャネル; STIM-1; Ｃａ流入性ＴＲＰチャネル; ＳＴＩＭ１; STIM1

In cardiac hypertrophy model, we could detect increases in the expression of TRPC1,-C3, -C6, brain natriuretic peptide (BNP), and NFAT activity, Ca entry, as well as increases in cell surface area. Gene silencing of the TRPC1 and pharmacological treatment with a pyrazole derivative or sildenafil attenuate the Ca entry and prevent cardiac hypertrophy. In analysis of stromal interaction molecule 1 (STIM1; known as a Ca sensor of intracellular Ca store) knockout mice, we provide evidence that STIM1 together with TRPC1 is crucial for the development of cardiac hypertrophy. Moreover, STIM1 contributes to cardiac fibrosis under the condition of pressure over load. Ultimately, TRPC/STIM1 system might become novel pharmacological target in the treatment of cardiac hypertrophy.

在心肌肥厚模型中，我们可以检测到TRPC 1，-C3，-C6，脑钠肽（BNP）的表达增加，NFAT活性增加，Ca内流增加，以及细胞表面积增加。TRPC 1的基因沉默和用吡唑衍生物或西地那非的药物治疗减弱Ca进入并防止心脏肥大。在分析基质相互作用分子1（STIM 1;被称为细胞内钙储存的钙传感器）敲除小鼠，我们提供的证据表明，STIM 1与TRPC 1一起是心脏肥大的发展至关重要。此外，在压力超负荷条件下，STIM 1有助于心脏纤维化。TRPC/STIM 1系统有望成为治疗心肌肥厚的新的药理学靶点。

项目成果

ＳＴＩＭ１ＫＯマウスにおける心肥大抑制効果

STIM1KO 小鼠心脏肥大抑制作用

• 作者: Nakano M;et. al.;大場貴喜
• 通讯作者: 大場貴喜

Transient Receptor Potential Channels as Novel Therapeutic Targets of Heart Failure

瞬时受体电位通道作为心力衰竭的新治疗靶点

• 发表时间: 2010
• 作者: Yoneda S;Oda K;Nasuno T;Nishino S;Kageyama M;Tokura M;Taguchi I;Abe S;Inoue T;Watanabe H
• 通讯作者: Watanabe H

Abnormal coagulation and platelet profile in patients with obstructive sleep apnea syndrome.

阻塞性睡眠呼吸暂停综合征患者的凝血和血小板特征异常。

• DOI: 10.1016/j.ijcard.2010.10.095
• 发表时间: 2011
• 期刊: International journal of cardiology
• 影响因子: 3.5
• 作者: Shigenori Terada;T. Koyama;Hiroyuki Watanabe;S. Makabe;G. Igarashi;Katsuhito Seki;Hiroshi Ito
• 通讯作者: Hiroshi Ito

Effect of short-duration adaptive servo-ventilation therapy on cardiac function in patients with heart failure.

• DOI: 10.1253/circj.cj-12-0328
• 发表时间: 2012
• 期刊: Circulation journal : official journal of the Japanese Circulation Society
• 作者: T. Koyama;Hiroyuki Watanabe;G. Igarashi;Y. Tamura;Ken Ikeda;Shigenori Terada;Hiroshi Ito

Ｓｔｒｏｍａｌ ｉｎｔｅｒａｃｔｉｏｎ ｍｏｌｅｃｕｌｅ １（ＳＴＩＭ１）ｍｅｄｉａｔｅｓ ＭＭＰ/ＴＩＭＰ Ｐａｔｈｗａｙ ｉｎ ｔｈｅ Ｃａｒｄｉａｃ Ｆｉｂｒｏｓｉｓ．

基质相互作用分子 1 (STIM1) 介导心脏纤维化中的 MMP/TIMP 通路。

• 作者: Tatebe S;Fukumoto Y;Sugimura K;Miura Y;Nochioka K;Aoki T;Yamamoto S;Wakayama M;Kagaya Y;Shimokawa H.;大場貴喜
• 通讯作者: 大場貴喜