Elucidation of molecular mechanisms regulating the gene expression of fetal cardiac ion channels and its implication as a novel therapeutic target for the treatment of heart failure

阐明调节胎儿心脏离子通道基因表达的分子机制及其作为心力衰竭治疗新靶点的意义

• 批准号: 20390224
• 负责人: KUWAHARA Koichiro
• 金额: $ 12.31万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390224/
• 关键词: イオンチャル; 心不全; 転写調節; 不整脈; イオンチャネル; イオンチヤンネル

Genetic remodeling contributes to the progression of pathological cardiac remodeling and heart failure by affecting myocardial cellular function and survival. In this study we evaluated the transcriptional regulation of fetal cardiac ion channels gene expression and the significance of these fetal ion channels as novel therapeutic targets for the treatment and prevention of heart failure. Our studies have revealed the transcriptional network regulating the expression of cardiac fetal-type ion channels, which are involved in the development of cardiac dysfunction and arrhythmias and potential therapeutic targets for the treatment and prevention of heart failure.

基因重塑通过影响心肌细胞功能和存活来促进病理性心脏重塑和心力衰竭的进展。在这项研究中，我们评估了胎儿心脏离子通道基因表达的转录调控以及这些胎儿离子通道作为治疗和预防心力衰竭的新治疗靶点的重要性。我们的研究揭示了调节心脏胎儿型离子通道表达的转录网络，这些离子通道参与心功能障碍和心律失常的发展，也是治疗和预防心力衰竭的潜在治疗靶点。

项目成果

The cardiac pacemaker-specific channel Hcn4 is a direct transcriptional target of MEF2

• DOI: 10.1093/cvr/cvp171
• 发表时间: 2009-09-01
• 期刊: CARDIOVASCULAR RESEARCH
• 影响因子: 10.8
• 作者: Kuratomi, Shinobu;Ohmori, Yoko;Takano, Makoto
• 通讯作者: Takano, Makoto

Transcriptional Pathways Regulating Caridac Remodeling.

调节Caridac重塑的转录途径。

• 发表时间: 2009
• 作者: Trapnell BC;Nakata K;Kavuru M.;西中村隆一;桑原宏一郎。
• 通讯作者: 桑原宏一郎。

p300 Plays a Critical Role in Maintaining Cardiac Mitochondrial Function and Cell Survival in Postnatal Hearts

• DOI: 10.1161/circresaha.109.206037
• 发表时间: 2009-10-09
• 期刊: CIRCULATION RESEARCH
• 影响因子: 20.1
• 作者: Nakagawa, Yasuaki;Kuwahara, Koichiro;Nakao, Kazuwa
• 通讯作者: Nakao, Kazuwa

Natriuretic Peptides-Guanylyl Cyclase-A Signaling Pathway Inhibits TRPC6-Mediated Pro-Hypertrophic Signaling in the Hearts

利钠肽-鸟苷基环化酶-A 信号通路抑制心脏中 TRPC6 介导的促肥大信号传导

• 发表时间: 2010
• 作者: Hideyuki Kinoshita;Satoru Usami;他11名
• 通讯作者: 他11名

Anovel NRSF-binding partner Zfp90 negatively regulates the repression activity of NRSF, a critical regulator of cardiac fetal gene program.

Anovel NRSF 结合伴侣 Zfp90 负向调节 NRSF 的抑制活性，NRSF 是心脏胎儿基因程序的关键调节因子。

• 发表时间: 2009
• 作者: Kuwahara K;Murakami M;Nakao K;et al.
• 通讯作者: et al.