Research Projects to Clarify the Molecular Pathogenesis and to Develop Therapeutic or Preventive Strategy for Cardiomyopathy

阐明心肌病分子发病机制并制定治疗或预防策略的研究项目

• 批准号: 19390208
• 负责人: KIMURA Akinori
• 金额: $ 11.73万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390208/
• 关键词: 心筋症; 遺伝子変異; サルコメア; 筋収縮; カルシウム感受性; Z帯; CARP; ミオパラジン; ミオシン脱リン酸化酵素; M21; 原因遺伝子変異; Ca感受性; ミオシンフォスファターゼ; 性ホルモン; ZASP; Cypher; PP1M; トランスジェニックマウス; 網羅的発現解析; 結合ドメイン

In this research, we have identified CARP mutations as the molecular basis of cardiomyopathy. We also found PGM1 as a binding partner of ZASP and revealed that DCM-associated ZASP mutations impaired the binding to PGM1. In addition, PGM1 was found to be localized to Z-disc upon metabolic stress of cardiomyocytes. On the other hand, we reveled that M21 enhanced the phosphorylation of M110. Finally, we demonstrated that calcium sensitizer could prevent the pathological changes in the hearts of a model mice for dilated cardiomyopathy.

在这项研究中，我们已经确定CARP突变是心肌病的分子基础。我们还发现了PGM1作为ZASP的结合伴侣，并揭示了DCM相关的ZASP突变损害了与PGM1的结合。此外，发现心肌细胞代谢应激时，PGM1定位于Z盘。另一方面，我们发现M21增强了M110的磷酸化。最后，我们证明了钙增敏剂可以预防扩张型心肌病模型小鼠心脏的病理变化。

项目成果

Genome-wide association study to identify the disease-associated genes for coronary artery disease

全基因组关联研究，以确定冠状动脉疾病的疾病相关基因

• 发表时间: 2008
• 作者: Akimoto S;Miyasaka K.;山本直樹寺井崇二坂井田功;南野徹;寺井 崇二;Minamino T;Kimura A
• 通讯作者: Kimura A

Replication studies for the association of PSMA6 polymorphism with coronary artery disease in East Asian populations

• DOI: 10.1038/jhg.2009.22
• 发表时间: 2009-04-01
• 期刊: JOURNAL OF HUMAN GENETICS
• 影响因子: 3.5
• 作者: Hinohara, Kunihiko;Nakajima, Toshiaki;Kimura, Akinori
• 通讯作者: Kimura, Akinori

A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function.

• DOI: 10.1016/j.cell.2010.02.023
• 发表时间: 2010-04-02
• 期刊: Cell
• 影响因子: 64.5
• 作者: Neely GG;Kuba K;Cammarato A;Isobe K;Amann S;Zhang L;Murata M;Elmén L;Gupta V;Arora S;Sarangi R;Dan D;Fujisawa S;Usami T;Xia CP;Keene AC;Alayari NN;Yamakawa H;Elling U;Berger C;Novatchkova M;Koglgruber R;Fukuda K;Nishina H;Isobe M;Pospisilik JA;Imai Y;Pfeufer A;Hicks AA;Pramstaller PP;Subramaniam S;Kimura A;Ocorr K;Bodmer R;Penninger JM
• 通讯作者: Penninger JM

Molecular etiology of hypertrophic cardiomyopathy

肥厚型心肌病的分子病因学

• 发表时间: 2007
• 作者: Minamino T;Sano M;Komuro I;Kimura A
• 通讯作者: Kimura A

Replication of association between a chromosome 9p21 polymorphism with coronary artery disease in Japanese and Korean populations

日本和韩国人群中染色体 9p21 多态性与冠状动脉疾病之间关联的复制

• 发表时间: 2008
• 期刊: J Hum Genet (印刷中)
• 作者: Hinohara K;et. al.
• 通讯作者: et. al.