Troponin T replacement can be a new therapy for dilated cardiomyopathy
| Project/Area Number |
16K15184
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
General physiology
|
|---|
| Research Institution | Jikei University School of Medicine |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
赤池 徹 東京慈恵会医科大学, 医学部, 講師 (20647101)
|
|---|
| Research Collaborator |
久我 和寛
藤本 義隆
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 心筋症 / 遺伝子治療 / 遺伝子異常 / 筋原線維 / トロポニン / 突然死 / 乳幼児 / 心不全 |
|---|
| Outline of Final Research Achievements |
The goal of this study is to develop a radical treatment for juvenile-onset dilated cardiomyopathy (DCM) with extremely poor prognosis. We hypothesized that "mutant troponin T can be replaced by overexpression of normal troponin T" and examined it using a juvenile onset DCM model mouse. We aimed to identify signaling molecules and regulatory mechanisms that act in progressive pathogenesis in children. In addition, structural and functional abnormalities of the myocardium in the very early stage of juvenile DCM mice were investigated, We found that the ΔK210-KI mouse is useful as a model for juvenile-onset DCM and is a good model for developing therapy for DCM. This study provided the fundamental basis for development of new DCM therapy.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究はトロポニン複合体を筋膜を温存した心筋細胞・組織においても置換可能であるという仮説を、実際の拡張型心筋症モデルを用いて検証する点に学術的特色がある。その検証の結果、ΔK210に由来する心筋細胞のカルシウム感受性低下を是正することが出来、心筋症の構造的・機能的異常を改善し得る可能性がある。また、若年型拡張型心筋症の極めて初期段階での異常を調べることによって、病態悪化に働くシグナル分子や調節機構を同定し、心移植に代わる新たな治療法の開発に繋がる。本研究は心移植が難しく、極めて予後不良である若年型拡張型心筋症への根本的治療法の開発につながり、臨床医学的にも意義深いと考える。
|
Report
(4 results)
Research Products
(31 results)
-
-
-
-
-
[Journal Article] Tissue thrombin is associated with the pathogenesis of dilated cardiomyopathy2017
Author(s)
Ito K, Hongo K, Date T, Ikegami M, Hano H, Owada M, Morimoto S, Kashiwagi Y, Katoh D, Yoshino T, Yoshii A, Kimura H, Nagoshi T, Kajimura I, Kusakari Y, Akaike T, Minamisawa S, Ogawa K, Minai K, Ogawa T, Kawai M, Yajima J, Matsuo S, Yamane T, Taniguchi I, Morimoto S, Yoshimura M.
-
Journal Title
Int J Cardiol
Volume: 228
Pages: 821-827
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] Nano-imaging of the beating mouse heart in vivo: importance of sarcomere dynamics, as opposed to sarcomere length per se, in the regulation of cardiac function.2016
Author(s)
Kobirumaki-Shimozawa F, Oyama K, Shimozawa T, Mizuno A, Ohki T, Terui T, Minamisawa S, Ishiwata S, Fukuda N
-
Journal Title
J. Gen. Physiol.
Volume: 147
Pages: 53-62
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
[Journal Article] Heterozygous deletion of Sarcolipin maintains normal cardiac function2016
Author(s)
Shimura D, Kusakari Y, Sasano T, Nakashima Y, Nakai G, Jiao Q, Jin M, Yokota T, Ishikawa Y, Nakano A, Goda N, Minamisawa S.
-
Journal Title
American Journal of Physiology - Heart and Circulatory Physiology
Volume: 310(1)
Pages: 92-103
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Low cardiac output leads hepatic fibrosis in right heart failure model rats2016
Author(s)
Fujimoto Y, Urashima T, Shimura D, Ito R, Kawachi S, Kajimura I, Akaike T, Kusakari Y, Fujiwara M, Ogawa K, Goda N, Ida H, Minamisawa S
-
Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
