| Project/Area Number |
16K15452
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Cardiovascular medicine
|
|---|
| Research Institution | National Cardiovascular Center Research Institute |
|---|
Principal Investigator |
SHIRAI Mikiyasu 国立研究開発法人国立循環器病研究センター, 研究所, 特任研究員 (70162758)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
土持 裕胤 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (60379948)
Pearson James 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (30261390)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
TO Seikon 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (90590646)
KIN Mika 国立研究開発法人国立循環器病研究センター, 研究所, 研究員 (40746773)
SEN Toun 国立研究開発法人国立循環器病研究センター, 研究所, 派遣研究員 (30616941)
INAGAKI Tadakatsu 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (20638366)
|
|---|
| Research Collaborator |
YAGI Naoto
|
|---|
| Project Period (FY) |
2016-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
|---|
| Keywords | 循環器・高血圧 / 糖尿病 / 心臓拡張機能障害 / 心筋収縮タンパク質 / 放射光X線回折法 / 心筋拡張機能障害 / 放射光Ｘ線回折法 |
|---|
| Outline of Final Research Achievements |
Applying our synchrotron radiation X-ray diffraction approach to the beating heart of the type 2 prediabetes Goto-Kakizaki (GK) rat, we found abnormal cardiac contractile protein dynamics in the subendocardium was associated with left ventricular diastolic dysfunction. GK rat hearts did not show altered phosphorylation state of the small myofilament proteins, but showed hypophosphorylation of titin. Myocardial soluble guanylate cyclase (sGC) protein expression and PKG activity were significantly depressed, and hypophosphorylation of titin correlated with depressed sGC-PKG activation. Synchrotron radiation microangiography enabled us to visualize the coronary circulation, which suggested that the GK rat does not have coronary endothelial dysfunction at this age, and therefore the previously hypothesised role of depressed endothelium dependent nitric oxide signaling driving diastolic dysfunction is not supported.
|
