| Project/Area Number |
23591077
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Hirosaki University |
|---|
Principal Investigator |
OKUMURA Ken 弘前大学, 医学(系)研究科(研究院), 教授 (20185549)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OSANAI Tomohiro 弘前大学, 大学院医学研究科, 准教授 (00169278)
|
|---|
| Project Period (FY) |
2011 – 2013
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
|---|
| Keywords | 循環器・高血圧 / 冠攣縮 / P122蛋白 / phospholipase C / R257H亜型PLC-δ1 / Phospholipase C / 冠孿縮 / phosphoｌipase C |
|---|
| Research Abstract |
We demonstrated that Phospholipase C(PLC)-d
1 activity in cultured skin fibroblasts from patients with coronary spastic angina(CSA) was enhanced, and found PLC-d1 864 G to A mutation in 10% of the male CSA patients. We also found p122 protein, cloned to potentiate PLC-d1 activity, and its gene expression level were enhanced in CSA. [Ca2+]i at baseline and the peak increase to acetylcholine were both higher in cells transfected with p122 than in those without p122. Further, we generated transgenic(TG) mice with the increased PLC-d1 activity specific to the VSMCs by inducing human R257H variant PLC-d1. Intravenous ergometrine induced ST segment elevation in homozygous TG. In isolated Langendorff-perfused hearts, coronary perfusion pressure was significantly increased in homozygous TG after ergometrine. Thus, the increased PLC-d1 activity causes the enhanced coronary vasomotility in TG. Both variant PLC-d1 and enhanced p122 protein were indicated to be involved in the pathogenesis of CSA.
|
