Epac1 promotes neointimal thickening via calcium/calcineurin-dependent smooth muscle cell polarization and migration after vascular injury.
| Project/Area Number |
24790558
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Laboratory medicine
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
KATO Yuko 東京医科歯科大学, 大学院保健衛生学研究科, 助教 (50580875)
|
|---|
| Project Period (FY) |
2012-04-01 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 血管内膜肥厚 / Epac1 |
|---|
| Research Abstract |
Vascular remodeling after mechanoinjury largely depends on migration of aortic smooth muscle cell (ASMC). We have reported that activation of exchange protein activated by cAMP 1 (Epac1) promotes ASMC migration. However, the role of Epac1 in advancing vascular remodeling upon vascular injury in vivo, and the intracellular mechanisms remain unknown.
PDGF-BB-induced directional migration of Epac1KO ASMCs was significantly decreased. PDGF-BB-mediated intracellular Ca2+ elevation of Epac1KO ASMCs was significantly reduced. To assess the establishment of cell polarization under stimulation with PDGF-BB,activation of cofilin in Epac1KO ASMCs was significantly degreased. Activation of cofilin in WT ASMCs was suppressed by cyclosporine A, a calcineurin inhibitor. Ratio intimal thickening to smooth muscle layer of Epac1KO was significantly lower than that of WT.
These results suggest that Epac1 promotes directional migration of ASMC via calcium/calcineurin-mediated activation of cofilin.
|
Report
(3 results)
Research Products
(3 results)
