2013 Fiscal Year Final Research Report
AMP-activated protein kinase in macrophage; its potential as a therapeutic target for atherosclerosis
| Project/Area Number |
24790930
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
ISHII Norio 熊本大学, 医学部附属病院, 助教 (10599111)
|
|---|
| Project Period (FY) |
2012-04-01 – 2014-03-31
|
| Keywords | マクロファージ / AMPK / 動脈硬化 / 細胞周期 |
|---|
| Research Abstract |
In this study, we investigated whether activation of AMP-activated protein kinase (AMPK) could suppress macrophage proliferation, using AICAR, which is a pharmacological AMPK activator. AMPK activation suppressed Ox-LDL-induced macrophage proliferation by suppressing GM-CSF expression and inducing cell cycle arrest. Moreover, treatment with AICAR suppressed atherosclerotic lesion formation, and decreased the number of PCNA-positive macrophages in apolipoprotein E-deficient mice. In conclusion, we found that AICAR-mediated AMPK activation suppressed Ox-LDL-induced macrophage proliferation by suppressing GM-CSF expression and inducing cell cycle arrest, and suppressed the progression of atherosclerosis in apolipoprotein E-deficient mice. Because the proliferation of vascular cells including macrophages is a key event in the development and progression of atherosclerosis, these effects of AMPK activation may represent therapeutic targets for atherosclerosis.
|
