Mechanism of atherosclerosis progression by platelet CLEC-2
| Project/Area Number |
18K06912
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 48040:Medical biochemistry-related
|
|---|
| Research Institution | University of Yamanashi |
|---|
Principal Investigator |
INOUE Osamu 山梨大学, 大学院総合研究部, 特任教授 (00432154)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
井上 克枝 山梨大学, 大学院総合研究部, 教授 (10324211)
築地 長治 山梨大学, 大学院総合研究部, 講師 (20710362)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 血小板 / CLEC-2 / podoplanin / 動脈硬化 / メカニズム |
|---|
| Outline of Final Research Achievements |
Platelets play a role in progression of atherosclerosis. Podoplanin, which is a ligand for a platelet activation receptor CLEC-2, is expressed on the surface of macrophages infiltrated into atherosclerotic lesion. CLEC-2 depletion inhibited atherosclerotic lesion and macrophage infiltration into the lesion in ApoE-deficient mice fed with high fat diet. These mice also showed increased percentage of monocytes in mononuclear cells and 20-50% of these monocytes bound to platelets. These findings suggest that platelet CLEC-2 binds to PDPN in monocytes, which facilitates monocyte infiltration into the subendothelial lesion and differentiation into macrophages, thereby atherosclerosis is aggravated.
|
| Academic Significance and Societal Importance of the Research Achievements |
動脈硬化病変は進行すると脂質に富むプラークとなるが、脆弱なため破綻した場合血栓症を引き起こす。血小板は、プラーク破綻時の血栓形成だけでなく動脈硬化自体の進行にも関与することが知られている。これまでにGPIbに代表されるいくつかの血小板活性化受容体の抗体やノックアウトマウスで動脈硬化進展抑制効果が確認されているが、出血傾向の助長という問題があった。血小板活性化受容体CLEC-2欠損マウスは、病的血栓形成は抑制されるが、出血傾向の有意な増悪は認められない。CLEC-2は、出血傾向のない抗動脈硬化薬剤のターゲット蛋白となりうる。
|
Report
(4 results)
Research Products
(12 results)
-
[Journal Article] Role of Platelet C-Type Lectin-Like Receptor 2 in Promoting Lung Metastasis in Osteosarcoma2020
Author(s)
Jiro Ichikawa, Takashi Ando, Tomonori Kawasaki, Tomoyuki Sasaki, Toshiaki Shirai, Nagaharu Tsukiji, Yujiro Kimura, Kaoru Aoki, Keiko Hayakawa, Katsue Suzuki-Inoue, Masao Saitoh, Hirotaka Haro
-
Journal Title
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume: in press
Issue: 9
Pages: 1738-1750
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
