| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2017-10-03 |
| タイトル |
|
|
タイトル |
Sphingosine-1-phosphate receptor-2 deficiency leads to inhibition of macrophage proinflammatory activities and atherosclerosis in apoE-deficient mice |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| ID登録 |
|
|
ID登録 |
10.24517/00014713 |
|
ID登録タイプ |
JaLC |
| 著者 |
Wang, Fei
Okamoto, Yasuo
Inoki, Isao
Yoshioka, Kazuaki
Du, Wa
Qi, Xun
Takuwa, Noriko
Gonda, Koichi
Yamamoto, Yasuhiko
Ohkawa, Ryunosuke
Nishiuchi, Takumi
Sugimoto, Naotoshi
Yatomi, Yutaka
Mitsumori, Kunitoshi
Asano, Masahide
Kinoshita, Makoto
Takuwa, Yoh
|
| 著者別表示 |
岡本, 安雄
吉岡, 和晃
多久和, 典子
山本, 靖彦
西内, 巧
杉本, 直俊
浅野, 雅秀
多久和, 陽
|
| 提供者所属 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
金沢大学医薬保健研究域医学系 |
| 書誌情報 |
The journal of clinical investigation
巻 120,
号 11,
p. 3979-3995,
発行日 2010-11-01
|
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0021-9738 |
| NCID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00695520 |
| DOI |
|
|
関連タイプ |
isIdenticalTo |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1172/JCI42315 |
| 出版者 |
|
|
出版者 |
American Society for Clinical Investigation |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid that has pleiotropic effects in a variety of cell types including ECs, SMCs, and macrophages, all of which are central to the development of atherosclerosis. It may therefore exert stimulatory and inhibitory effects on atherosclerosis. Here, we investigated the role of the S1P receptor S1PR2 in atherosclerosis by analyzing S1pr2–/– mice with an Apoe–/– background. S1PR2 was expressed in macrophages, ECs, and SMCs in atherosclerotic aortas. In S1pr2–/–Apoe–/– mice fed a high-cholesterol diet for 4 months, the area of the atherosclerotic plaque was markedly decreased, with reduced macrophage density, increased SMC density, increased eNOS phosphorylation, and downregulation of proinflammatory cytokines compared with S1pr2+/+Apoe–/– mice. Bone marrow chimera experiments indicated a major role for macrophage S1PR2 in atherogenesis. S1pr2–/–Apoe–/– macrophages showed diminished Rho/Rho kinase/NF-κB (ROCK/NF-κB) activity. Consequently, they also displayed reduced cytokine expression, reduced oxidized LDL uptake, and stimulated cholesterol efflux associated with decreased scavenger receptor expression and increased cholesterol efflux transporter expression. S1pr2–/–Apoe–/– ECs also showed reduced ROCK and NF-κB activities, with decreased MCP-1 expression and elevated eNOS phosphorylation. Pharmacologic S1PR2 blockade in S1pr2+/+Apoe–/– mice diminished the atherosclerotic plaque area in aortas and modified LDL accumulation in macrophages. We conclude therefore that S1PR2 plays a critical role in atherogenesis and may serve as a novel therapeutic target for atherosclerosis. |
| 権利 |
|
|
権利情報 |
Copyright © 2010, The American Society for Clinical Investigation |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 関連URI |
|
|
|
識別子タイプ |
URI |
|
|
関連識別子 |
http://www.jci.org/articles/view/42315 |
| 関連URI |
|
|
|
識別子タイプ |
URI |
|
|
関連識別子 |
http://www.jci.org |
ME-PR-TAKUWA-Y-3979.pdf (1.2 MB)
.png)
