| Item type |
文献 / Documents(1) |
| 公開日 |
2019-04-11 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 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 |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1161/JAHA.118.010860 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1161/JAHA.118.010860 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Toll-Like Receptor 9 Plays a Pivotal Role in Angiotensin II–Induced Atherosclerosis |
|
言語 |
en |
| タイトル別表記 |
|
|
その他のタイトル |
Role of Toll-Like Receptor 9 in Atherogenesis |
|
言語 |
en |
| 著者 |
福田, 大受
ニシモト, サチコ
Aini, Kunduziayi
タナカ, アツシ
ニシグチ, ツヨシ
Kim-Kaneyama, Joo-ri
Lei, Xiao-Feng
増田, 清士
成戸, 卓也
タナカ, キミエ
ヒガシクニ, ヤストミ
ヒラタ, ヨウイチロウ
八木, 秀介
楠瀬, 賢也
山田, 博胤
添木, 武
井本, 逸勢
アカサカ, タカシ
島袋, 充生
佐田, 政隆
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Background
Toll-like receptor (TLR) 9 recognizes bacterial DNA, activating innate immunity, whereas it also provokes inflammation in response to fragmented DNA released from mammalian cells. We investigated whether TLR9 contributes to the development of vascular inflammation and atherogenesis using apolipoprotein E–deficient (Apoe-/-) mice.
Methods and Results
Tlr9-deficient Apoe-/- (Tlr9-/-Apoe-/-) mice and Apoe-/- mice on a Western-type diet received subcutaneous angiotensin II infusion (1000 ng/kg per minute) for 28 days. Angiotensin II increased the plasma level of double-stranded DNA, an endogenous ligand of TLR9, in these mice. Genetic deletion or pharmacologic blockade of TLR9 in angiotensin II–infused Apoe-/- mice attenuated atherogenesis in the aortic arch (P<0.05), reduced the accumulation of lipid and macrophages in atherosclerotic plaques, and decreased RNA expression of inflammatory molecules in the aorta with no alteration of metabolic parameters. On the other hand, restoration of TLR9 in bone marrow in Tlr9-/-Apoe-/- mice promoted atherogenesis in the aortic arch (P<0.05). A TLR9 agonist markedly promoted proinflammatory activation of Apoe-/- macrophages, partially through p38 mitogen-activated protein kinase signaling. In addition, genomic DNA extracted from macrophages promoted inflammatory molecule expression more effectively in Apoe-/- macrophages than in Tlr9-/-Apoe-/- macrophages. Furthermore, in humans, circulating double-stranded DNA in the coronary artery positively correlated with inflammatory features of coronary plaques determined by optical coherence tomography in patients with acute myocardial infarction (P<0.05).
Conclusions
TLR9 plays a pivotal role in the development of vascular inflammation and atherogenesis through proinflammatory activation of macrophages. TLR9 may serve as a potential therapeutic target for atherosclerosis. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
atherosclerosis |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
inflammation |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
macrophage |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Toll-like receptor 9 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
vascular inflammation |
| 書誌情報 |
en : Journal of the American Heart Association
巻 8,
号 7,
p. e010860,
発行日 2019-03-23
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20479980 |
| 出版者 |
|
|
出版者 |
The American Heart Association |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
Wiley |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
©2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| EID |
|
|
識別子 |
350365 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
jaha_8_7_e010860.pdf (2.75 MB)
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