| Item type |
文献 / Documents(1) |
| 公開日 |
2021-06-30 |
| 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/10.1016/j.vph.2019.106632 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1016/j.vph.2019.106632 |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| タイトル |
|
|
タイトル |
Thrombin inhibition by dabigatran attenuates endothelial dysfunction in diabetic mice |
|
言語 |
en |
| タイトル別表記 |
|
|
その他のタイトル |
Effects of dabigatran on diabetic endothelial dysfunction |
|
言語 |
en |
| 著者 |
Rahadian, Arief
福田, 大受
Salim, Hotimah Masdan
八木, 秀介
楠瀬, 賢也
山田, 博胤
添木, 武
島袋, 充生
佐田, 政隆
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Diabetic patients have coagulation abnormalities, in which thrombin plays a key role. Whereas accumulating evidence suggests that it also contributes to the development of vascular dysfunction through the activation of protease-activated receptors (PARs). Here we investigated whether the blockade of thrombin attenuates endothelial dysfunction in diabetic mice. Induction of diabetes by streptozotocin (STZ) increased the expression of PAR1, PAR3, and PAR4 in the aorta. STZ-induced diabetic mice showed impairment of endothelial function, while the administration of dabigatran etexilate, a direct thrombin inhibitor, significantly attenuated endothelial dysfunction in diabetic mice with no alteration of metabolic parameters including blood glucose level. Dabigatran did not affect endothelium-independent vasodilation. Dabigatran decreased the expression of inflammatory molecules (e.g., MCP-1 and ICAM-1) in the aorta of diabetic mice. Thrombin increased the expression of these inflammatory molecules and the phosphorylation of IκBα, and decreased the phosphorylation of eNOSSer1177 in human umbilical endothelial cells (HUVEC). Thrombin significantly impaired the endothelium-dependent vascular response of aortic rings obtained from wild-type mice. Inhibition of NF-κB attenuated thrombin-induced inflammatory molecule expression in HUVEC and ameliorated thrombin-induced endothelial dysfunction in aortic rings. Dabigatran attenuated the development of diabetes-induced endothelial dysfunction. Thrombin signaling may serve as a potential therapeutic target in diabetic condition. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Thrombin |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Endothelial function |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Dabigatran |
| 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 |
Diabetes |
| 書誌情報 |
en : Vascular Pharmacology
巻 124,
p. 106632,
発行日 2019-11-20
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| 収録物ID |
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|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
15371891 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA11703926 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12726778 |
| 出版者 |
|
|
出版者 |
Elsevier |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| EID |
|
|
識別子 |
360968 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
vph_124_106632.pdf (431 KB)
