| Item type |
文献 / Documents(1) |
| 公開日 |
2024-07-12 |
| 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.123.030084 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1161/JAHA.123.030084 |
| 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 |
Innate Immune System Regulated by Stimulator of Interferon Genes, a Cytosolic DNA Sensor, Regulates Endothelial Function |
|
言語 |
en |
| タイトル別表記 |
|
|
その他のタイトル |
STING and Endothelial Dysfunction |
|
言語 |
en |
| 著者 |
Pham, Phuong Tran
Bavuu, Oyunbileg
Kim-Kaneyama, Joo-Ri
Lei, Xiao-Feng
ヤマモト, タカユキ
オオツカ, ケンイチロウ
數藤, 久美子
楠瀬, 賢也
八木, 秀介
山田, 博胤
添木, 武
島袋, 充生
Barber, Glen N.
佐田, 政隆
福田, 大受
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
BACKGROUND: Sterile inflammation caused by metabolic disorders impairs endothelial function; however, the underlying mechanism by which hyperglycemia induces inflammation remains obscure. Recent studies have suggested that stimulator of interferon genes (STING), a key cytosolic DNA sensor in the innate immune system, contributes to the pathogenesis of inflammatory diseases. This study examines the role of the STING in endothelial dysfunction in streptozotocin-induced diabetic mice.
METHODS AND RESULTS: Injection of streptozotocin promoted the expression of STING and DNA damage markers in the aorta of wild-type mice. Streptozotocin elevated blood glucose and lipid levels in both wild-type and STING-deficient mice, which showed no statistical differences. Genetic deletion of STING ameliorated endothelial dysfunction as determined by the vascular relaxation in response to acetylcholine (P<0.001) and increased endothelial nitric oxide synthase phosphorylation in the aorta (P<0.05) in STZ-injected mice. Endothelium-independent vascular response to sodium nitroprusside did not differ. Treatment with a direct STING agonist, cyclic GMP-AMP, or mitochondrial DNA increased inflammatory molecule expression (eg, VCAM1 and IFNB) and decreased endothelial nitric oxide synthase phosphorylation in human umbilical vein endothelial cells, partially through the STING pathway. Cyclic GMP-AMP significantly impaired endothelial function of aortic segments obtained from wild-type mice, which was ameliorated in the presence of C-176, a STING inhibitor, or a neutralizing interferon-β antibody. Furthermore, the administration of C-176 ameliorated endothelial dysfunction in STZ-induced diabetic mice (P<0.01).
CONCLUSIONS: The DNA damage response regulated by STING impairs endothelial function. STING signaling may be a potential therapeutic target of endothelial dysfunction caused by hyperglycemia. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
diabetes |
| 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 |
nflammation |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
STING |
| 書誌情報 |
en : Journal of the American Heart Association
巻 12,
号 22,
p. e030084,
発行日 2023-11-10
|
| 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 |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
©2023 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-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. JAHA is available at: www.ahajournals.org/journal/jaha |
| EID |
|
|
識別子 |
404798 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
jaha_12_22_e030084.pdf (3.38 MB)
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